Neurology

We are all seeing more children on the autism spectrum than we ever expected. With a Centers for Disease Control–estimated prevalence of 1 in 44, the average pediatrician will be caring for 45 children with autism. It may feel like even more as parents bring in their children with related concerns or fears. Early entry into services has been shown to improve functioning, making early identification important. However, screening at the youngest ages has important limitations.

Sharing a concern about possible autism with parents is a painful aspect of primary care practice. We want to get it right, not frighten parents unnecessarily, nor miss children and delay intervention.

Autism screening is recommended by the American Academy of Pediatrics at 18- and 24-month pediatric well-child visits. There are several reasons for screening repeatedly: Autism symptoms emerge gradually in the toddler period; about 32% of children later found to have autism were developing in a typical pattern and appeared normal at 18 months only to regress by age 24 months; children may miss the 18 month screen; and all screens have false negatives as well as false positives. But even screening at these two ages is not enough.

One criticism of current screening tests pointed out by the U.S. Preventive Services Task Force has been a problem with the sample used to develop or validate the tool. Many test development studies included only children at risk by being in early intervention, siblings of children with diagnosed autism, or children only failing the screening tests rather than a community sample that the screen in actually used for.

Another obstacle to prediction of autism diagnoses made years later is that some children may not have had any clinical manifestations at the younger age even as judged by the best gold standard testing and, thus, negative screens were ambiguous. Additionally, data from prospective studies of high-risk infant siblings reveal that only 18% of children diagnosed with autism at 36 months were given that diagnosis at 18 months of age despite use of comprehensive diagnostic assessments.

Prevalence is also reported as 30% higher at age 8-12 years as at 3-7 years on gold-standard tests. Children identified later with autism tend to have milder symptoms and higher cognitive functioning. Therefore, we need some humility in thinking we can identify children as early as 18 months; rather, we need to use the best available methods at all ages and remain vigilant to symptoms as they evolve as well as to new screening and testing measures.

The most commonly used parent report screen is the 20-item Modified Checklist for Autism in Toddlers–Revised (M-CHAT-R), a modification of the original CHAT screen. To have reasonable positive predictive value, the M-CHAT-R authors recommend a clinician or trained staff member conduct a structured follow-up interview with the parent when the M-CHAT-R has a score of 3-7. Scores of 8 or more reflect enough symptoms to more strongly predict an autism diagnosis and thus the interview may be skipped in those cases. The recommended two-step process is called M-CHAT-R/F. At 18 months without the R/F, a positive M-CHAT-R only is associated with an autism diagnosis 27% of the time (PPV, 0.27); which is unacceptable for primary care use.

Unfortunately, the M-CHAT-R/F appears to be less accurate for 18-month-olds than 24-month-olds, in part because its yes/no response options are harder for a caregiver to answer, especially for behaviors just developing, or because of lack of experience with toddlers.

An alternative modification of the original CHAT called the Quantitative CHAT or Q-CHAT-10 has a range of response options for the caregiver; for example, always/usually/sometimes/rarely/never or many times a day/a few times a day/a few times a week/less than once a week/never. The authors of the Q-CHAT-10, however, recommend a summary pass/fail result for ease of use rather than using the range of response option values in the score. We recently published a study testing accuracy using add-up scoring that utilized the entire range of response option values, called Q-CHAT-10-O (O for ordinal), for children 16-20 months old as well as cartoon depictions of the behaviors. Our study also included diagnostic testing of screen-negative as well as screen-positive children to accurately calculate sensitivity and specificity for this method. In our study, Q-CHAT-10-O with a cutoff score greater than 11 showed higher sensitivity (0.63) than either M-CHAT-R/F (0.34) or Q-CHAT-10 (0.31) for this age range although the PPV (0.35) and negative predictive value (0.92) were comparable with M-CHAT R/F. Although Q-CHAT-10-O sensitivity (0.63) is less than M-CHAT-R (without follow-up; 0.73) and specificity (0.79) is less than the two-stage R/F procedure (0.90), on balance, it is more accurate and more practical for a primary care population. After 20 months of age, the M-CHAT-R/F has adequate accuracy to rescreen, if indicated, and for the subsequent 24 month screening. Language items are often of highest value in predicting outcomes in several tools including in the screen we are now validating for 18 month olds.

The Q-CHAT-10-O with ordinal scoring and pictures can also be recommended because it shows advantages over M-CHAT-R/F with half the number of items (10 vs. 20), no requirement for a follow-up interview, and improved sensitivity. Unlike M-CHAT-R, it also contributes to equity in screening because results did not differ depending on race or socioeconomic background.

Is there an even better way to detect autism in primary care? In 2022 an article was published regarding an exciting method of early autism detection called the Social Attention and Communication Surveillance–Revised (SACS-R), an eight-item observation checklist completed at public health nurse check-ups in Australia. The observers had 4 years of nursing degree education and a 3.5-hour training session.

The SACS-R and the preschool version (for older children) had significant associations with diagnostic testing at 12, 18, 24, and 42 months. The SACS-R had excellent PPV (82.6%), NPV (98.7%), and specificity (99.6%) and moderate sensitivity (61.5%) when used between 12 and 24 months of age. Pointing, eye contact, waving “bye, bye,” social communication by showing, and pretend play were the key indicators for observations at 18 months, with absence of three or more indicating risk for autism. Different key indicators were used at the other ages, reflecting the evolution of autism symptoms. This hybrid (observation and scoring) surveillance method by professionals shows hopeful data for the critical ability to identify children at risk for autism in primary care very early but requires more than parent report, that is, new levels of autism-specific clinician training and direct observations at multiple visits over time.

The takeaway is to remember that we should all watch closely for early signs of autism, informed by research on the key findings that a professional might observe, as well as by using the best screens available. We should remember that both false positives and false negatives are inherent in screening, especially at the youngest ages. We need to combine our concern with the parent’s concern as well as screen results and be sure to follow-up closely as symptoms can change in even a few months. Many factors may prevent a family from returning to see us or following our advice to go for testing or intervention, so tracking the child and their service use is an important part of the good care we strive to provide children with autism.

Other screening tools

You may have heard of other parent-report screens for autism. It is important to compare their accuracy specifically for 18-month-olds in a community setting.

• The Infant Toddler Checklist (https://psychology-tools.com/test/infant-toddler-checklist) has moderate overall psychometrics with sensitivity ranging from 0.55 to 0.77; specificity from 0.42 to 0.85; PPV from 0.20 to 0.55; and NPV from 0.83 to 0.94. However, the data were based on a sample including both community-dwelling toddlers and those with a family history of autism.
• The Brief Infant-Toddler Social and Emotional Assessment (https://eprovide.mapi-trust.org/instruments/brief-infant-toddler-social-emotional-assessment/) – the screen’s four autism-specific scales had high specificity (84%-90%) but low sensitivity (40%-52%).
• Canvas Dx (https://canvasdx.com/) from the Cognoa company is not a parent-report measure but rather a three-part evaluation including an app-based parent questionnaire, parent uploads of home videos analyzed by a specialist, and a 13- to 15-item primary care physician observational checklist. There were 56 diagnosed of the 426 children in the 18- to 24-month-old range from a sample of children presenting with parent or clinician concerns rather than from a community sample.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at pdnews@mdedge.com.

References

Sturner R et al. Autism screening at 18 months of age: A comparison of the Q-CHAT-10 and M-CHAT screeners. Molecular Autism. Jan 3;13(1):2.

Barbaro J et al. Diagnostic accuracy of the Social Attention and Communication Surveillance–Revised with preschool tool for early autism detection in very young children. JAMA Netw Open. 2022;5(3):e2146415.

We are all seeing more children on the autism spectrum than we ever expected. With a Centers for Disease Control–estimated prevalence of 1 in 44, the average pediatrician will be caring for 45 children with autism. It may feel like even more as parents bring in their children with related concerns or fears. Early entry into services has been shown to improve functioning, making early identification important. However, screening at the youngest ages has important limitations.

Sharing a concern about possible autism with parents is a painful aspect of primary care practice. We want to get it right, not frighten parents unnecessarily, nor miss children and delay intervention.

Autism screening is recommended by the American Academy of Pediatrics at 18- and 24-month pediatric well-child visits. There are several reasons for screening repeatedly: Autism symptoms emerge gradually in the toddler period; about 32% of children later found to have autism were developing in a typical pattern and appeared normal at 18 months only to regress by age 24 months; children may miss the 18 month screen; and all screens have false negatives as well as false positives. But even screening at these two ages is not enough.

One criticism of current screening tests pointed out by the U.S. Preventive Services Task Force has been a problem with the sample used to develop or validate the tool. Many test development studies included only children at risk by being in early intervention, siblings of children with diagnosed autism, or children only failing the screening tests rather than a community sample that the screen in actually used for.

Another obstacle to prediction of autism diagnoses made years later is that some children may not have had any clinical manifestations at the younger age even as judged by the best gold standard testing and, thus, negative screens were ambiguous. Additionally, data from prospective studies of high-risk infant siblings reveal that only 18% of children diagnosed with autism at 36 months were given that diagnosis at 18 months of age despite use of comprehensive diagnostic assessments.

Prevalence is also reported as 30% higher at age 8-12 years as at 3-7 years on gold-standard tests. Children identified later with autism tend to have milder symptoms and higher cognitive functioning. Therefore, we need some humility in thinking we can identify children as early as 18 months; rather, we need to use the best available methods at all ages and remain vigilant to symptoms as they evolve as well as to new screening and testing measures.

The most commonly used parent report screen is the 20-item Modified Checklist for Autism in Toddlers–Revised (M-CHAT-R), a modification of the original CHAT screen. To have reasonable positive predictive value, the M-CHAT-R authors recommend a clinician or trained staff member conduct a structured follow-up interview with the parent when the M-CHAT-R has a score of 3-7. Scores of 8 or more reflect enough symptoms to more strongly predict an autism diagnosis and thus the interview may be skipped in those cases. The recommended two-step process is called M-CHAT-R/F. At 18 months without the R/F, a positive M-CHAT-R only is associated with an autism diagnosis 27% of the time (PPV, 0.27); which is unacceptable for primary care use.

Unfortunately, the M-CHAT-R/F appears to be less accurate for 18-month-olds than 24-month-olds, in part because its yes/no response options are harder for a caregiver to answer, especially for behaviors just developing, or because of lack of experience with toddlers.

An alternative modification of the original CHAT called the Quantitative CHAT or Q-CHAT-10 has a range of response options for the caregiver; for example, always/usually/sometimes/rarely/never or many times a day/a few times a day/a few times a week/less than once a week/never. The authors of the Q-CHAT-10, however, recommend a summary pass/fail result for ease of use rather than using the range of response option values in the score. We recently published a study testing accuracy using add-up scoring that utilized the entire range of response option values, called Q-CHAT-10-O (O for ordinal), for children 16-20 months old as well as cartoon depictions of the behaviors. Our study also included diagnostic testing of screen-negative as well as screen-positive children to accurately calculate sensitivity and specificity for this method. In our study, Q-CHAT-10-O with a cutoff score greater than 11 showed higher sensitivity (0.63) than either M-CHAT-R/F (0.34) or Q-CHAT-10 (0.31) for this age range although the PPV (0.35) and negative predictive value (0.92) were comparable with M-CHAT R/F. Although Q-CHAT-10-O sensitivity (0.63) is less than M-CHAT-R (without follow-up; 0.73) and specificity (0.79) is less than the two-stage R/F procedure (0.90), on balance, it is more accurate and more practical for a primary care population. After 20 months of age, the M-CHAT-R/F has adequate accuracy to rescreen, if indicated, and for the subsequent 24 month screening. Language items are often of highest value in predicting outcomes in several tools including in the screen we are now validating for 18 month olds.

The Q-CHAT-10-O with ordinal scoring and pictures can also be recommended because it shows advantages over M-CHAT-R/F with half the number of items (10 vs. 20), no requirement for a follow-up interview, and improved sensitivity. Unlike M-CHAT-R, it also contributes to equity in screening because results did not differ depending on race or socioeconomic background.

Is there an even better way to detect autism in primary care? In 2022 an article was published regarding an exciting method of early autism detection called the Social Attention and Communication Surveillance–Revised (SACS-R), an eight-item observation checklist completed at public health nurse check-ups in Australia. The observers had 4 years of nursing degree education and a 3.5-hour training session.

The SACS-R and the preschool version (for older children) had significant associations with diagnostic testing at 12, 18, 24, and 42 months. The SACS-R had excellent PPV (82.6%), NPV (98.7%), and specificity (99.6%) and moderate sensitivity (61.5%) when used between 12 and 24 months of age. Pointing, eye contact, waving “bye, bye,” social communication by showing, and pretend play were the key indicators for observations at 18 months, with absence of three or more indicating risk for autism. Different key indicators were used at the other ages, reflecting the evolution of autism symptoms. This hybrid (observation and scoring) surveillance method by professionals shows hopeful data for the critical ability to identify children at risk for autism in primary care very early but requires more than parent report, that is, new levels of autism-specific clinician training and direct observations at multiple visits over time.

The takeaway is to remember that we should all watch closely for early signs of autism, informed by research on the key findings that a professional might observe, as well as by using the best screens available. We should remember that both false positives and false negatives are inherent in screening, especially at the youngest ages. We need to combine our concern with the parent’s concern as well as screen results and be sure to follow-up closely as symptoms can change in even a few months. Many factors may prevent a family from returning to see us or following our advice to go for testing or intervention, so tracking the child and their service use is an important part of the good care we strive to provide children with autism.

Other screening tools

You may have heard of other parent-report screens for autism. It is important to compare their accuracy specifically for 18-month-olds in a community setting.

• The Infant Toddler Checklist (https://psychology-tools.com/test/infant-toddler-checklist) has moderate overall psychometrics with sensitivity ranging from 0.55 to 0.77; specificity from 0.42 to 0.85; PPV from 0.20 to 0.55; and NPV from 0.83 to 0.94. However, the data were based on a sample including both community-dwelling toddlers and those with a family history of autism.
• The Brief Infant-Toddler Social and Emotional Assessment (https://eprovide.mapi-trust.org/instruments/brief-infant-toddler-social-emotional-assessment/) – the screen’s four autism-specific scales had high specificity (84%-90%) but low sensitivity (40%-52%).
• Canvas Dx (https://canvasdx.com/) from the Cognoa company is not a parent-report measure but rather a three-part evaluation including an app-based parent questionnaire, parent uploads of home videos analyzed by a specialist, and a 13- to 15-item primary care physician observational checklist. There were 56 diagnosed of the 426 children in the 18- to 24-month-old range from a sample of children presenting with parent or clinician concerns rather than from a community sample.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at pdnews@mdedge.com.

References

Sturner R et al. Autism screening at 18 months of age: A comparison of the Q-CHAT-10 and M-CHAT screeners. Molecular Autism. Jan 3;13(1):2.

Barbaro J et al. Diagnostic accuracy of the Social Attention and Communication Surveillance–Revised with preschool tool for early autism detection in very young children. JAMA Netw Open. 2022;5(3):e2146415.

We are all seeing more children on the autism spectrum than we ever expected. With a Centers for Disease Control–estimated prevalence of 1 in 44, the average pediatrician will be caring for 45 children with autism. It may feel like even more as parents bring in their children with related concerns or fears. Early entry into services has been shown to improve functioning, making early identification important. However, screening at the youngest ages has important limitations.

Sharing a concern about possible autism with parents is a painful aspect of primary care practice. We want to get it right, not frighten parents unnecessarily, nor miss children and delay intervention.

Autism screening is recommended by the American Academy of Pediatrics at 18- and 24-month pediatric well-child visits. There are several reasons for screening repeatedly: Autism symptoms emerge gradually in the toddler period; about 32% of children later found to have autism were developing in a typical pattern and appeared normal at 18 months only to regress by age 24 months; children may miss the 18 month screen; and all screens have false negatives as well as false positives. But even screening at these two ages is not enough.

One criticism of current screening tests pointed out by the U.S. Preventive Services Task Force has been a problem with the sample used to develop or validate the tool. Many test development studies included only children at risk by being in early intervention, siblings of children with diagnosed autism, or children only failing the screening tests rather than a community sample that the screen in actually used for.

Another obstacle to prediction of autism diagnoses made years later is that some children may not have had any clinical manifestations at the younger age even as judged by the best gold standard testing and, thus, negative screens were ambiguous. Additionally, data from prospective studies of high-risk infant siblings reveal that only 18% of children diagnosed with autism at 36 months were given that diagnosis at 18 months of age despite use of comprehensive diagnostic assessments.

Prevalence is also reported as 30% higher at age 8-12 years as at 3-7 years on gold-standard tests. Children identified later with autism tend to have milder symptoms and higher cognitive functioning. Therefore, we need some humility in thinking we can identify children as early as 18 months; rather, we need to use the best available methods at all ages and remain vigilant to symptoms as they evolve as well as to new screening and testing measures.

The most commonly used parent report screen is the 20-item Modified Checklist for Autism in Toddlers–Revised (M-CHAT-R), a modification of the original CHAT screen. To have reasonable positive predictive value, the M-CHAT-R authors recommend a clinician or trained staff member conduct a structured follow-up interview with the parent when the M-CHAT-R has a score of 3-7. Scores of 8 or more reflect enough symptoms to more strongly predict an autism diagnosis and thus the interview may be skipped in those cases. The recommended two-step process is called M-CHAT-R/F. At 18 months without the R/F, a positive M-CHAT-R only is associated with an autism diagnosis 27% of the time (PPV, 0.27); which is unacceptable for primary care use.

Unfortunately, the M-CHAT-R/F appears to be less accurate for 18-month-olds than 24-month-olds, in part because its yes/no response options are harder for a caregiver to answer, especially for behaviors just developing, or because of lack of experience with toddlers.

An alternative modification of the original CHAT called the Quantitative CHAT or Q-CHAT-10 has a range of response options for the caregiver; for example, always/usually/sometimes/rarely/never or many times a day/a few times a day/a few times a week/less than once a week/never. The authors of the Q-CHAT-10, however, recommend a summary pass/fail result for ease of use rather than using the range of response option values in the score. We recently published a study testing accuracy using add-up scoring that utilized the entire range of response option values, called Q-CHAT-10-O (O for ordinal), for children 16-20 months old as well as cartoon depictions of the behaviors. Our study also included diagnostic testing of screen-negative as well as screen-positive children to accurately calculate sensitivity and specificity for this method. In our study, Q-CHAT-10-O with a cutoff score greater than 11 showed higher sensitivity (0.63) than either M-CHAT-R/F (0.34) or Q-CHAT-10 (0.31) for this age range although the PPV (0.35) and negative predictive value (0.92) were comparable with M-CHAT R/F. Although Q-CHAT-10-O sensitivity (0.63) is less than M-CHAT-R (without follow-up; 0.73) and specificity (0.79) is less than the two-stage R/F procedure (0.90), on balance, it is more accurate and more practical for a primary care population. After 20 months of age, the M-CHAT-R/F has adequate accuracy to rescreen, if indicated, and for the subsequent 24 month screening. Language items are often of highest value in predicting outcomes in several tools including in the screen we are now validating for 18 month olds.

The Q-CHAT-10-O with ordinal scoring and pictures can also be recommended because it shows advantages over M-CHAT-R/F with half the number of items (10 vs. 20), no requirement for a follow-up interview, and improved sensitivity. Unlike M-CHAT-R, it also contributes to equity in screening because results did not differ depending on race or socioeconomic background.

Is there an even better way to detect autism in primary care? In 2022 an article was published regarding an exciting method of early autism detection called the Social Attention and Communication Surveillance–Revised (SACS-R), an eight-item observation checklist completed at public health nurse check-ups in Australia. The observers had 4 years of nursing degree education and a 3.5-hour training session.

The SACS-R and the preschool version (for older children) had significant associations with diagnostic testing at 12, 18, 24, and 42 months. The SACS-R had excellent PPV (82.6%), NPV (98.7%), and specificity (99.6%) and moderate sensitivity (61.5%) when used between 12 and 24 months of age. Pointing, eye contact, waving “bye, bye,” social communication by showing, and pretend play were the key indicators for observations at 18 months, with absence of three or more indicating risk for autism. Different key indicators were used at the other ages, reflecting the evolution of autism symptoms. This hybrid (observation and scoring) surveillance method by professionals shows hopeful data for the critical ability to identify children at risk for autism in primary care very early but requires more than parent report, that is, new levels of autism-specific clinician training and direct observations at multiple visits over time.

The takeaway is to remember that we should all watch closely for early signs of autism, informed by research on the key findings that a professional might observe, as well as by using the best screens available. We should remember that both false positives and false negatives are inherent in screening, especially at the youngest ages. We need to combine our concern with the parent’s concern as well as screen results and be sure to follow-up closely as symptoms can change in even a few months. Many factors may prevent a family from returning to see us or following our advice to go for testing or intervention, so tracking the child and their service use is an important part of the good care we strive to provide children with autism.

Other screening tools

You may have heard of other parent-report screens for autism. It is important to compare their accuracy specifically for 18-month-olds in a community setting.

• The Infant Toddler Checklist (https://psychology-tools.com/test/infant-toddler-checklist) has moderate overall psychometrics with sensitivity ranging from 0.55 to 0.77; specificity from 0.42 to 0.85; PPV from 0.20 to 0.55; and NPV from 0.83 to 0.94. However, the data were based on a sample including both community-dwelling toddlers and those with a family history of autism.
• The Brief Infant-Toddler Social and Emotional Assessment (https://eprovide.mapi-trust.org/instruments/brief-infant-toddler-social-emotional-assessment/) – the screen’s four autism-specific scales had high specificity (84%-90%) but low sensitivity (40%-52%).
• Canvas Dx (https://canvasdx.com/) from the Cognoa company is not a parent-report measure but rather a three-part evaluation including an app-based parent questionnaire, parent uploads of home videos analyzed by a specialist, and a 13- to 15-item primary care physician observational checklist. There were 56 diagnosed of the 426 children in the 18- to 24-month-old range from a sample of children presenting with parent or clinician concerns rather than from a community sample.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at pdnews@mdedge.com.

References

Sturner R et al. Autism screening at 18 months of age: A comparison of the Q-CHAT-10 and M-CHAT screeners. Molecular Autism. Jan 3;13(1):2.

Barbaro J et al. Diagnostic accuracy of the Social Attention and Communication Surveillance–Revised with preschool tool for early autism detection in very young children. JAMA Netw Open. 2022;5(3):e2146415.

NASHVILLE, TENN. – Patients with dementia and active seizures experience faster cognitive and functional decline and have a greater risk of dying younger than people with dementia who don’t have seizures, according to a multicenter study presented at the 2022 annual meeting of the American Epilepsy Society.

“When we compared patients with seizures with those who did not have seizures, we found that patients with seizures were more likely to have more severe cognitive impairment; they were more likely to have physical dependence and so worse functional outcomes; and they also had higher mortality rates at a younger age,” lead study author Ifrah Zawar, MD, an assistant professor of neurology at the University of Virginia, Charlottesville, said in an interview.

“The average age of mortality for seizure patients was around 72 years and the average age of mortality for nonseizure patients was around 79 years, so there was a 7- to 8-year difference in mortality,” she said.
 

Seizures make matters worse

The study analyzed data on 26,425 patients with dementia, 374 (1.4%) of whom had seizures, collected from 2005 to 2021 at 39 Alzheimer’s disease centers in the United States. Patients who had seizures were significantly younger when cognitive decline began (ages 62.9 vs. 68.4 years, P < .001) and died younger (72.99 vs. 79.72 years, P < .001).

The study also found a number of factors associated with active seizures, including a history of dominant Alzheimer’s disease mutation (odds ratio, 5.55; P < .001), stroke (OR, 3.17; P < .001), transient ischemic attack (OR, 1.72; P = .003), traumatic brain injury (OR, 1.92; P < .001), Parkinson’s disease (OR, 1.79; P = .025), active depression (OR, 1.61; P < .001) and lower education (OR, 0.97; P =.043).

After the study made adjustments for sex and other associated factors, it found that patients with seizures were still at a 76% higher risk of dying younger (hazard ratio, 1.76; P < .001).

The study also determined that patients with seizures had worse functional assessment scores and were more likely to be physically dependent on others (OR, 2.52; P < .001). Seizure patients also performed worse on Mini-Mental Status Examination (18.50 vs. 22.88; P < .001) and Clinical Dementia Rating-Sum of boxes (7.95 vs. 4.28; P < .001) after adjusting for age and duration of cognitive decline.
 

A tip for caregivers

Dr. Zawar acknowledged that differentiating seizures from transient bouts of confusion in people with dementia can be difficult for family members and caregivers, but she offered advice to help them do so. “If they notice any unusual confusion or any altered mentation which is episodic in nature,” she said, “they should bring it to the neurologist’s attention as early as possible, because there are studies that have shown the diagnosis of seizures is delayed, and if they are treated in time they can be well-controlled.” Electroencephalography can also confirm the presence of seizures, she added.

Double whammy

One limitation of this study is the lack of details on the types of seizures the participants had along with the inconsistency of EEGs performed on the study population. “In future studies, I would like to have more EEG data on the types of seizures and the frequency of seizures to assess these factors further,” Dr. Zawar said.

Having more detailed information on the seizures would make the findings more valuable, Andrew J. Cole, MD, director of the epilepsy service at Massachusetts General Hospital in Boston said in an interview. “We know a lot about clinically apparent seizures, as witnessed by this paper, but we still don’t know a whole lot about clinically silent or cryptic or nighttime-only seizures that maybe no one would really recognize as such unless they were specifically looking for them, and this paper doesn’t address that issue,” he said.

While the finding that patients with other neurologic diseases have more seizures even if they also have Alzheimer’s disease isn’t “a huge surprise,” Dr. Cole added. “On the other hand, the paper is important because it shows us that in the course of having Alzheimer’s disease, having seizures also makes your outcome worse, the speed of progression faster, and it complicates the management and living with this disease, and they make that point quite clear.”

Dr. Zawar and Dr. Cole have no relevant disclosures.
 

NASHVILLE, TENN. – Patients with dementia and active seizures experience faster cognitive and functional decline and have a greater risk of dying younger than people with dementia who don’t have seizures, according to a multicenter study presented at the 2022 annual meeting of the American Epilepsy Society.

“When we compared patients with seizures with those who did not have seizures, we found that patients with seizures were more likely to have more severe cognitive impairment; they were more likely to have physical dependence and so worse functional outcomes; and they also had higher mortality rates at a younger age,” lead study author Ifrah Zawar, MD, an assistant professor of neurology at the University of Virginia, Charlottesville, said in an interview.

“The average age of mortality for seizure patients was around 72 years and the average age of mortality for nonseizure patients was around 79 years, so there was a 7- to 8-year difference in mortality,” she said.
 

Seizures make matters worse

The study analyzed data on 26,425 patients with dementia, 374 (1.4%) of whom had seizures, collected from 2005 to 2021 at 39 Alzheimer’s disease centers in the United States. Patients who had seizures were significantly younger when cognitive decline began (ages 62.9 vs. 68.4 years, P < .001) and died younger (72.99 vs. 79.72 years, P < .001).

The study also found a number of factors associated with active seizures, including a history of dominant Alzheimer’s disease mutation (odds ratio, 5.55; P < .001), stroke (OR, 3.17; P < .001), transient ischemic attack (OR, 1.72; P = .003), traumatic brain injury (OR, 1.92; P < .001), Parkinson’s disease (OR, 1.79; P = .025), active depression (OR, 1.61; P < .001) and lower education (OR, 0.97; P =.043).

After the study made adjustments for sex and other associated factors, it found that patients with seizures were still at a 76% higher risk of dying younger (hazard ratio, 1.76; P < .001).

The study also determined that patients with seizures had worse functional assessment scores and were more likely to be physically dependent on others (OR, 2.52; P < .001). Seizure patients also performed worse on Mini-Mental Status Examination (18.50 vs. 22.88; P < .001) and Clinical Dementia Rating-Sum of boxes (7.95 vs. 4.28; P < .001) after adjusting for age and duration of cognitive decline.
 

A tip for caregivers

Dr. Zawar acknowledged that differentiating seizures from transient bouts of confusion in people with dementia can be difficult for family members and caregivers, but she offered advice to help them do so. “If they notice any unusual confusion or any altered mentation which is episodic in nature,” she said, “they should bring it to the neurologist’s attention as early as possible, because there are studies that have shown the diagnosis of seizures is delayed, and if they are treated in time they can be well-controlled.” Electroencephalography can also confirm the presence of seizures, she added.

Double whammy

One limitation of this study is the lack of details on the types of seizures the participants had along with the inconsistency of EEGs performed on the study population. “In future studies, I would like to have more EEG data on the types of seizures and the frequency of seizures to assess these factors further,” Dr. Zawar said.

Having more detailed information on the seizures would make the findings more valuable, Andrew J. Cole, MD, director of the epilepsy service at Massachusetts General Hospital in Boston said in an interview. “We know a lot about clinically apparent seizures, as witnessed by this paper, but we still don’t know a whole lot about clinically silent or cryptic or nighttime-only seizures that maybe no one would really recognize as such unless they were specifically looking for them, and this paper doesn’t address that issue,” he said.

While the finding that patients with other neurologic diseases have more seizures even if they also have Alzheimer’s disease isn’t “a huge surprise,” Dr. Cole added. “On the other hand, the paper is important because it shows us that in the course of having Alzheimer’s disease, having seizures also makes your outcome worse, the speed of progression faster, and it complicates the management and living with this disease, and they make that point quite clear.”

Dr. Zawar and Dr. Cole have no relevant disclosures.
 

NASHVILLE, TENN. – Patients with dementia and active seizures experience faster cognitive and functional decline and have a greater risk of dying younger than people with dementia who don’t have seizures, according to a multicenter study presented at the 2022 annual meeting of the American Epilepsy Society.

“When we compared patients with seizures with those who did not have seizures, we found that patients with seizures were more likely to have more severe cognitive impairment; they were more likely to have physical dependence and so worse functional outcomes; and they also had higher mortality rates at a younger age,” lead study author Ifrah Zawar, MD, an assistant professor of neurology at the University of Virginia, Charlottesville, said in an interview.

“The average age of mortality for seizure patients was around 72 years and the average age of mortality for nonseizure patients was around 79 years, so there was a 7- to 8-year difference in mortality,” she said.
 

Seizures make matters worse

The study analyzed data on 26,425 patients with dementia, 374 (1.4%) of whom had seizures, collected from 2005 to 2021 at 39 Alzheimer’s disease centers in the United States. Patients who had seizures were significantly younger when cognitive decline began (ages 62.9 vs. 68.4 years, P < .001) and died younger (72.99 vs. 79.72 years, P < .001).

The study also found a number of factors associated with active seizures, including a history of dominant Alzheimer’s disease mutation (odds ratio, 5.55; P < .001), stroke (OR, 3.17; P < .001), transient ischemic attack (OR, 1.72; P = .003), traumatic brain injury (OR, 1.92; P < .001), Parkinson’s disease (OR, 1.79; P = .025), active depression (OR, 1.61; P < .001) and lower education (OR, 0.97; P =.043).

After the study made adjustments for sex and other associated factors, it found that patients with seizures were still at a 76% higher risk of dying younger (hazard ratio, 1.76; P < .001).

The study also determined that patients with seizures had worse functional assessment scores and were more likely to be physically dependent on others (OR, 2.52; P < .001). Seizure patients also performed worse on Mini-Mental Status Examination (18.50 vs. 22.88; P < .001) and Clinical Dementia Rating-Sum of boxes (7.95 vs. 4.28; P < .001) after adjusting for age and duration of cognitive decline.
 

A tip for caregivers

Dr. Zawar acknowledged that differentiating seizures from transient bouts of confusion in people with dementia can be difficult for family members and caregivers, but she offered advice to help them do so. “If they notice any unusual confusion or any altered mentation which is episodic in nature,” she said, “they should bring it to the neurologist’s attention as early as possible, because there are studies that have shown the diagnosis of seizures is delayed, and if they are treated in time they can be well-controlled.” Electroencephalography can also confirm the presence of seizures, she added.

Double whammy

One limitation of this study is the lack of details on the types of seizures the participants had along with the inconsistency of EEGs performed on the study population. “In future studies, I would like to have more EEG data on the types of seizures and the frequency of seizures to assess these factors further,” Dr. Zawar said.

Having more detailed information on the seizures would make the findings more valuable, Andrew J. Cole, MD, director of the epilepsy service at Massachusetts General Hospital in Boston said in an interview. “We know a lot about clinically apparent seizures, as witnessed by this paper, but we still don’t know a whole lot about clinically silent or cryptic or nighttime-only seizures that maybe no one would really recognize as such unless they were specifically looking for them, and this paper doesn’t address that issue,” he said.

While the finding that patients with other neurologic diseases have more seizures even if they also have Alzheimer’s disease isn’t “a huge surprise,” Dr. Cole added. “On the other hand, the paper is important because it shows us that in the course of having Alzheimer’s disease, having seizures also makes your outcome worse, the speed of progression faster, and it complicates the management and living with this disease, and they make that point quite clear.”

Dr. Zawar and Dr. Cole have no relevant disclosures.
 

NASHVILLE, TENN. – About 21% of teens newly diagnosed with epilepsy experience suicidal ideation, and the percentage jumps to 31% within 3 years, new research reveals.

“We hope these results inspire epileptologists and neurologists to both recognize and screen for suicide ideation and behaviors in their adolescent patients,” said study investigator Hadley Greenwood, a third-year medical student at New York University.

The new data should also encourage providers “to become more comfortable” providing support to patients, “be that by increasing their familiarity with prescribing different antidepressants or by being well versed in how to connect patients to resources within their community,” said Mr. Greenwood.

The findings were presented here at the annual meeting of the American Epilepsy Society.
 

Little research

Previous studies have reported on the prevalence of suicidality as well as depression and anxiety among adults with epilepsy. “We wanted to look at adolescents because there’s much less in the literature out there about psychiatric comorbidity, and specifically suicidality, in this population,” said Mr. Greenwood.

Researchers used data from the Human Epilepsy Project, a study that collected data from 34 sites in the United States, Canada, Europe, and Australia from 2012 to 2017.

From a cohort of more than 400 participants, researchers identified 67 patients aged 11-17 years who were enrolled within 4 months of starting treatment for focal epilepsy.

Participants completed the Columbia–Suicide Severity Rating Scale (C-SSRS) at enrollment and at follow-ups over 36 months. The C-SSRS measures suicidal ideation and severity, said Mr. Greenwood.

“It’s scaled from passive suicide ideation, such as thoughts of ‘I wish I were dead’ without active intent, all the way up to active suicidal ideation with a plan and intent.”

Researchers were able to distinguish individuals with passive suicide ideation from those with more serious intentions, said Mr. Greenwood. They used medical records to evaluate the prevalence of suicidal ideation and behavior.

The investigators found that more than one in five (20.9%) teens endorsed any lifetime suicide ideation. This, said Mr. Greenwood, is “roughly equivalent” to the prevalence reported earlier in the adult cohort of the Human Epilepsy Project (21.6%).
 

‘Striking’ rate

The fact that one in five adolescents had any lifetime suicide ideation is “definitely a striking number,” said Mr. Greenwood.

Researchers found that 15% of patients experienced active suicide ideation, 7.5% exhibited preparatory or suicidal behaviors, and 3% had made a prior suicide attempt.

All of these percentages increased at 3 years: Thirty-one percent for suicide ideation; 25% for active suicide behavior, 15% for preparatory or suicide behaviors, and 5% for prior suicide attempt.

The fact that nearly one in three adolescents endorsed suicide ideation at 3 years is another “striking” finding, said Mr. Greenwood.

Of the 53 adolescents who had never had suicide ideation at the time of enrollment, 7 endorsed new-onset suicide ideation in the follow-up period. Five of 14 who had had suicide ideation at some point prior to enrollment continued to endorse it.

“The value of the study is identifying the prevalence and identifying the significant number of adolescents with epilepsy who are endorsing either suicide ideation or suicidal behaviors,” said Mr. Greenwood.

The researchers found that among younger teens (aged 11–14 years) rates of suicide ideation were higher than among their older counterparts (aged 15–17 years).

The study does not shed light on the biological connection between epilepsy and suicidality, but Mr. Greenwood noted that prior research has suggested a bidirectional relationship.

“Depression and other psychiatric comorbidities might exist prior to epileptic activity and actually predispose to epileptic activity.”

Mr. Greenwood noted that suicide ideation has “spiked” recently across the general population, and so it’s difficult to compare the prevalence in her study with “today’s prevalence.”

However, other research generally shows that the suicide ideation rate in the general adolescent population is much lower than in teens with epilepsy.

Unique aspects of the current study are that it reports suicide ideation and behaviors at around the time of an epilepsy diagnosis and documents how suicidality progresses or resolves over time, said Mr. Greenwood.
 

Underdiagnosed, undertreated

Commenting on the research, Elizabeth Donner, MD, director of the comprehensive epilepsy program, Hospital for Sick Children, and associate professor, department of pediatrics, University of Toronto, said a “key point” from the study is that the suicidality rate among teens with epilepsy exceeds that of children not living with epilepsy.

“We are significantly underdiagnosing and undertreating the mental health comorbidities in epilepsy,” said Dr. Donner. “Epilepsy is a brain disease and so are mental health disorders, so it shouldn’t come as any surprise that they coexist in individuals with epilepsy.”

The new results contribute to what is already known about the significant mortality rates among persons with epilepsy, said Dr. Donner. She referred to a 2018 study that showed that people with epilepsy were 3.5 times more likely to die by suicide.

Other research has shown that people with epilepsy are 10 times more likely to die by drowning, mostly in the bathtub, said Dr. Donner.

“You would think that we’re educating these people about risks related to their epilepsy, but either the messages don’t get through, or they don’t know how to keep themselves safe,” she said.

“This needs to be seen in a bigger picture, and the bigger picture is we need to recognize comorbid mental health issues; we need to address them once recognized; and then we need to counsel and support people to live safely with their epilepsy.

The study received funding from the Epilepsy Study Consortium, Finding a Cure for Epilepsy and Seizures (FACES) and other related foundations, UCB, Pfizer, Eisai, Lundbeck, and Sunovion. Mr. Greenwood and Dr. Donner report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NASHVILLE, TENN. – About 21% of teens newly diagnosed with epilepsy experience suicidal ideation, and the percentage jumps to 31% within 3 years, new research reveals.

“We hope these results inspire epileptologists and neurologists to both recognize and screen for suicide ideation and behaviors in their adolescent patients,” said study investigator Hadley Greenwood, a third-year medical student at New York University.

The new data should also encourage providers “to become more comfortable” providing support to patients, “be that by increasing their familiarity with prescribing different antidepressants or by being well versed in how to connect patients to resources within their community,” said Mr. Greenwood.

The findings were presented here at the annual meeting of the American Epilepsy Society.
 

Little research

Previous studies have reported on the prevalence of suicidality as well as depression and anxiety among adults with epilepsy. “We wanted to look at adolescents because there’s much less in the literature out there about psychiatric comorbidity, and specifically suicidality, in this population,” said Mr. Greenwood.

Researchers used data from the Human Epilepsy Project, a study that collected data from 34 sites in the United States, Canada, Europe, and Australia from 2012 to 2017.

From a cohort of more than 400 participants, researchers identified 67 patients aged 11-17 years who were enrolled within 4 months of starting treatment for focal epilepsy.

Participants completed the Columbia–Suicide Severity Rating Scale (C-SSRS) at enrollment and at follow-ups over 36 months. The C-SSRS measures suicidal ideation and severity, said Mr. Greenwood.

“It’s scaled from passive suicide ideation, such as thoughts of ‘I wish I were dead’ without active intent, all the way up to active suicidal ideation with a plan and intent.”

Researchers were able to distinguish individuals with passive suicide ideation from those with more serious intentions, said Mr. Greenwood. They used medical records to evaluate the prevalence of suicidal ideation and behavior.

The investigators found that more than one in five (20.9%) teens endorsed any lifetime suicide ideation. This, said Mr. Greenwood, is “roughly equivalent” to the prevalence reported earlier in the adult cohort of the Human Epilepsy Project (21.6%).
 

‘Striking’ rate

The fact that one in five adolescents had any lifetime suicide ideation is “definitely a striking number,” said Mr. Greenwood.

Researchers found that 15% of patients experienced active suicide ideation, 7.5% exhibited preparatory or suicidal behaviors, and 3% had made a prior suicide attempt.

All of these percentages increased at 3 years: Thirty-one percent for suicide ideation; 25% for active suicide behavior, 15% for preparatory or suicide behaviors, and 5% for prior suicide attempt.

The fact that nearly one in three adolescents endorsed suicide ideation at 3 years is another “striking” finding, said Mr. Greenwood.

Of the 53 adolescents who had never had suicide ideation at the time of enrollment, 7 endorsed new-onset suicide ideation in the follow-up period. Five of 14 who had had suicide ideation at some point prior to enrollment continued to endorse it.

“The value of the study is identifying the prevalence and identifying the significant number of adolescents with epilepsy who are endorsing either suicide ideation or suicidal behaviors,” said Mr. Greenwood.

The researchers found that among younger teens (aged 11–14 years) rates of suicide ideation were higher than among their older counterparts (aged 15–17 years).

The study does not shed light on the biological connection between epilepsy and suicidality, but Mr. Greenwood noted that prior research has suggested a bidirectional relationship.

“Depression and other psychiatric comorbidities might exist prior to epileptic activity and actually predispose to epileptic activity.”

Mr. Greenwood noted that suicide ideation has “spiked” recently across the general population, and so it’s difficult to compare the prevalence in her study with “today’s prevalence.”

However, other research generally shows that the suicide ideation rate in the general adolescent population is much lower than in teens with epilepsy.

Unique aspects of the current study are that it reports suicide ideation and behaviors at around the time of an epilepsy diagnosis and documents how suicidality progresses or resolves over time, said Mr. Greenwood.
 

Underdiagnosed, undertreated

Commenting on the research, Elizabeth Donner, MD, director of the comprehensive epilepsy program, Hospital for Sick Children, and associate professor, department of pediatrics, University of Toronto, said a “key point” from the study is that the suicidality rate among teens with epilepsy exceeds that of children not living with epilepsy.

“We are significantly underdiagnosing and undertreating the mental health comorbidities in epilepsy,” said Dr. Donner. “Epilepsy is a brain disease and so are mental health disorders, so it shouldn’t come as any surprise that they coexist in individuals with epilepsy.”

The new results contribute to what is already known about the significant mortality rates among persons with epilepsy, said Dr. Donner. She referred to a 2018 study that showed that people with epilepsy were 3.5 times more likely to die by suicide.

Other research has shown that people with epilepsy are 10 times more likely to die by drowning, mostly in the bathtub, said Dr. Donner.

“You would think that we’re educating these people about risks related to their epilepsy, but either the messages don’t get through, or they don’t know how to keep themselves safe,” she said.

“This needs to be seen in a bigger picture, and the bigger picture is we need to recognize comorbid mental health issues; we need to address them once recognized; and then we need to counsel and support people to live safely with their epilepsy.

The study received funding from the Epilepsy Study Consortium, Finding a Cure for Epilepsy and Seizures (FACES) and other related foundations, UCB, Pfizer, Eisai, Lundbeck, and Sunovion. Mr. Greenwood and Dr. Donner report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NASHVILLE, TENN. – About 21% of teens newly diagnosed with epilepsy experience suicidal ideation, and the percentage jumps to 31% within 3 years, new research reveals.

“We hope these results inspire epileptologists and neurologists to both recognize and screen for suicide ideation and behaviors in their adolescent patients,” said study investigator Hadley Greenwood, a third-year medical student at New York University.

The new data should also encourage providers “to become more comfortable” providing support to patients, “be that by increasing their familiarity with prescribing different antidepressants or by being well versed in how to connect patients to resources within their community,” said Mr. Greenwood.

The findings were presented here at the annual meeting of the American Epilepsy Society.
 

Little research

Previous studies have reported on the prevalence of suicidality as well as depression and anxiety among adults with epilepsy. “We wanted to look at adolescents because there’s much less in the literature out there about psychiatric comorbidity, and specifically suicidality, in this population,” said Mr. Greenwood.

Researchers used data from the Human Epilepsy Project, a study that collected data from 34 sites in the United States, Canada, Europe, and Australia from 2012 to 2017.

From a cohort of more than 400 participants, researchers identified 67 patients aged 11-17 years who were enrolled within 4 months of starting treatment for focal epilepsy.

Participants completed the Columbia–Suicide Severity Rating Scale (C-SSRS) at enrollment and at follow-ups over 36 months. The C-SSRS measures suicidal ideation and severity, said Mr. Greenwood.

“It’s scaled from passive suicide ideation, such as thoughts of ‘I wish I were dead’ without active intent, all the way up to active suicidal ideation with a plan and intent.”

Researchers were able to distinguish individuals with passive suicide ideation from those with more serious intentions, said Mr. Greenwood. They used medical records to evaluate the prevalence of suicidal ideation and behavior.

The investigators found that more than one in five (20.9%) teens endorsed any lifetime suicide ideation. This, said Mr. Greenwood, is “roughly equivalent” to the prevalence reported earlier in the adult cohort of the Human Epilepsy Project (21.6%).
 

‘Striking’ rate

The fact that one in five adolescents had any lifetime suicide ideation is “definitely a striking number,” said Mr. Greenwood.

Researchers found that 15% of patients experienced active suicide ideation, 7.5% exhibited preparatory or suicidal behaviors, and 3% had made a prior suicide attempt.

All of these percentages increased at 3 years: Thirty-one percent for suicide ideation; 25% for active suicide behavior, 15% for preparatory or suicide behaviors, and 5% for prior suicide attempt.

The fact that nearly one in three adolescents endorsed suicide ideation at 3 years is another “striking” finding, said Mr. Greenwood.

Of the 53 adolescents who had never had suicide ideation at the time of enrollment, 7 endorsed new-onset suicide ideation in the follow-up period. Five of 14 who had had suicide ideation at some point prior to enrollment continued to endorse it.

“The value of the study is identifying the prevalence and identifying the significant number of adolescents with epilepsy who are endorsing either suicide ideation or suicidal behaviors,” said Mr. Greenwood.

The researchers found that among younger teens (aged 11–14 years) rates of suicide ideation were higher than among their older counterparts (aged 15–17 years).

The study does not shed light on the biological connection between epilepsy and suicidality, but Mr. Greenwood noted that prior research has suggested a bidirectional relationship.

“Depression and other psychiatric comorbidities might exist prior to epileptic activity and actually predispose to epileptic activity.”

Mr. Greenwood noted that suicide ideation has “spiked” recently across the general population, and so it’s difficult to compare the prevalence in her study with “today’s prevalence.”

However, other research generally shows that the suicide ideation rate in the general adolescent population is much lower than in teens with epilepsy.

Unique aspects of the current study are that it reports suicide ideation and behaviors at around the time of an epilepsy diagnosis and documents how suicidality progresses or resolves over time, said Mr. Greenwood.
 

Underdiagnosed, undertreated

Commenting on the research, Elizabeth Donner, MD, director of the comprehensive epilepsy program, Hospital for Sick Children, and associate professor, department of pediatrics, University of Toronto, said a “key point” from the study is that the suicidality rate among teens with epilepsy exceeds that of children not living with epilepsy.

“We are significantly underdiagnosing and undertreating the mental health comorbidities in epilepsy,” said Dr. Donner. “Epilepsy is a brain disease and so are mental health disorders, so it shouldn’t come as any surprise that they coexist in individuals with epilepsy.”

The new results contribute to what is already known about the significant mortality rates among persons with epilepsy, said Dr. Donner. She referred to a 2018 study that showed that people with epilepsy were 3.5 times more likely to die by suicide.

Other research has shown that people with epilepsy are 10 times more likely to die by drowning, mostly in the bathtub, said Dr. Donner.

“You would think that we’re educating these people about risks related to their epilepsy, but either the messages don’t get through, or they don’t know how to keep themselves safe,” she said.

“This needs to be seen in a bigger picture, and the bigger picture is we need to recognize comorbid mental health issues; we need to address them once recognized; and then we need to counsel and support people to live safely with their epilepsy.

The study received funding from the Epilepsy Study Consortium, Finding a Cure for Epilepsy and Seizures (FACES) and other related foundations, UCB, Pfizer, Eisai, Lundbeck, and Sunovion. Mr. Greenwood and Dr. Donner report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The antidepressant vortioxetine (Trintellix) improved cognition, memory, and depressive symptoms in patients with comorbid major depressive disorder (MDD) and dementia.

The results of the 12-week open-label, single-group study are positive, study investigator Michael Cronquist Christensen, MPA, DrPH, a director with the Lundbeck pharmaceutical company, told this news organization before presenting the results in a poster at the 15th Clinical Trials on Alzheimer’s Disease conference.

“The study confirms earlier findings of improvement in both depressive symptoms and cognitive performance with vortioxetine in patients with depression and dementia and adds to this research that these clinical effects also extend to improvement in health-related quality of life and patients’ daily functioning,” Dr. Christensen said.

“It also demonstrates that patients with depression and comorbid dementia can be safely treated with 20 mg vortioxetine – starting dose of 5 mg for the first week and up-titration to 10 mg at day 8,” he added.

However, he reported that Lundbeck doesn’t plan to seek approval from the U.S. Food and Drug Administration for a new indication. Vortioxetine received FDA approval in 2013 to treat MDD, but 3 years later the agency rejected an expansion of its indication to include cognitive dysfunction.

“Vortioxetine is approved for MDD, but the product can be used in patients with MDD who have other diseases, including other mental illnesses,” Dr. Christensen said.

Potential neurotransmission modulator

Vortioxetine is a selective serotonin reuptake inhibitor and serotonin receptor modulator. According to Dr. Christensen, evidence suggests the drug’s receptor targets “have the potential to modulate neurotransmitter systems that are essential for regulation of cognitive function.”

The researchers recruited 83 individuals aged 55-85 with recurrent MDD that had started before the age of 55. All had MDD episodes within the previous 6 months and comorbid dementia for at least 6 months.

Of the participants, 65.9% were female. In addition, 42.7% had Alzheimer’s disease, 26.8% had mixed-type dementia, and the rest had other types of dementia.

The daily oral dose of vortioxetine started at 5 mg for up to week 1 and then was increased to 10 mg. It was then increased to 20 mg or decreased to 5 mg “based on investigator judgment and patient response.” The average daily dose was 12.3 mg.

In regard to the primary outcome, at week 12 (n = 70), scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) fell by a mean of –12.4 (.78, P < .0001), which researchers deemed to be a significant reduction in severe symptoms.

“A significant and clinically meaningful effect was observed from week 1,” the researchers reported.

“As a basis for comparison, we typically see an improvement around 13-14 points during 8 weeks of antidepressant treatment in adults with MDD who do not have dementia,” Dr. Christensen added.

More than a third of patients (35.7%) saw a reduction in MADRS score by more than 50% at week 12, and 17.2% were considered to have reached MDD depression remission, defined as a MADRS score at or under 10.

For secondary outcomes, the total Digit Symbol Substitution test score grew by 0.65 (standardized effect size) by week 12, showing significant improvement (P < .0001). In addition, participants improved on some other cognitive measures, and Dr. Christensen noted that “significant improvement was also observed in the patients’ health-related quality of life and daily functioning.”

A third of patients had drug-related treatment-emergent adverse events.

Vortioxetine is one of the most expensive antidepressants: It has a list price of $444 a month, and no generic version is currently available.

Small trial, open-label design

In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, said the study “reflects a valuable aspect of treatment research because of the close connection between depression and dementia. Depression is a known risk factor for dementia, including Alzheimer’s disease, and those who have dementia may experience depression.”

Alzheimer’s Association

She cautioned, however, that the trial was small and had an open-label design instead of the “gold standard” of a double-blinded trial with a control group.

The study was funded by Lundbeck, where Dr. Christensen is an employee. Another author is a Lundbeck employee, and a third author reported various disclosures. Dr. Sexton reported no disclosures.

A version of this article first appeared on Medscape.com.

The antidepressant vortioxetine (Trintellix) improved cognition, memory, and depressive symptoms in patients with comorbid major depressive disorder (MDD) and dementia.

The results of the 12-week open-label, single-group study are positive, study investigator Michael Cronquist Christensen, MPA, DrPH, a director with the Lundbeck pharmaceutical company, told this news organization before presenting the results in a poster at the 15th Clinical Trials on Alzheimer’s Disease conference.

“The study confirms earlier findings of improvement in both depressive symptoms and cognitive performance with vortioxetine in patients with depression and dementia and adds to this research that these clinical effects also extend to improvement in health-related quality of life and patients’ daily functioning,” Dr. Christensen said.

“It also demonstrates that patients with depression and comorbid dementia can be safely treated with 20 mg vortioxetine – starting dose of 5 mg for the first week and up-titration to 10 mg at day 8,” he added.

However, he reported that Lundbeck doesn’t plan to seek approval from the U.S. Food and Drug Administration for a new indication. Vortioxetine received FDA approval in 2013 to treat MDD, but 3 years later the agency rejected an expansion of its indication to include cognitive dysfunction.

“Vortioxetine is approved for MDD, but the product can be used in patients with MDD who have other diseases, including other mental illnesses,” Dr. Christensen said.

Potential neurotransmission modulator

Vortioxetine is a selective serotonin reuptake inhibitor and serotonin receptor modulator. According to Dr. Christensen, evidence suggests the drug’s receptor targets “have the potential to modulate neurotransmitter systems that are essential for regulation of cognitive function.”

The researchers recruited 83 individuals aged 55-85 with recurrent MDD that had started before the age of 55. All had MDD episodes within the previous 6 months and comorbid dementia for at least 6 months.

Of the participants, 65.9% were female. In addition, 42.7% had Alzheimer’s disease, 26.8% had mixed-type dementia, and the rest had other types of dementia.

The daily oral dose of vortioxetine started at 5 mg for up to week 1 and then was increased to 10 mg. It was then increased to 20 mg or decreased to 5 mg “based on investigator judgment and patient response.” The average daily dose was 12.3 mg.

In regard to the primary outcome, at week 12 (n = 70), scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) fell by a mean of –12.4 (.78, P < .0001), which researchers deemed to be a significant reduction in severe symptoms.

“A significant and clinically meaningful effect was observed from week 1,” the researchers reported.

“As a basis for comparison, we typically see an improvement around 13-14 points during 8 weeks of antidepressant treatment in adults with MDD who do not have dementia,” Dr. Christensen added.

More than a third of patients (35.7%) saw a reduction in MADRS score by more than 50% at week 12, and 17.2% were considered to have reached MDD depression remission, defined as a MADRS score at or under 10.

For secondary outcomes, the total Digit Symbol Substitution test score grew by 0.65 (standardized effect size) by week 12, showing significant improvement (P < .0001). In addition, participants improved on some other cognitive measures, and Dr. Christensen noted that “significant improvement was also observed in the patients’ health-related quality of life and daily functioning.”

A third of patients had drug-related treatment-emergent adverse events.

Vortioxetine is one of the most expensive antidepressants: It has a list price of $444 a month, and no generic version is currently available.

Small trial, open-label design

In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, said the study “reflects a valuable aspect of treatment research because of the close connection between depression and dementia. Depression is a known risk factor for dementia, including Alzheimer’s disease, and those who have dementia may experience depression.”

Alzheimer’s Association

She cautioned, however, that the trial was small and had an open-label design instead of the “gold standard” of a double-blinded trial with a control group.

The study was funded by Lundbeck, where Dr. Christensen is an employee. Another author is a Lundbeck employee, and a third author reported various disclosures. Dr. Sexton reported no disclosures.

A version of this article first appeared on Medscape.com.

The antidepressant vortioxetine (Trintellix) improved cognition, memory, and depressive symptoms in patients with comorbid major depressive disorder (MDD) and dementia.

The results of the 12-week open-label, single-group study are positive, study investigator Michael Cronquist Christensen, MPA, DrPH, a director with the Lundbeck pharmaceutical company, told this news organization before presenting the results in a poster at the 15th Clinical Trials on Alzheimer’s Disease conference.

“The study confirms earlier findings of improvement in both depressive symptoms and cognitive performance with vortioxetine in patients with depression and dementia and adds to this research that these clinical effects also extend to improvement in health-related quality of life and patients’ daily functioning,” Dr. Christensen said.

“It also demonstrates that patients with depression and comorbid dementia can be safely treated with 20 mg vortioxetine – starting dose of 5 mg for the first week and up-titration to 10 mg at day 8,” he added.

However, he reported that Lundbeck doesn’t plan to seek approval from the U.S. Food and Drug Administration for a new indication. Vortioxetine received FDA approval in 2013 to treat MDD, but 3 years later the agency rejected an expansion of its indication to include cognitive dysfunction.

“Vortioxetine is approved for MDD, but the product can be used in patients with MDD who have other diseases, including other mental illnesses,” Dr. Christensen said.

Potential neurotransmission modulator

Vortioxetine is a selective serotonin reuptake inhibitor and serotonin receptor modulator. According to Dr. Christensen, evidence suggests the drug’s receptor targets “have the potential to modulate neurotransmitter systems that are essential for regulation of cognitive function.”

The researchers recruited 83 individuals aged 55-85 with recurrent MDD that had started before the age of 55. All had MDD episodes within the previous 6 months and comorbid dementia for at least 6 months.

Of the participants, 65.9% were female. In addition, 42.7% had Alzheimer’s disease, 26.8% had mixed-type dementia, and the rest had other types of dementia.

The daily oral dose of vortioxetine started at 5 mg for up to week 1 and then was increased to 10 mg. It was then increased to 20 mg or decreased to 5 mg “based on investigator judgment and patient response.” The average daily dose was 12.3 mg.

In regard to the primary outcome, at week 12 (n = 70), scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) fell by a mean of –12.4 (.78, P < .0001), which researchers deemed to be a significant reduction in severe symptoms.

“A significant and clinically meaningful effect was observed from week 1,” the researchers reported.

“As a basis for comparison, we typically see an improvement around 13-14 points during 8 weeks of antidepressant treatment in adults with MDD who do not have dementia,” Dr. Christensen added.

More than a third of patients (35.7%) saw a reduction in MADRS score by more than 50% at week 12, and 17.2% were considered to have reached MDD depression remission, defined as a MADRS score at or under 10.

For secondary outcomes, the total Digit Symbol Substitution test score grew by 0.65 (standardized effect size) by week 12, showing significant improvement (P < .0001). In addition, participants improved on some other cognitive measures, and Dr. Christensen noted that “significant improvement was also observed in the patients’ health-related quality of life and daily functioning.”

A third of patients had drug-related treatment-emergent adverse events.

Vortioxetine is one of the most expensive antidepressants: It has a list price of $444 a month, and no generic version is currently available.

Small trial, open-label design

In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, said the study “reflects a valuable aspect of treatment research because of the close connection between depression and dementia. Depression is a known risk factor for dementia, including Alzheimer’s disease, and those who have dementia may experience depression.”

Alzheimer’s Association

She cautioned, however, that the trial was small and had an open-label design instead of the “gold standard” of a double-blinded trial with a control group.

The study was funded by Lundbeck, where Dr. Christensen is an employee. Another author is a Lundbeck employee, and a third author reported various disclosures. Dr. Sexton reported no disclosures.

A version of this article first appeared on Medscape.com.

Children and young adults who are exposed to a single CT scan of the head or neck before age 22 years are at significantly increased risk of developing a brain tumor, particularly glioma, after at least 5 years, according to results of the large EPI-CT study.

“Translation of our risk estimates to the clinical setting indicates that per 10,000 children who received one head CT examination, about one radiation-induced brain cancer is expected during the 5-15 years following the CT examination,” noted lead author Michael Hauptmann, PhD, from the Institute of Biostatistics and Registry Research, Brandenburg Medical School, Neuruppin, Germany, and coauthors.

“Next to the clinical benefit of most CT scans, there is a small risk of cancer from the radiation exposure,” Dr. Hauptmann told this news organization.

“So, CT examinations should only be used when necessary, and if they are used, the lowest achievable dose should be applied,” he said.

The study was published online in The Lancet Oncology.

“This is a thoughtful and well-conducted study by an outstanding multinational team of scientists that adds further weight to the growing body of evidence that has found exposure to CT scanning increases a child’s risk of developing brain cancer,” commented Rebecca Bindman-Smith, MD, from the University of California, San Francisco, who was not involved in the research.

“The results are real, and important,” she told this news organization, adding that “the authors were conservative in their assumptions, and performed a very large number of sensitivity analyses ... to check that the results were robust to a large range of assumptions – and the results changed relatively little.”

“I do not think there is enough awareness [about this risk],” Dr. Hauptmann said. “There is evidence that a nonnegligible number of CTs is unjustified according to guidelines, and there is evidence that doses vary substantially for the same CT between institutions in the same or different countries.”

Indeed, particularly in the United States, “we perform many CT scans in children and even more so in adults that are simply unnecessary,” agreed Dr. Bindman-Smith, who is professor of epidemiology and biostatistics at the University of California, San Francisco. “It is important for patients and providers to understand that nothing we do in medicine is risk free, including CT scanning. If a CT is necessary, the benefit almost certainly outweighs the risk. But if [not], then it should not be obtained. Both patients and providers must make thoroughly considered decisions before asking for or agreeing to a CT.”

She also pointed out that while this study evaluated the risk only for brain cancer, children who undergo head CTs are also at increased risk for leukemia.
 

Dose/response relationship

The study included 658,752 individuals from nine European countries and 276 hospitals. Each patient had received at least one CT scan between 1977 and 2014 before they turned 22 years of age. Eligibility requirements included their being alive at least 5 years after the first scan and that they had not previously been diagnosed with cancer or benign brain tumor.

The radiation dose absorbed to the brain and 33 other organs and tissues was estimated for each participant using a dose reconstruction model that included historical information on CT machine settings, questionnaire data, and Digital Imaging and Communication in Medicine header metadata. “Mean brain dose per head or neck CT examination increased from 1984 until about 1991, following the introduction of multislice CT scanners at which point thereafter the mean dose decreased and then stabilized around 2010,” note the authors.

During a median follow-up of 5.6 years (starting 5 years after the first scan), 165 brain cancers occurred, including 121 (73%) gliomas, as well as a variety of other morphologic changes.

The mean cumulative brain dose, which lagged by 5 years, was 47.4 mGy overall and 76.0 mGy among people with brain cancer.

“We observed a significant positive association between the cumulative number of head or neck CT examinations and the risk of all brain cancers combined (P < .0001), and of gliomas separately (P = .0002),” the team reports, adding that, for a brain dose of 38 mGy, which was the average dose per head or neck CT in 2012-2014, the relative risk of developing brain cancer was 1.5, compared with not undergoing a CT scan, and the excess absolute risk per 100,000 person-years was 1.1.

These findings “can be used to give the patients and their parents important information on the risks of CT examination to balance against the known benefits,” noted Nobuyuki Hamada, PhD, from the Central Research Institute of Electric Power Industry, Tokyo, and Lydia B. Zablotska, MD, PhD, from the University of California, San Francisco, writing in a linked commentary.

“In recent years, rates of CT use have been steady or declined, and various efforts (for instance, in terms of diagnostic reference levels) have been made to justify and optimize CT examinations. Such continued efforts, along with extended epidemiological investigations, would be needed to minimize the risk of brain cancer after pediatric CT examination,” they add.
 

Keeping dose to a minimum

The study’s finding of a dose-response relationship underscores the importance of keeping doses to a minimum, Dr. Bindman-Smith commented. “I do not believe we are doing this nearly enough,” she added.

“In the UCSF International CT Dose Registry, where we have collected CT scans from 165 hospitals on many millions of patients, we found that the average brain dose for a head CT in a 1-year-old is 42 mGy but that this dose varies tremendously, where some children receive a dose of 100 mGy.

“So, a second message is that not only should CT scans be justified and used judiciously, but also they should be optimized, meaning using the lowest dose possible. I personally think there should be regulatory oversight to ensure that patients receive the absolutely lowest doses possible,” she added. “My team at UCSF has written quality measures endorsed by the National Quality Forum as a start for setting explicit standards for how CT should be performed in order to ensure the cancer risks are as low as possible.”

The study was funded through the Belgian Cancer Registry; La Ligue contre le Cancer, L’Institut National du Cancer, France; the Ministry of Health, Labour and Welfare of Japan; the German Federal Ministry of Education and Research; Worldwide Cancer Research; the Dutch Cancer Society; the Research Council of Norway; Consejo de Seguridad Nuclear, Generalitat deCatalunya, Spain; the U.S. National Cancer Institute; the U.K. National Institute for Health Research; and Public Health England. Dr. Hauptmann has disclosed no relevant financial relationships. Other investigators’ relevant financial relationships are listed in the original article. Dr. Hamada and Dr. Zablotska disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Children and young adults who are exposed to a single CT scan of the head or neck before age 22 years are at significantly increased risk of developing a brain tumor, particularly glioma, after at least 5 years, according to results of the large EPI-CT study.

“Translation of our risk estimates to the clinical setting indicates that per 10,000 children who received one head CT examination, about one radiation-induced brain cancer is expected during the 5-15 years following the CT examination,” noted lead author Michael Hauptmann, PhD, from the Institute of Biostatistics and Registry Research, Brandenburg Medical School, Neuruppin, Germany, and coauthors.

“Next to the clinical benefit of most CT scans, there is a small risk of cancer from the radiation exposure,” Dr. Hauptmann told this news organization.

“So, CT examinations should only be used when necessary, and if they are used, the lowest achievable dose should be applied,” he said.

The study was published online in The Lancet Oncology.

“This is a thoughtful and well-conducted study by an outstanding multinational team of scientists that adds further weight to the growing body of evidence that has found exposure to CT scanning increases a child’s risk of developing brain cancer,” commented Rebecca Bindman-Smith, MD, from the University of California, San Francisco, who was not involved in the research.

“The results are real, and important,” she told this news organization, adding that “the authors were conservative in their assumptions, and performed a very large number of sensitivity analyses ... to check that the results were robust to a large range of assumptions – and the results changed relatively little.”

“I do not think there is enough awareness [about this risk],” Dr. Hauptmann said. “There is evidence that a nonnegligible number of CTs is unjustified according to guidelines, and there is evidence that doses vary substantially for the same CT between institutions in the same or different countries.”

Indeed, particularly in the United States, “we perform many CT scans in children and even more so in adults that are simply unnecessary,” agreed Dr. Bindman-Smith, who is professor of epidemiology and biostatistics at the University of California, San Francisco. “It is important for patients and providers to understand that nothing we do in medicine is risk free, including CT scanning. If a CT is necessary, the benefit almost certainly outweighs the risk. But if [not], then it should not be obtained. Both patients and providers must make thoroughly considered decisions before asking for or agreeing to a CT.”

She also pointed out that while this study evaluated the risk only for brain cancer, children who undergo head CTs are also at increased risk for leukemia.
 

Dose/response relationship

The study included 658,752 individuals from nine European countries and 276 hospitals. Each patient had received at least one CT scan between 1977 and 2014 before they turned 22 years of age. Eligibility requirements included their being alive at least 5 years after the first scan and that they had not previously been diagnosed with cancer or benign brain tumor.

The radiation dose absorbed to the brain and 33 other organs and tissues was estimated for each participant using a dose reconstruction model that included historical information on CT machine settings, questionnaire data, and Digital Imaging and Communication in Medicine header metadata. “Mean brain dose per head or neck CT examination increased from 1984 until about 1991, following the introduction of multislice CT scanners at which point thereafter the mean dose decreased and then stabilized around 2010,” note the authors.

During a median follow-up of 5.6 years (starting 5 years after the first scan), 165 brain cancers occurred, including 121 (73%) gliomas, as well as a variety of other morphologic changes.

The mean cumulative brain dose, which lagged by 5 years, was 47.4 mGy overall and 76.0 mGy among people with brain cancer.

“We observed a significant positive association between the cumulative number of head or neck CT examinations and the risk of all brain cancers combined (P < .0001), and of gliomas separately (P = .0002),” the team reports, adding that, for a brain dose of 38 mGy, which was the average dose per head or neck CT in 2012-2014, the relative risk of developing brain cancer was 1.5, compared with not undergoing a CT scan, and the excess absolute risk per 100,000 person-years was 1.1.

These findings “can be used to give the patients and their parents important information on the risks of CT examination to balance against the known benefits,” noted Nobuyuki Hamada, PhD, from the Central Research Institute of Electric Power Industry, Tokyo, and Lydia B. Zablotska, MD, PhD, from the University of California, San Francisco, writing in a linked commentary.

“In recent years, rates of CT use have been steady or declined, and various efforts (for instance, in terms of diagnostic reference levels) have been made to justify and optimize CT examinations. Such continued efforts, along with extended epidemiological investigations, would be needed to minimize the risk of brain cancer after pediatric CT examination,” they add.
 

Keeping dose to a minimum

The study’s finding of a dose-response relationship underscores the importance of keeping doses to a minimum, Dr. Bindman-Smith commented. “I do not believe we are doing this nearly enough,” she added.

“In the UCSF International CT Dose Registry, where we have collected CT scans from 165 hospitals on many millions of patients, we found that the average brain dose for a head CT in a 1-year-old is 42 mGy but that this dose varies tremendously, where some children receive a dose of 100 mGy.

“So, a second message is that not only should CT scans be justified and used judiciously, but also they should be optimized, meaning using the lowest dose possible. I personally think there should be regulatory oversight to ensure that patients receive the absolutely lowest doses possible,” she added. “My team at UCSF has written quality measures endorsed by the National Quality Forum as a start for setting explicit standards for how CT should be performed in order to ensure the cancer risks are as low as possible.”

The study was funded through the Belgian Cancer Registry; La Ligue contre le Cancer, L’Institut National du Cancer, France; the Ministry of Health, Labour and Welfare of Japan; the German Federal Ministry of Education and Research; Worldwide Cancer Research; the Dutch Cancer Society; the Research Council of Norway; Consejo de Seguridad Nuclear, Generalitat deCatalunya, Spain; the U.S. National Cancer Institute; the U.K. National Institute for Health Research; and Public Health England. Dr. Hauptmann has disclosed no relevant financial relationships. Other investigators’ relevant financial relationships are listed in the original article. Dr. Hamada and Dr. Zablotska disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Children and young adults who are exposed to a single CT scan of the head or neck before age 22 years are at significantly increased risk of developing a brain tumor, particularly glioma, after at least 5 years, according to results of the large EPI-CT study.

“Translation of our risk estimates to the clinical setting indicates that per 10,000 children who received one head CT examination, about one radiation-induced brain cancer is expected during the 5-15 years following the CT examination,” noted lead author Michael Hauptmann, PhD, from the Institute of Biostatistics and Registry Research, Brandenburg Medical School, Neuruppin, Germany, and coauthors.

“Next to the clinical benefit of most CT scans, there is a small risk of cancer from the radiation exposure,” Dr. Hauptmann told this news organization.

“So, CT examinations should only be used when necessary, and if they are used, the lowest achievable dose should be applied,” he said.

The study was published online in The Lancet Oncology.

“This is a thoughtful and well-conducted study by an outstanding multinational team of scientists that adds further weight to the growing body of evidence that has found exposure to CT scanning increases a child’s risk of developing brain cancer,” commented Rebecca Bindman-Smith, MD, from the University of California, San Francisco, who was not involved in the research.

“The results are real, and important,” she told this news organization, adding that “the authors were conservative in their assumptions, and performed a very large number of sensitivity analyses ... to check that the results were robust to a large range of assumptions – and the results changed relatively little.”

“I do not think there is enough awareness [about this risk],” Dr. Hauptmann said. “There is evidence that a nonnegligible number of CTs is unjustified according to guidelines, and there is evidence that doses vary substantially for the same CT between institutions in the same or different countries.”

Indeed, particularly in the United States, “we perform many CT scans in children and even more so in adults that are simply unnecessary,” agreed Dr. Bindman-Smith, who is professor of epidemiology and biostatistics at the University of California, San Francisco. “It is important for patients and providers to understand that nothing we do in medicine is risk free, including CT scanning. If a CT is necessary, the benefit almost certainly outweighs the risk. But if [not], then it should not be obtained. Both patients and providers must make thoroughly considered decisions before asking for or agreeing to a CT.”

She also pointed out that while this study evaluated the risk only for brain cancer, children who undergo head CTs are also at increased risk for leukemia.
 

Dose/response relationship

The study included 658,752 individuals from nine European countries and 276 hospitals. Each patient had received at least one CT scan between 1977 and 2014 before they turned 22 years of age. Eligibility requirements included their being alive at least 5 years after the first scan and that they had not previously been diagnosed with cancer or benign brain tumor.

The radiation dose absorbed to the brain and 33 other organs and tissues was estimated for each participant using a dose reconstruction model that included historical information on CT machine settings, questionnaire data, and Digital Imaging and Communication in Medicine header metadata. “Mean brain dose per head or neck CT examination increased from 1984 until about 1991, following the introduction of multislice CT scanners at which point thereafter the mean dose decreased and then stabilized around 2010,” note the authors.

During a median follow-up of 5.6 years (starting 5 years after the first scan), 165 brain cancers occurred, including 121 (73%) gliomas, as well as a variety of other morphologic changes.

The mean cumulative brain dose, which lagged by 5 years, was 47.4 mGy overall and 76.0 mGy among people with brain cancer.

“We observed a significant positive association between the cumulative number of head or neck CT examinations and the risk of all brain cancers combined (P < .0001), and of gliomas separately (P = .0002),” the team reports, adding that, for a brain dose of 38 mGy, which was the average dose per head or neck CT in 2012-2014, the relative risk of developing brain cancer was 1.5, compared with not undergoing a CT scan, and the excess absolute risk per 100,000 person-years was 1.1.

These findings “can be used to give the patients and their parents important information on the risks of CT examination to balance against the known benefits,” noted Nobuyuki Hamada, PhD, from the Central Research Institute of Electric Power Industry, Tokyo, and Lydia B. Zablotska, MD, PhD, from the University of California, San Francisco, writing in a linked commentary.

“In recent years, rates of CT use have been steady or declined, and various efforts (for instance, in terms of diagnostic reference levels) have been made to justify and optimize CT examinations. Such continued efforts, along with extended epidemiological investigations, would be needed to minimize the risk of brain cancer after pediatric CT examination,” they add.
 

Keeping dose to a minimum

The study’s finding of a dose-response relationship underscores the importance of keeping doses to a minimum, Dr. Bindman-Smith commented. “I do not believe we are doing this nearly enough,” she added.

“In the UCSF International CT Dose Registry, where we have collected CT scans from 165 hospitals on many millions of patients, we found that the average brain dose for a head CT in a 1-year-old is 42 mGy but that this dose varies tremendously, where some children receive a dose of 100 mGy.

“So, a second message is that not only should CT scans be justified and used judiciously, but also they should be optimized, meaning using the lowest dose possible. I personally think there should be regulatory oversight to ensure that patients receive the absolutely lowest doses possible,” she added. “My team at UCSF has written quality measures endorsed by the National Quality Forum as a start for setting explicit standards for how CT should be performed in order to ensure the cancer risks are as low as possible.”

The study was funded through the Belgian Cancer Registry; La Ligue contre le Cancer, L’Institut National du Cancer, France; the Ministry of Health, Labour and Welfare of Japan; the German Federal Ministry of Education and Research; Worldwide Cancer Research; the Dutch Cancer Society; the Research Council of Norway; Consejo de Seguridad Nuclear, Generalitat deCatalunya, Spain; the U.S. National Cancer Institute; the U.K. National Institute for Health Research; and Public Health England. Dr. Hauptmann has disclosed no relevant financial relationships. Other investigators’ relevant financial relationships are listed in the original article. Dr. Hamada and Dr. Zablotska disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study has provided further reassurance on questions about the risk of intracerebral hemorrhage (ICH) with statins.

The Danish case-control study, which compared statin use in 2,164 case patients with ICH and in 86,255 matched control persons, found that current statin use was associated with a lower risk of having a first ICH and that the risk was further reduced with longer duration of statin use.

The study also showed that statin use was linked to a lower risk of ICH in the more superficial lobar areas of the brain and in the deeper, nonlobar locations. There was no difference in the magnitude of risk reduction between the two locations.

“Although this study is observational, I feel these data are strong, and the results are reassuring. It certainly does not suggest any increased risk of ICH with statins,” senior author David Gaist, PhD, Odense University Hospital, Denmark, said in an interview.

“On the contrary, it indicates a lower risk, which seems to be independent of the location of the bleed.”

The study was published online in Neurology.

The authors note that statins effectively reduce the occurrence of cardiovascular events and ischemic stroke in high-risk populations, but early randomized trials raised concerns of an increased risk of ICH among statin users who have a history of stroke.

Subsequent observational studies, including four meta-analyses, included patients with and those without prior stroke. The results were inconsistent, although most found no increase in bleeding. More recent studies have found a lower risk of ICH among statin users; the risk was inversely associated with the duration and intensity of statin treatment.

However, the researchers point out that few studies have assessed the association between statin use and the location of ICH. Hemorrhages that occur in the lobar region of the brain and those that occur in the nonlobar areas can have different pathophysiologies. Arteriolosclerosis, which is strongly associated with hypertension, is a common histologic finding in patients with ICH, regardless of hemorrhage location, while cerebral amyloid angiopathy (CAA) is associated with lobar but not nonlobar ICH.

The current study was conducted to look more closely at the relationship between statin use and hematoma location as a reflection of differences in the underlying pathophysiologies of lobar versus nonlobar ICH.

The researchers used Danish registries to identify all first-ever cases of spontaneous ICH that occurred between 2009 and 2018 in persons older than 55 years in the Southern Denmark region. Patients with traumatic ICH or ICH related to vascular malformations and tumors were excluded.

These cases were verified through medical records. ICH diagnoses were classified as having a lobar or nonlobar location, and patients were matched for age, sex, and calendar year to general population control persons. The nationwide prescription registry was also analyzed to ascertain use of statins and other medications.

The study included 989 patients with lobar ICH who were matched to 39,500 control persons and 1,175 patients with nonlobar ICH who were matched to 46,755 control persons.

Results showed that current statin use was associated with a 16%-17% relative reduction in ICH risk. There was no difference with respect to ICH location.

For lobar ICH, statin use showed an adjusted odds ratio of 0.83 (95% confidence interval, 0.70-0.98); for nonlobar ICH, the adjusted odds ratio was 0.84 (95% CI, 0.72-0.98).

Longer duration of statin use was associated with a greater reduction in risk of ICH; use for more than 5 years was associated with a relative reduction of ICH of 33%-38%, again with no difference with regard to ICH location.

For lobar ICH, statin use for more than 5 years showed an adjusted odds ratio of 0.67 (95% CI, 0.51-0.87); and for nonlobar ICH, the adjusted odds ratio was 0.62 (95% CI, 0.48-0.80).

“We suspected that statins may have more of an effect in reducing nonlobar ICH, as this type is considered to be more associated with arteriosclerosis, compared with lobar ICH,” Dr. Gaist explained. “But we didn’t find that. We found that taking statins was associated with a similar reduction in risk of both lobar and nonlobar ICH.”

Although amyloid angiopathy can contribute to lobar ICH, arteriosclerosis is still involved in the majority of cases, he noted. He cited a recent population-based U.K. study that showed that while histologically verified CAA was present in 58% of patients with a lobar ICH, most also had evidence of arteriosclerosis, with only 13% having isolated CAA pathology.

“If statins exert their effect on reducing ICH by reducing arteriosclerosis, which is likely, then this observation of arteriosclerosis pathology being prevalent in both lobar and nonlobar ICH locations would explain our results,” Dr. Gaist commented.

“Strengths of our study include the large numbers involved and the fact that the patients are unselected. We tried to find everyone who had had a first ICH in a well-defined region of Denmark, so issues of selection are less of a concern than in some other studies,” he noted.

He also pointed out that all the ICH diagnoses were verified from medical records and that in a substudy, brain scans were evaluated, with investigators masked to clinical data to evaluate the location and characteristics of the hematoma. In addition, data on statin use were collected prospectively from a nationwide prescription registry.
 

Interaction with antihypertensives, anticoagulants?

Other results from the study suggest a possible interaction between statin use and antihypertensive and anticoagulant drugs.

Data showed that the lower ICH risk was restricted to patients who received statins and antihypertensive drugs concurrently. Conversely, only patients who were not concurrently taking anticoagulants had a lower risk of ICH in association with statin use.

Dr. Gaist suggested that the lack of a reduction in ICH with statins among patients taking anticoagulants could be because the increased risk of ICH with anticoagulants was stronger than the reduced risk with statins.

Regarding the fact that the reduced risk of ICH with statins was only observed among individuals who were also taking antihypertensive medication, Dr. Gaist noted that because hypertension is such an important risk factor for ICH, “it may be that to get the true benefit of statins, patients have to have their hypertension controlled.”

However, an alternative explanation could that the finding is a result of “healthy adherer” bias, in which people who take antihypertensive medication and follow a healthy lifestyle as advised would be more likely to take statins.

“The observational nature of our study does not allow us to determine the extent to which associations are causal,” the authors say.

Dr. Gaist also noted that an important caveat in this study is that they focused on individuals who had had a first ICH.

“This data does not inform us about those who have already had an ICH and are taking statins. But we are planning to look at this in our next study,” he said.

The study was funded by the Novo Nordisk Foundation. Dr. Gaist has received speaker honorarium from Bristol-Myers Squibb and Pfizer unrelated to this work.

A version of this article first appeared on Medscape.com.

A new study has provided further reassurance on questions about the risk of intracerebral hemorrhage (ICH) with statins.

The Danish case-control study, which compared statin use in 2,164 case patients with ICH and in 86,255 matched control persons, found that current statin use was associated with a lower risk of having a first ICH and that the risk was further reduced with longer duration of statin use.

The study also showed that statin use was linked to a lower risk of ICH in the more superficial lobar areas of the brain and in the deeper, nonlobar locations. There was no difference in the magnitude of risk reduction between the two locations.

“Although this study is observational, I feel these data are strong, and the results are reassuring. It certainly does not suggest any increased risk of ICH with statins,” senior author David Gaist, PhD, Odense University Hospital, Denmark, said in an interview.

“On the contrary, it indicates a lower risk, which seems to be independent of the location of the bleed.”

The study was published online in Neurology.

The authors note that statins effectively reduce the occurrence of cardiovascular events and ischemic stroke in high-risk populations, but early randomized trials raised concerns of an increased risk of ICH among statin users who have a history of stroke.

Subsequent observational studies, including four meta-analyses, included patients with and those without prior stroke. The results were inconsistent, although most found no increase in bleeding. More recent studies have found a lower risk of ICH among statin users; the risk was inversely associated with the duration and intensity of statin treatment.

However, the researchers point out that few studies have assessed the association between statin use and the location of ICH. Hemorrhages that occur in the lobar region of the brain and those that occur in the nonlobar areas can have different pathophysiologies. Arteriolosclerosis, which is strongly associated with hypertension, is a common histologic finding in patients with ICH, regardless of hemorrhage location, while cerebral amyloid angiopathy (CAA) is associated with lobar but not nonlobar ICH.

The current study was conducted to look more closely at the relationship between statin use and hematoma location as a reflection of differences in the underlying pathophysiologies of lobar versus nonlobar ICH.

The researchers used Danish registries to identify all first-ever cases of spontaneous ICH that occurred between 2009 and 2018 in persons older than 55 years in the Southern Denmark region. Patients with traumatic ICH or ICH related to vascular malformations and tumors were excluded.

These cases were verified through medical records. ICH diagnoses were classified as having a lobar or nonlobar location, and patients were matched for age, sex, and calendar year to general population control persons. The nationwide prescription registry was also analyzed to ascertain use of statins and other medications.

The study included 989 patients with lobar ICH who were matched to 39,500 control persons and 1,175 patients with nonlobar ICH who were matched to 46,755 control persons.

Results showed that current statin use was associated with a 16%-17% relative reduction in ICH risk. There was no difference with respect to ICH location.

For lobar ICH, statin use showed an adjusted odds ratio of 0.83 (95% confidence interval, 0.70-0.98); for nonlobar ICH, the adjusted odds ratio was 0.84 (95% CI, 0.72-0.98).

Longer duration of statin use was associated with a greater reduction in risk of ICH; use for more than 5 years was associated with a relative reduction of ICH of 33%-38%, again with no difference with regard to ICH location.

For lobar ICH, statin use for more than 5 years showed an adjusted odds ratio of 0.67 (95% CI, 0.51-0.87); and for nonlobar ICH, the adjusted odds ratio was 0.62 (95% CI, 0.48-0.80).

“We suspected that statins may have more of an effect in reducing nonlobar ICH, as this type is considered to be more associated with arteriosclerosis, compared with lobar ICH,” Dr. Gaist explained. “But we didn’t find that. We found that taking statins was associated with a similar reduction in risk of both lobar and nonlobar ICH.”

Although amyloid angiopathy can contribute to lobar ICH, arteriosclerosis is still involved in the majority of cases, he noted. He cited a recent population-based U.K. study that showed that while histologically verified CAA was present in 58% of patients with a lobar ICH, most also had evidence of arteriosclerosis, with only 13% having isolated CAA pathology.

“If statins exert their effect on reducing ICH by reducing arteriosclerosis, which is likely, then this observation of arteriosclerosis pathology being prevalent in both lobar and nonlobar ICH locations would explain our results,” Dr. Gaist commented.

“Strengths of our study include the large numbers involved and the fact that the patients are unselected. We tried to find everyone who had had a first ICH in a well-defined region of Denmark, so issues of selection are less of a concern than in some other studies,” he noted.

He also pointed out that all the ICH diagnoses were verified from medical records and that in a substudy, brain scans were evaluated, with investigators masked to clinical data to evaluate the location and characteristics of the hematoma. In addition, data on statin use were collected prospectively from a nationwide prescription registry.
 

Interaction with antihypertensives, anticoagulants?

Other results from the study suggest a possible interaction between statin use and antihypertensive and anticoagulant drugs.

Data showed that the lower ICH risk was restricted to patients who received statins and antihypertensive drugs concurrently. Conversely, only patients who were not concurrently taking anticoagulants had a lower risk of ICH in association with statin use.

Dr. Gaist suggested that the lack of a reduction in ICH with statins among patients taking anticoagulants could be because the increased risk of ICH with anticoagulants was stronger than the reduced risk with statins.

Regarding the fact that the reduced risk of ICH with statins was only observed among individuals who were also taking antihypertensive medication, Dr. Gaist noted that because hypertension is such an important risk factor for ICH, “it may be that to get the true benefit of statins, patients have to have their hypertension controlled.”

However, an alternative explanation could that the finding is a result of “healthy adherer” bias, in which people who take antihypertensive medication and follow a healthy lifestyle as advised would be more likely to take statins.

“The observational nature of our study does not allow us to determine the extent to which associations are causal,” the authors say.

Dr. Gaist also noted that an important caveat in this study is that they focused on individuals who had had a first ICH.

“This data does not inform us about those who have already had an ICH and are taking statins. But we are planning to look at this in our next study,” he said.

The study was funded by the Novo Nordisk Foundation. Dr. Gaist has received speaker honorarium from Bristol-Myers Squibb and Pfizer unrelated to this work.

A version of this article first appeared on Medscape.com.

A new study has provided further reassurance on questions about the risk of intracerebral hemorrhage (ICH) with statins.

The Danish case-control study, which compared statin use in 2,164 case patients with ICH and in 86,255 matched control persons, found that current statin use was associated with a lower risk of having a first ICH and that the risk was further reduced with longer duration of statin use.

The study also showed that statin use was linked to a lower risk of ICH in the more superficial lobar areas of the brain and in the deeper, nonlobar locations. There was no difference in the magnitude of risk reduction between the two locations.

“Although this study is observational, I feel these data are strong, and the results are reassuring. It certainly does not suggest any increased risk of ICH with statins,” senior author David Gaist, PhD, Odense University Hospital, Denmark, said in an interview.

“On the contrary, it indicates a lower risk, which seems to be independent of the location of the bleed.”

The study was published online in Neurology.

The authors note that statins effectively reduce the occurrence of cardiovascular events and ischemic stroke in high-risk populations, but early randomized trials raised concerns of an increased risk of ICH among statin users who have a history of stroke.

Subsequent observational studies, including four meta-analyses, included patients with and those without prior stroke. The results were inconsistent, although most found no increase in bleeding. More recent studies have found a lower risk of ICH among statin users; the risk was inversely associated with the duration and intensity of statin treatment.

However, the researchers point out that few studies have assessed the association between statin use and the location of ICH. Hemorrhages that occur in the lobar region of the brain and those that occur in the nonlobar areas can have different pathophysiologies. Arteriolosclerosis, which is strongly associated with hypertension, is a common histologic finding in patients with ICH, regardless of hemorrhage location, while cerebral amyloid angiopathy (CAA) is associated with lobar but not nonlobar ICH.

The current study was conducted to look more closely at the relationship between statin use and hematoma location as a reflection of differences in the underlying pathophysiologies of lobar versus nonlobar ICH.

The researchers used Danish registries to identify all first-ever cases of spontaneous ICH that occurred between 2009 and 2018 in persons older than 55 years in the Southern Denmark region. Patients with traumatic ICH or ICH related to vascular malformations and tumors were excluded.

These cases were verified through medical records. ICH diagnoses were classified as having a lobar or nonlobar location, and patients were matched for age, sex, and calendar year to general population control persons. The nationwide prescription registry was also analyzed to ascertain use of statins and other medications.

The study included 989 patients with lobar ICH who were matched to 39,500 control persons and 1,175 patients with nonlobar ICH who were matched to 46,755 control persons.

Results showed that current statin use was associated with a 16%-17% relative reduction in ICH risk. There was no difference with respect to ICH location.

For lobar ICH, statin use showed an adjusted odds ratio of 0.83 (95% confidence interval, 0.70-0.98); for nonlobar ICH, the adjusted odds ratio was 0.84 (95% CI, 0.72-0.98).

Longer duration of statin use was associated with a greater reduction in risk of ICH; use for more than 5 years was associated with a relative reduction of ICH of 33%-38%, again with no difference with regard to ICH location.

For lobar ICH, statin use for more than 5 years showed an adjusted odds ratio of 0.67 (95% CI, 0.51-0.87); and for nonlobar ICH, the adjusted odds ratio was 0.62 (95% CI, 0.48-0.80).

“We suspected that statins may have more of an effect in reducing nonlobar ICH, as this type is considered to be more associated with arteriosclerosis, compared with lobar ICH,” Dr. Gaist explained. “But we didn’t find that. We found that taking statins was associated with a similar reduction in risk of both lobar and nonlobar ICH.”

Although amyloid angiopathy can contribute to lobar ICH, arteriosclerosis is still involved in the majority of cases, he noted. He cited a recent population-based U.K. study that showed that while histologically verified CAA was present in 58% of patients with a lobar ICH, most also had evidence of arteriosclerosis, with only 13% having isolated CAA pathology.

“If statins exert their effect on reducing ICH by reducing arteriosclerosis, which is likely, then this observation of arteriosclerosis pathology being prevalent in both lobar and nonlobar ICH locations would explain our results,” Dr. Gaist commented.

“Strengths of our study include the large numbers involved and the fact that the patients are unselected. We tried to find everyone who had had a first ICH in a well-defined region of Denmark, so issues of selection are less of a concern than in some other studies,” he noted.

He also pointed out that all the ICH diagnoses were verified from medical records and that in a substudy, brain scans were evaluated, with investigators masked to clinical data to evaluate the location and characteristics of the hematoma. In addition, data on statin use were collected prospectively from a nationwide prescription registry.
 

Interaction with antihypertensives, anticoagulants?

Other results from the study suggest a possible interaction between statin use and antihypertensive and anticoagulant drugs.

Data showed that the lower ICH risk was restricted to patients who received statins and antihypertensive drugs concurrently. Conversely, only patients who were not concurrently taking anticoagulants had a lower risk of ICH in association with statin use.

Dr. Gaist suggested that the lack of a reduction in ICH with statins among patients taking anticoagulants could be because the increased risk of ICH with anticoagulants was stronger than the reduced risk with statins.

Regarding the fact that the reduced risk of ICH with statins was only observed among individuals who were also taking antihypertensive medication, Dr. Gaist noted that because hypertension is such an important risk factor for ICH, “it may be that to get the true benefit of statins, patients have to have their hypertension controlled.”

However, an alternative explanation could that the finding is a result of “healthy adherer” bias, in which people who take antihypertensive medication and follow a healthy lifestyle as advised would be more likely to take statins.

“The observational nature of our study does not allow us to determine the extent to which associations are causal,” the authors say.

Dr. Gaist also noted that an important caveat in this study is that they focused on individuals who had had a first ICH.

“This data does not inform us about those who have already had an ICH and are taking statins. But we are planning to look at this in our next study,” he said.

The study was funded by the Novo Nordisk Foundation. Dr. Gaist has received speaker honorarium from Bristol-Myers Squibb and Pfizer unrelated to this work.

A version of this article first appeared on Medscape.com.

Most of us have two voice changes in our lifetime: First during puberty, as the vocal cords thicken and the voice box migrates down the throat. Then a second time as aging causes structural changes that may weaken the voice.

But for some of us, there’s another voice shift, when a disease begins or when our mental health declines.

This is why more doctors are looking into voice as a biomarker – something that tells you that a disease is present.

Vital signs like blood pressure or heart rate “can give a general idea of how sick we are. But they’re not specific to certain diseases,” says Yael Bensoussan, MD, director of the University of South Florida, Tampa’s Health Voice Center and the coprincipal investigator for the National Institutes of Health’s Voice as a Biomarker of Health project.

“We’re learning that there are patterns” in voice changes that can indicate a range of conditions, including diseases of the nervous system and mental illnesses, she says.

Speaking is complicated, involving everything from the lungs and voice box to the mouth and brain. “A breakdown in any of those parts can affect the voice,” says Maria Powell, PhD, an assistant professor of otolaryngology (the study of diseases of the ear and throat) at Vanderbilt University, Nashville, Tenn., who is working on the NIH project.

You or those around you may not notice the changes. But researchers say voice analysis as a standard part of patient care – akin to blood pressure checks or cholesterol tests – could help identify those who need medical attention earlier.

Often, all it takes is a smartphone – “something that’s cheap, off-the-shelf, and that everyone can use,” says Ariana Anderson, PhD, director of the University of California, Los Angeles, Laboratory of Computational Neuropsychology.

“You can provide voice data in your pajamas, on your couch,” says Frank Rudzicz, PhD, a computer scientist for the NIH project. “It doesn’t require very complicated or expensive equipment, and it doesn’t require a lot of expertise to obtain.” Plus, multiple samples can be collected over time, giving a more accurate picture of health than a single snapshot from, say, a cognitive test.

Over the next 4 years, the Voice as a Biomarker team will receive nearly $18 million to gather a massive amount of voice data. The goal is 20,000-30,000 samples, along with health data about each person being studied. The result will be a sprawling database scientists can use to develop algorithms linking health conditions to the way we speak.

For the first 2 years, new data will be collected exclusively via universities and high-volume clinics to control quality and accuracy. Eventually, people will be invited to submit their own voice recordings, creating a crowdsourced dataset. “Google, Alexa, Amazon – they have access to tons of voice data,” says Dr. Bensoussan. “But it’s not usable in a clinical way, because they don’t have the health information.”

Dr. Bensoussan and her colleagues hope to fill that void with advance voice screening apps, which could prove especially valuable in remote communities that lack access to specialists or as a tool for telemedicine. Down the line, wearable devices with voice analysis could alert people with chronic conditions when they need to see a doctor.

“The watch says, ‘I’ve analyzed your breathing and coughing, and today, you’re really not doing well. You should go to the hospital,’ ” says Dr. Bensoussan, envisioning a wearable for patients with COPD. “It could tell people early that things are declining.”

Artificial intelligence may be better than a brain at pinpointing the right disease. For example, slurred speech could indicate Parkinson’s, a stroke, or ALS, among other things.

“We can hold approximately seven pieces of information in our head at one time,” says Dr. Rudzicz. “It’s really hard for us to get a holistic picture using dozens or hundreds of variables at once.” But a computer can consider a whole range of vocal markers at the same time, piecing them together for a more accurate assessment.

“The goal is not to outperform a ... clinician,” says Dr. Bensoussan. Yet the potential is unmistakably there: In a recent study of patients with cancer of the larynx, an automated voice analysis tool more accurately flagged the disease than laryngologists did. 

“Algorithms have a larger training base,” says Dr. Anderson, who developed an app called ChatterBaby that analyzes infant cries. “We have a million samples at our disposal to train our algorithms. I don’t know if I’ve heard a million different babies crying in my life.”

So which health conditions show the most promise for voice analysis? The Voice as a Biomarker project will focus on five categories.
 

Voice disorders (cancers of the larynx, vocal fold paralysis, benign lesions on the larynx)

Obviously, vocal changes are a hallmark of these conditions, which cause things like breathiness or “roughness,” a type of vocal irregularity. Hoarseness that lasts at least 2 weeks is often one of the earliest signs of laryngeal cancer. Yet it can take months – one study found 16 weeks was the average – for patients to see a doctor after noticing the changes. Even then, laryngologists still misdiagnosed some cases of cancer when relying on vocal cues alone.

Now imagine a different scenario: The patient speaks into a smartphone app. An algorithm compares the vocal sample with the voices of laryngeal cancer patients. The app spits out the estimated odds of laryngeal cancer, helping providers decide whether to offer the patient specialist care.

Or consider spasmodic dysphonia, a neurological voice disorder that triggers spasms in the muscles of the voice box, causing a strained or breathy voice. Doctors who lack experience with vocal disorders may miss the condition. This is why diagnosis takes an average of nearly 4.5 years, according to a study in the Journal of Voice, and may include everything from allergy testing to psychiatric evaluation, says Dr. Powell. Artificial intelligence technology trained to recognize the disorder could help eliminate such unnecessary testing.
 

Neurological and neurodegenerative disorders (Alzheimer’s, Parkinson’s, stroke, ALS) 

For Alzheimer’s and Parkinson’s, “one of the first changes that’s notable is voice,” usually appearing before a formal diagnosis, says Anais Rameau, MD, an assistant professor of laryngology at Weill Cornell Medicine, New York, and another member of the NIH project. Parkinson’s may soften the voice or make it sound monotone, while Alzheimer’s disease may change the content of speech, leading to an uptick in “umms” and a preference for pronouns over nouns.

With Parkinson’s, vocal changes can occur decades before movement is affected. If doctors could detect the disease at this stage, before tremor emerged, they might be able to flag patients for early intervention, says Max Little, PhD, project director for the Parkinson’s Voice Initiative. “That is the ‘holy grail’ for finding an eventual cure.”

Again, the smartphone shows potential. In a 2022 Australian study, an AI-powered app was able to identify people with Parkinson’s based on brief voice recordings, although the sample size was small. On a larger scale, the Parkinson’s Voice Initiative collected some 17,000 samples from people across the world. “The aim was to remotely detect those with the condition using a telephone call,” says Dr. Little. It did so with about 65% accuracy. “While this is not accurate enough for clinical use, it shows the potential of the idea,” he says.

Dr. Rudzicz worked on the team behind Winterlight, an iPad app that analyzes 550 features of speech to detect dementia and Alzheimer’s (as well as mental illness). “We deployed it in long-term care facilities,” he says, identifying patients who need further review of their mental skills. Stroke is another area of interest, because slurred speech is a highly subjective measure, says Dr. Anderson. AI technology could provide a more objective evaluation.
 

Mood and psychiatric disorders (depression, schizophrenia, bipolar disorders)

No established biomarkers exist for diagnosing depression. Yet if you’re feeling down, there’s a good chance your friends can tell – even over the phone.

“We carry a lot of our mood in our voice,” says Dr. Powell. Bipolar disorder can also alter voice, making it louder and faster during manic periods, then slower and quieter during depressive bouts. The catatonic stage of schizophrenia often comes with “a very monotone, robotic voice,” says Dr. Anderson. “These are all something an algorithm can measure.”

Apps are already being used – often in research settings – to monitor voices during phone calls, analyzing rate, rhythm, volume, and pitch, to predict mood changes. For example, the PRIORI project at the University of Michigan is working on a smartphone app to identify mood changes in people with bipolar disorder, especially shifts that could increase suicide risk.

The content of speech may also offer clues. In a University of California, Los Angeles, study published in the journal PLoS One, people with mental illnesses answered computer-programmed questions (like “How have you been over the past few days?”) over the phone. An app analyzed their word choices, paying attention to how they changed over time. The researchers found that AI analysis of mood aligned well with doctors’ assessments and that some people in the study actually felt more comfortable talking to a computer.
 

Respiratory disorders (pneumonia, COPD)

Beyond talking, respiratory sounds like gasping or coughing may point to specific conditions. “Emphysema cough is different, COPD cough is different,” says Dr. Bensoussan. Researchers are trying to find out if COVID-19 has a distinct cough.

Breathing sounds can also serve as signposts. “There are different sounds when we can’t breathe,” says Dr. Bensoussan. One is called stridor, a high-pitched wheezing often resulting from a blocked airway. “I see tons of people [with stridor] misdiagnosed for years – they’ve been told they have asthma, but they don’t,” says Dr. Bensoussan. AI analysis of these sounds could help doctors more quickly identify respiratory disorders.
 

Pediatric voice and speech disorders (speech and language delays, autism)

Babies who later have autism cry differently as early as 6 months of age, which means an app like ChatterBaby could help flag children for early intervention, says Dr. Anderson. Autism is linked to several other diagnoses, such as epilepsy and sleep disorders. So analyzing an infant’s cry could prompt pediatricians to screen for a range of conditions.

ChatterBaby has been “incredibly accurate” in identifying when babies are in pain, says Dr. Anderson, because pain increases muscle tension, resulting in a louder, more energetic cry. The next goal: “We’re collecting voices from babies around the world,” she says, and then tracking those children for 7 years, looking to see if early vocal signs could predict developmental disorders. Vocal samples from young children could serve a similar purpose.
 

And that’s only the beginning

Eventually, AI technology may pick up disease-related voice changes that we can’t even hear. In a new Mayo Clinic study, certain vocal features detectable by AI – but not by the human ear – were linked to a three-fold increase in the likelihood of having plaque buildup in the arteries.

“Voice is a huge spectrum of vibrations,” explains study author Amir Lerman, MD. “We hear a very narrow range.” 

The researchers aren’t sure why heart disease alters voice, but the autonomic nervous system may play a role, because it regulates the voice box as well as blood pressure and heart rate. Dr. Lerman says other conditions, like diseases of the nerves and gut, may similarly alter the voice. Beyond patient screening, this discovery could help doctors adjust medication doses remotely, in line with these inaudible vocal signals.

“Hopefully, in the next few years, this is going to come to practice,” says Dr. Lerman.

Still, in the face of that hope, privacy concerns remain. Voice is an identifier that’s protected by the federal Health Insurance Portability and Accountability Act, which requires privacy of personal health information. That is a major reason why no large voice databases exist yet, says Dr. Bensoussan. (This makes collecting samples from children especially challenging.) Perhaps more concerning is the potential for diagnosing disease based on voice alone. “You could use that tool on anyone, including officials like the president,” says Dr. Rameau.

But the primary hurdle is the ethical sourcing of data to ensure a diversity of vocal samples. For the Voice as a Biomarker project, the researchers will establish voice quotas for different races and ethnicities, ensuring algorithms can accurately analyze a range of accents. Data from people with speech impediments will also be gathered.

Despite these challenges, researchers are optimistic. “Vocal analysis is going to be a great equalizer and improve health outcomes,” predicts Dr. Anderson. “I’m really happy that we are beginning to understand the strength of the voice.”

A version of this article first appeared on WebMD.com.

Most of us have two voice changes in our lifetime: First during puberty, as the vocal cords thicken and the voice box migrates down the throat. Then a second time as aging causes structural changes that may weaken the voice.

But for some of us, there’s another voice shift, when a disease begins or when our mental health declines.

This is why more doctors are looking into voice as a biomarker – something that tells you that a disease is present.

Vital signs like blood pressure or heart rate “can give a general idea of how sick we are. But they’re not specific to certain diseases,” says Yael Bensoussan, MD, director of the University of South Florida, Tampa’s Health Voice Center and the coprincipal investigator for the National Institutes of Health’s Voice as a Biomarker of Health project.

“We’re learning that there are patterns” in voice changes that can indicate a range of conditions, including diseases of the nervous system and mental illnesses, she says.

Speaking is complicated, involving everything from the lungs and voice box to the mouth and brain. “A breakdown in any of those parts can affect the voice,” says Maria Powell, PhD, an assistant professor of otolaryngology (the study of diseases of the ear and throat) at Vanderbilt University, Nashville, Tenn., who is working on the NIH project.

You or those around you may not notice the changes. But researchers say voice analysis as a standard part of patient care – akin to blood pressure checks or cholesterol tests – could help identify those who need medical attention earlier.

Often, all it takes is a smartphone – “something that’s cheap, off-the-shelf, and that everyone can use,” says Ariana Anderson, PhD, director of the University of California, Los Angeles, Laboratory of Computational Neuropsychology.

“You can provide voice data in your pajamas, on your couch,” says Frank Rudzicz, PhD, a computer scientist for the NIH project. “It doesn’t require very complicated or expensive equipment, and it doesn’t require a lot of expertise to obtain.” Plus, multiple samples can be collected over time, giving a more accurate picture of health than a single snapshot from, say, a cognitive test.

Over the next 4 years, the Voice as a Biomarker team will receive nearly $18 million to gather a massive amount of voice data. The goal is 20,000-30,000 samples, along with health data about each person being studied. The result will be a sprawling database scientists can use to develop algorithms linking health conditions to the way we speak.

For the first 2 years, new data will be collected exclusively via universities and high-volume clinics to control quality and accuracy. Eventually, people will be invited to submit their own voice recordings, creating a crowdsourced dataset. “Google, Alexa, Amazon – they have access to tons of voice data,” says Dr. Bensoussan. “But it’s not usable in a clinical way, because they don’t have the health information.”

Dr. Bensoussan and her colleagues hope to fill that void with advance voice screening apps, which could prove especially valuable in remote communities that lack access to specialists or as a tool for telemedicine. Down the line, wearable devices with voice analysis could alert people with chronic conditions when they need to see a doctor.

“The watch says, ‘I’ve analyzed your breathing and coughing, and today, you’re really not doing well. You should go to the hospital,’ ” says Dr. Bensoussan, envisioning a wearable for patients with COPD. “It could tell people early that things are declining.”

Artificial intelligence may be better than a brain at pinpointing the right disease. For example, slurred speech could indicate Parkinson’s, a stroke, or ALS, among other things.

“We can hold approximately seven pieces of information in our head at one time,” says Dr. Rudzicz. “It’s really hard for us to get a holistic picture using dozens or hundreds of variables at once.” But a computer can consider a whole range of vocal markers at the same time, piecing them together for a more accurate assessment.

“The goal is not to outperform a ... clinician,” says Dr. Bensoussan. Yet the potential is unmistakably there: In a recent study of patients with cancer of the larynx, an automated voice analysis tool more accurately flagged the disease than laryngologists did. 

“Algorithms have a larger training base,” says Dr. Anderson, who developed an app called ChatterBaby that analyzes infant cries. “We have a million samples at our disposal to train our algorithms. I don’t know if I’ve heard a million different babies crying in my life.”

So which health conditions show the most promise for voice analysis? The Voice as a Biomarker project will focus on five categories.
 

Voice disorders (cancers of the larynx, vocal fold paralysis, benign lesions on the larynx)

Obviously, vocal changes are a hallmark of these conditions, which cause things like breathiness or “roughness,” a type of vocal irregularity. Hoarseness that lasts at least 2 weeks is often one of the earliest signs of laryngeal cancer. Yet it can take months – one study found 16 weeks was the average – for patients to see a doctor after noticing the changes. Even then, laryngologists still misdiagnosed some cases of cancer when relying on vocal cues alone.

Now imagine a different scenario: The patient speaks into a smartphone app. An algorithm compares the vocal sample with the voices of laryngeal cancer patients. The app spits out the estimated odds of laryngeal cancer, helping providers decide whether to offer the patient specialist care.

Or consider spasmodic dysphonia, a neurological voice disorder that triggers spasms in the muscles of the voice box, causing a strained or breathy voice. Doctors who lack experience with vocal disorders may miss the condition. This is why diagnosis takes an average of nearly 4.5 years, according to a study in the Journal of Voice, and may include everything from allergy testing to psychiatric evaluation, says Dr. Powell. Artificial intelligence technology trained to recognize the disorder could help eliminate such unnecessary testing.
 

Neurological and neurodegenerative disorders (Alzheimer’s, Parkinson’s, stroke, ALS) 

For Alzheimer’s and Parkinson’s, “one of the first changes that’s notable is voice,” usually appearing before a formal diagnosis, says Anais Rameau, MD, an assistant professor of laryngology at Weill Cornell Medicine, New York, and another member of the NIH project. Parkinson’s may soften the voice or make it sound monotone, while Alzheimer’s disease may change the content of speech, leading to an uptick in “umms” and a preference for pronouns over nouns.

With Parkinson’s, vocal changes can occur decades before movement is affected. If doctors could detect the disease at this stage, before tremor emerged, they might be able to flag patients for early intervention, says Max Little, PhD, project director for the Parkinson’s Voice Initiative. “That is the ‘holy grail’ for finding an eventual cure.”

Again, the smartphone shows potential. In a 2022 Australian study, an AI-powered app was able to identify people with Parkinson’s based on brief voice recordings, although the sample size was small. On a larger scale, the Parkinson’s Voice Initiative collected some 17,000 samples from people across the world. “The aim was to remotely detect those with the condition using a telephone call,” says Dr. Little. It did so with about 65% accuracy. “While this is not accurate enough for clinical use, it shows the potential of the idea,” he says.

Dr. Rudzicz worked on the team behind Winterlight, an iPad app that analyzes 550 features of speech to detect dementia and Alzheimer’s (as well as mental illness). “We deployed it in long-term care facilities,” he says, identifying patients who need further review of their mental skills. Stroke is another area of interest, because slurred speech is a highly subjective measure, says Dr. Anderson. AI technology could provide a more objective evaluation.
 

Mood and psychiatric disorders (depression, schizophrenia, bipolar disorders)

No established biomarkers exist for diagnosing depression. Yet if you’re feeling down, there’s a good chance your friends can tell – even over the phone.

“We carry a lot of our mood in our voice,” says Dr. Powell. Bipolar disorder can also alter voice, making it louder and faster during manic periods, then slower and quieter during depressive bouts. The catatonic stage of schizophrenia often comes with “a very monotone, robotic voice,” says Dr. Anderson. “These are all something an algorithm can measure.”

Apps are already being used – often in research settings – to monitor voices during phone calls, analyzing rate, rhythm, volume, and pitch, to predict mood changes. For example, the PRIORI project at the University of Michigan is working on a smartphone app to identify mood changes in people with bipolar disorder, especially shifts that could increase suicide risk.

The content of speech may also offer clues. In a University of California, Los Angeles, study published in the journal PLoS One, people with mental illnesses answered computer-programmed questions (like “How have you been over the past few days?”) over the phone. An app analyzed their word choices, paying attention to how they changed over time. The researchers found that AI analysis of mood aligned well with doctors’ assessments and that some people in the study actually felt more comfortable talking to a computer.
 

Respiratory disorders (pneumonia, COPD)

Beyond talking, respiratory sounds like gasping or coughing may point to specific conditions. “Emphysema cough is different, COPD cough is different,” says Dr. Bensoussan. Researchers are trying to find out if COVID-19 has a distinct cough.

Breathing sounds can also serve as signposts. “There are different sounds when we can’t breathe,” says Dr. Bensoussan. One is called stridor, a high-pitched wheezing often resulting from a blocked airway. “I see tons of people [with stridor] misdiagnosed for years – they’ve been told they have asthma, but they don’t,” says Dr. Bensoussan. AI analysis of these sounds could help doctors more quickly identify respiratory disorders.
 

Pediatric voice and speech disorders (speech and language delays, autism)

Babies who later have autism cry differently as early as 6 months of age, which means an app like ChatterBaby could help flag children for early intervention, says Dr. Anderson. Autism is linked to several other diagnoses, such as epilepsy and sleep disorders. So analyzing an infant’s cry could prompt pediatricians to screen for a range of conditions.

ChatterBaby has been “incredibly accurate” in identifying when babies are in pain, says Dr. Anderson, because pain increases muscle tension, resulting in a louder, more energetic cry. The next goal: “We’re collecting voices from babies around the world,” she says, and then tracking those children for 7 years, looking to see if early vocal signs could predict developmental disorders. Vocal samples from young children could serve a similar purpose.
 

And that’s only the beginning

Eventually, AI technology may pick up disease-related voice changes that we can’t even hear. In a new Mayo Clinic study, certain vocal features detectable by AI – but not by the human ear – were linked to a three-fold increase in the likelihood of having plaque buildup in the arteries.

“Voice is a huge spectrum of vibrations,” explains study author Amir Lerman, MD. “We hear a very narrow range.” 

The researchers aren’t sure why heart disease alters voice, but the autonomic nervous system may play a role, because it regulates the voice box as well as blood pressure and heart rate. Dr. Lerman says other conditions, like diseases of the nerves and gut, may similarly alter the voice. Beyond patient screening, this discovery could help doctors adjust medication doses remotely, in line with these inaudible vocal signals.

“Hopefully, in the next few years, this is going to come to practice,” says Dr. Lerman.

Still, in the face of that hope, privacy concerns remain. Voice is an identifier that’s protected by the federal Health Insurance Portability and Accountability Act, which requires privacy of personal health information. That is a major reason why no large voice databases exist yet, says Dr. Bensoussan. (This makes collecting samples from children especially challenging.) Perhaps more concerning is the potential for diagnosing disease based on voice alone. “You could use that tool on anyone, including officials like the president,” says Dr. Rameau.

But the primary hurdle is the ethical sourcing of data to ensure a diversity of vocal samples. For the Voice as a Biomarker project, the researchers will establish voice quotas for different races and ethnicities, ensuring algorithms can accurately analyze a range of accents. Data from people with speech impediments will also be gathered.

Despite these challenges, researchers are optimistic. “Vocal analysis is going to be a great equalizer and improve health outcomes,” predicts Dr. Anderson. “I’m really happy that we are beginning to understand the strength of the voice.”

A version of this article first appeared on WebMD.com.

Most of us have two voice changes in our lifetime: First during puberty, as the vocal cords thicken and the voice box migrates down the throat. Then a second time as aging causes structural changes that may weaken the voice.

But for some of us, there’s another voice shift, when a disease begins or when our mental health declines.

This is why more doctors are looking into voice as a biomarker – something that tells you that a disease is present.

Vital signs like blood pressure or heart rate “can give a general idea of how sick we are. But they’re not specific to certain diseases,” says Yael Bensoussan, MD, director of the University of South Florida, Tampa’s Health Voice Center and the coprincipal investigator for the National Institutes of Health’s Voice as a Biomarker of Health project.

“We’re learning that there are patterns” in voice changes that can indicate a range of conditions, including diseases of the nervous system and mental illnesses, she says.

Speaking is complicated, involving everything from the lungs and voice box to the mouth and brain. “A breakdown in any of those parts can affect the voice,” says Maria Powell, PhD, an assistant professor of otolaryngology (the study of diseases of the ear and throat) at Vanderbilt University, Nashville, Tenn., who is working on the NIH project.

You or those around you may not notice the changes. But researchers say voice analysis as a standard part of patient care – akin to blood pressure checks or cholesterol tests – could help identify those who need medical attention earlier.

Often, all it takes is a smartphone – “something that’s cheap, off-the-shelf, and that everyone can use,” says Ariana Anderson, PhD, director of the University of California, Los Angeles, Laboratory of Computational Neuropsychology.

“You can provide voice data in your pajamas, on your couch,” says Frank Rudzicz, PhD, a computer scientist for the NIH project. “It doesn’t require very complicated or expensive equipment, and it doesn’t require a lot of expertise to obtain.” Plus, multiple samples can be collected over time, giving a more accurate picture of health than a single snapshot from, say, a cognitive test.

Over the next 4 years, the Voice as a Biomarker team will receive nearly $18 million to gather a massive amount of voice data. The goal is 20,000-30,000 samples, along with health data about each person being studied. The result will be a sprawling database scientists can use to develop algorithms linking health conditions to the way we speak.

For the first 2 years, new data will be collected exclusively via universities and high-volume clinics to control quality and accuracy. Eventually, people will be invited to submit their own voice recordings, creating a crowdsourced dataset. “Google, Alexa, Amazon – they have access to tons of voice data,” says Dr. Bensoussan. “But it’s not usable in a clinical way, because they don’t have the health information.”

Dr. Bensoussan and her colleagues hope to fill that void with advance voice screening apps, which could prove especially valuable in remote communities that lack access to specialists or as a tool for telemedicine. Down the line, wearable devices with voice analysis could alert people with chronic conditions when they need to see a doctor.

“The watch says, ‘I’ve analyzed your breathing and coughing, and today, you’re really not doing well. You should go to the hospital,’ ” says Dr. Bensoussan, envisioning a wearable for patients with COPD. “It could tell people early that things are declining.”

Artificial intelligence may be better than a brain at pinpointing the right disease. For example, slurred speech could indicate Parkinson’s, a stroke, or ALS, among other things.

“We can hold approximately seven pieces of information in our head at one time,” says Dr. Rudzicz. “It’s really hard for us to get a holistic picture using dozens or hundreds of variables at once.” But a computer can consider a whole range of vocal markers at the same time, piecing them together for a more accurate assessment.

“The goal is not to outperform a ... clinician,” says Dr. Bensoussan. Yet the potential is unmistakably there: In a recent study of patients with cancer of the larynx, an automated voice analysis tool more accurately flagged the disease than laryngologists did. 

“Algorithms have a larger training base,” says Dr. Anderson, who developed an app called ChatterBaby that analyzes infant cries. “We have a million samples at our disposal to train our algorithms. I don’t know if I’ve heard a million different babies crying in my life.”

So which health conditions show the most promise for voice analysis? The Voice as a Biomarker project will focus on five categories.
 

Voice disorders (cancers of the larynx, vocal fold paralysis, benign lesions on the larynx)

Obviously, vocal changes are a hallmark of these conditions, which cause things like breathiness or “roughness,” a type of vocal irregularity. Hoarseness that lasts at least 2 weeks is often one of the earliest signs of laryngeal cancer. Yet it can take months – one study found 16 weeks was the average – for patients to see a doctor after noticing the changes. Even then, laryngologists still misdiagnosed some cases of cancer when relying on vocal cues alone.

Now imagine a different scenario: The patient speaks into a smartphone app. An algorithm compares the vocal sample with the voices of laryngeal cancer patients. The app spits out the estimated odds of laryngeal cancer, helping providers decide whether to offer the patient specialist care.

Or consider spasmodic dysphonia, a neurological voice disorder that triggers spasms in the muscles of the voice box, causing a strained or breathy voice. Doctors who lack experience with vocal disorders may miss the condition. This is why diagnosis takes an average of nearly 4.5 years, according to a study in the Journal of Voice, and may include everything from allergy testing to psychiatric evaluation, says Dr. Powell. Artificial intelligence technology trained to recognize the disorder could help eliminate such unnecessary testing.
 

Neurological and neurodegenerative disorders (Alzheimer’s, Parkinson’s, stroke, ALS) 

For Alzheimer’s and Parkinson’s, “one of the first changes that’s notable is voice,” usually appearing before a formal diagnosis, says Anais Rameau, MD, an assistant professor of laryngology at Weill Cornell Medicine, New York, and another member of the NIH project. Parkinson’s may soften the voice or make it sound monotone, while Alzheimer’s disease may change the content of speech, leading to an uptick in “umms” and a preference for pronouns over nouns.

With Parkinson’s, vocal changes can occur decades before movement is affected. If doctors could detect the disease at this stage, before tremor emerged, they might be able to flag patients for early intervention, says Max Little, PhD, project director for the Parkinson’s Voice Initiative. “That is the ‘holy grail’ for finding an eventual cure.”

Again, the smartphone shows potential. In a 2022 Australian study, an AI-powered app was able to identify people with Parkinson’s based on brief voice recordings, although the sample size was small. On a larger scale, the Parkinson’s Voice Initiative collected some 17,000 samples from people across the world. “The aim was to remotely detect those with the condition using a telephone call,” says Dr. Little. It did so with about 65% accuracy. “While this is not accurate enough for clinical use, it shows the potential of the idea,” he says.

Dr. Rudzicz worked on the team behind Winterlight, an iPad app that analyzes 550 features of speech to detect dementia and Alzheimer’s (as well as mental illness). “We deployed it in long-term care facilities,” he says, identifying patients who need further review of their mental skills. Stroke is another area of interest, because slurred speech is a highly subjective measure, says Dr. Anderson. AI technology could provide a more objective evaluation.
 

Mood and psychiatric disorders (depression, schizophrenia, bipolar disorders)

No established biomarkers exist for diagnosing depression. Yet if you’re feeling down, there’s a good chance your friends can tell – even over the phone.

“We carry a lot of our mood in our voice,” says Dr. Powell. Bipolar disorder can also alter voice, making it louder and faster during manic periods, then slower and quieter during depressive bouts. The catatonic stage of schizophrenia often comes with “a very monotone, robotic voice,” says Dr. Anderson. “These are all something an algorithm can measure.”

Apps are already being used – often in research settings – to monitor voices during phone calls, analyzing rate, rhythm, volume, and pitch, to predict mood changes. For example, the PRIORI project at the University of Michigan is working on a smartphone app to identify mood changes in people with bipolar disorder, especially shifts that could increase suicide risk.

The content of speech may also offer clues. In a University of California, Los Angeles, study published in the journal PLoS One, people with mental illnesses answered computer-programmed questions (like “How have you been over the past few days?”) over the phone. An app analyzed their word choices, paying attention to how they changed over time. The researchers found that AI analysis of mood aligned well with doctors’ assessments and that some people in the study actually felt more comfortable talking to a computer.
 

Respiratory disorders (pneumonia, COPD)

Beyond talking, respiratory sounds like gasping or coughing may point to specific conditions. “Emphysema cough is different, COPD cough is different,” says Dr. Bensoussan. Researchers are trying to find out if COVID-19 has a distinct cough.

Breathing sounds can also serve as signposts. “There are different sounds when we can’t breathe,” says Dr. Bensoussan. One is called stridor, a high-pitched wheezing often resulting from a blocked airway. “I see tons of people [with stridor] misdiagnosed for years – they’ve been told they have asthma, but they don’t,” says Dr. Bensoussan. AI analysis of these sounds could help doctors more quickly identify respiratory disorders.
 

Pediatric voice and speech disorders (speech and language delays, autism)

Babies who later have autism cry differently as early as 6 months of age, which means an app like ChatterBaby could help flag children for early intervention, says Dr. Anderson. Autism is linked to several other diagnoses, such as epilepsy and sleep disorders. So analyzing an infant’s cry could prompt pediatricians to screen for a range of conditions.

ChatterBaby has been “incredibly accurate” in identifying when babies are in pain, says Dr. Anderson, because pain increases muscle tension, resulting in a louder, more energetic cry. The next goal: “We’re collecting voices from babies around the world,” she says, and then tracking those children for 7 years, looking to see if early vocal signs could predict developmental disorders. Vocal samples from young children could serve a similar purpose.
 

And that’s only the beginning

Eventually, AI technology may pick up disease-related voice changes that we can’t even hear. In a new Mayo Clinic study, certain vocal features detectable by AI – but not by the human ear – were linked to a three-fold increase in the likelihood of having plaque buildup in the arteries.

“Voice is a huge spectrum of vibrations,” explains study author Amir Lerman, MD. “We hear a very narrow range.” 

The researchers aren’t sure why heart disease alters voice, but the autonomic nervous system may play a role, because it regulates the voice box as well as blood pressure and heart rate. Dr. Lerman says other conditions, like diseases of the nerves and gut, may similarly alter the voice. Beyond patient screening, this discovery could help doctors adjust medication doses remotely, in line with these inaudible vocal signals.

“Hopefully, in the next few years, this is going to come to practice,” says Dr. Lerman.

Still, in the face of that hope, privacy concerns remain. Voice is an identifier that’s protected by the federal Health Insurance Portability and Accountability Act, which requires privacy of personal health information. That is a major reason why no large voice databases exist yet, says Dr. Bensoussan. (This makes collecting samples from children especially challenging.) Perhaps more concerning is the potential for diagnosing disease based on voice alone. “You could use that tool on anyone, including officials like the president,” says Dr. Rameau.

But the primary hurdle is the ethical sourcing of data to ensure a diversity of vocal samples. For the Voice as a Biomarker project, the researchers will establish voice quotas for different races and ethnicities, ensuring algorithms can accurately analyze a range of accents. Data from people with speech impediments will also be gathered.

Despite these challenges, researchers are optimistic. “Vocal analysis is going to be a great equalizer and improve health outcomes,” predicts Dr. Anderson. “I’m really happy that we are beginning to understand the strength of the voice.”

A version of this article first appeared on WebMD.com.

It was 1970. I was in my second year of medical school. I had been up half the night preparing for a history and physical on a patient with aortic stenosis. When I arrived at the bedside, he refused to talk to me or allow me to examine him. He requested a “White doctor” instead. I can remember the hurt and embarrassment as if it were yesterday.

Coming from the Deep South, I was very familiar with racial bias, but I did not expect it at that level and in that environment. From that point on, I was anxious at each patient encounter, concerned that this might happen again. And it did several times during my residency and fellowship.

The Occupational Safety and Health Administration defines workplace violence as “any act or threat of physical violence, harassment, intimidation, or other threatening disruptive behavior that occurs at the work site. It ranges from threats and verbal abuse to physical assaults.”

There is considerable media focus on incidents of physical violence against health care workers, but when patients, their families, or visitors openly display bias and request a different doctor, nurse, or technician for nonmedical reasons, the impact is profound. This is extremely hurtful to a professional who has worked long and hard to acquire skills and expertise. And, while speech may not constitute violence in the strictest sense of the word, there is growing evidence that it can be physically harmful through its effect on the nervous system, even if no physical contact is involved.

Incidents of bias occur regularly and are clearly on the rise. In most cases the request for a different health care worker is granted to honor the rights of the patient. The healthcare worker is left alone and emotionally wounded; the healthcare institutions are complicit.

This bias is mostly racial but can also be based on religion, sexual orientation, age, disability, body size, accent, or gender.

An entire issue of the American Medical Association Journal of Ethics was devoted to this topic. From recognizing that there are limits to what clinicians should be expected to tolerate when patients’ preferences express unjust bias, the issue also explored where those limits should be placed, why, and who is obliged to enforce them.

The newly adopted Mass General Patient Code of Conduct is evidence that health care systems are beginning to recognize this problem and that such behavior will not be tolerated.

But having a zero-tolerance policy is not enough. We must have procedures in place to discourage and mitigate the impact of patient bias.

A clear definition of what constitutes a bias incident is essential. All team members must be made aware of the procedures for reporting such incidents and the chain of command for escalation. Reporting should be encouraged, and resources must be made available to impacted team members. Surveillance, monitoring, and review are also essential as is clarification on when patient preferences should be honored.

The Mayo Clinic 5 Step Plan is an excellent example of a protocol to deal with patient bias against health care workers and is based on a thoughtful analysis of what constitutes an unreasonable request for a different clinician. I’m pleased to report that my health care system (Inova Health) is developing a similar protocol.

The health care setting should be a bias-free zone for both patients and health care workers. I have been a strong advocate of patients’ rights and worked hard to guard against bias and eliminate disparities in care, but health care workers have rights as well.

We should expect to be treated with respect.

The views expressed by the author are those of the author alone and do not represent the views of the Inova Health System. Dr. Francis is a cardiologist at Inova Heart and Vascular Institute, McLean, Va. He disclosed no conflicts of interest.

A version of this article first appeared on Medscape.com.

It was 1970. I was in my second year of medical school. I had been up half the night preparing for a history and physical on a patient with aortic stenosis. When I arrived at the bedside, he refused to talk to me or allow me to examine him. He requested a “White doctor” instead. I can remember the hurt and embarrassment as if it were yesterday.

Coming from the Deep South, I was very familiar with racial bias, but I did not expect it at that level and in that environment. From that point on, I was anxious at each patient encounter, concerned that this might happen again. And it did several times during my residency and fellowship.

The Occupational Safety and Health Administration defines workplace violence as “any act or threat of physical violence, harassment, intimidation, or other threatening disruptive behavior that occurs at the work site. It ranges from threats and verbal abuse to physical assaults.”

There is considerable media focus on incidents of physical violence against health care workers, but when patients, their families, or visitors openly display bias and request a different doctor, nurse, or technician for nonmedical reasons, the impact is profound. This is extremely hurtful to a professional who has worked long and hard to acquire skills and expertise. And, while speech may not constitute violence in the strictest sense of the word, there is growing evidence that it can be physically harmful through its effect on the nervous system, even if no physical contact is involved.

Incidents of bias occur regularly and are clearly on the rise. In most cases the request for a different health care worker is granted to honor the rights of the patient. The healthcare worker is left alone and emotionally wounded; the healthcare institutions are complicit.

This bias is mostly racial but can also be based on religion, sexual orientation, age, disability, body size, accent, or gender.

An entire issue of the American Medical Association Journal of Ethics was devoted to this topic. From recognizing that there are limits to what clinicians should be expected to tolerate when patients’ preferences express unjust bias, the issue also explored where those limits should be placed, why, and who is obliged to enforce them.

The newly adopted Mass General Patient Code of Conduct is evidence that health care systems are beginning to recognize this problem and that such behavior will not be tolerated.

But having a zero-tolerance policy is not enough. We must have procedures in place to discourage and mitigate the impact of patient bias.

A clear definition of what constitutes a bias incident is essential. All team members must be made aware of the procedures for reporting such incidents and the chain of command for escalation. Reporting should be encouraged, and resources must be made available to impacted team members. Surveillance, monitoring, and review are also essential as is clarification on when patient preferences should be honored.

The Mayo Clinic 5 Step Plan is an excellent example of a protocol to deal with patient bias against health care workers and is based on a thoughtful analysis of what constitutes an unreasonable request for a different clinician. I’m pleased to report that my health care system (Inova Health) is developing a similar protocol.

The health care setting should be a bias-free zone for both patients and health care workers. I have been a strong advocate of patients’ rights and worked hard to guard against bias and eliminate disparities in care, but health care workers have rights as well.

We should expect to be treated with respect.

The views expressed by the author are those of the author alone and do not represent the views of the Inova Health System. Dr. Francis is a cardiologist at Inova Heart and Vascular Institute, McLean, Va. He disclosed no conflicts of interest.

A version of this article first appeared on Medscape.com.

It was 1970. I was in my second year of medical school. I had been up half the night preparing for a history and physical on a patient with aortic stenosis. When I arrived at the bedside, he refused to talk to me or allow me to examine him. He requested a “White doctor” instead. I can remember the hurt and embarrassment as if it were yesterday.

Coming from the Deep South, I was very familiar with racial bias, but I did not expect it at that level and in that environment. From that point on, I was anxious at each patient encounter, concerned that this might happen again. And it did several times during my residency and fellowship.

The Occupational Safety and Health Administration defines workplace violence as “any act or threat of physical violence, harassment, intimidation, or other threatening disruptive behavior that occurs at the work site. It ranges from threats and verbal abuse to physical assaults.”

There is considerable media focus on incidents of physical violence against health care workers, but when patients, their families, or visitors openly display bias and request a different doctor, nurse, or technician for nonmedical reasons, the impact is profound. This is extremely hurtful to a professional who has worked long and hard to acquire skills and expertise. And, while speech may not constitute violence in the strictest sense of the word, there is growing evidence that it can be physically harmful through its effect on the nervous system, even if no physical contact is involved.

Incidents of bias occur regularly and are clearly on the rise. In most cases the request for a different health care worker is granted to honor the rights of the patient. The healthcare worker is left alone and emotionally wounded; the healthcare institutions are complicit.

This bias is mostly racial but can also be based on religion, sexual orientation, age, disability, body size, accent, or gender.

An entire issue of the American Medical Association Journal of Ethics was devoted to this topic. From recognizing that there are limits to what clinicians should be expected to tolerate when patients’ preferences express unjust bias, the issue also explored where those limits should be placed, why, and who is obliged to enforce them.

The newly adopted Mass General Patient Code of Conduct is evidence that health care systems are beginning to recognize this problem and that such behavior will not be tolerated.

But having a zero-tolerance policy is not enough. We must have procedures in place to discourage and mitigate the impact of patient bias.

A clear definition of what constitutes a bias incident is essential. All team members must be made aware of the procedures for reporting such incidents and the chain of command for escalation. Reporting should be encouraged, and resources must be made available to impacted team members. Surveillance, monitoring, and review are also essential as is clarification on when patient preferences should be honored.

The Mayo Clinic 5 Step Plan is an excellent example of a protocol to deal with patient bias against health care workers and is based on a thoughtful analysis of what constitutes an unreasonable request for a different clinician. I’m pleased to report that my health care system (Inova Health) is developing a similar protocol.

The health care setting should be a bias-free zone for both patients and health care workers. I have been a strong advocate of patients’ rights and worked hard to guard against bias and eliminate disparities in care, but health care workers have rights as well.

We should expect to be treated with respect.

The views expressed by the author are those of the author alone and do not represent the views of the Inova Health System. Dr. Francis is a cardiologist at Inova Heart and Vascular Institute, McLean, Va. He disclosed no conflicts of interest.

A version of this article first appeared on Medscape.com.

NASHVILLE, TENN. – There is no negative impact of in utero exposure to antiseizure medications on children’s creativity, new research shows.

The results of this study, along with other research, suggest the risk for cognitive problems “is fairly low” overall for children of women with epilepsy taking lamotrigine or levetiracetam, study investigator, Kimford J. Meador, MD, professor, department of neurology & neurological sciences, Stanford (Calif.) University School of Medicine, told this news organization.

“This is another encouraging piece that’s showing these new drugs are safe with regard to cognition.”

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Capturing creativity

Fetal exposure to antiseizure medications can produce adverse neurodevelopmental effects. These are typically assessed using measures such as general intelligence, verbal/nonverbal abilities, or additional educational needs.

However, these measures don’t capture creativity, which “is related to intelligence but not completely,” said Dr. Meador. “I have seen wonderful examples of creativity in people who have a lot of cognitive impairment.”

He referred to one of his patients with epilepsy who is “spectacularly good” at painting with watercolors, even though she has significant cognitive impairment.

The new analysis is part of the MONEAD study, a prospective, observational multicenter study examining pregnancy outcomes for both mother and child. It included pregnant women who were enrolled at under 20 weeks’ gestational age.

The women with epilepsy in the study were primarily on monotherapy (73%), and of these, 82% were on lamotrigine or levetiracetam. About 22% were on polytherapy, of which 42% were on dual therapy with lamotrigine and levetiracetam.
 

Fluency, originality

Researchers assessed the children of these women at age 4½ years using the Torrance Test of Creative Thinking-Figural (TTCT-F). This is a standardized assessment of creative thinking with index scores measuring such things as fluency, originality, abstractness, and elaboration.

Dr. Meador noted the research team used a shorter version of the test battery “so as to not wear out the families and kids.”

During the test, children were given lines of different shapes and asked to draw a picture using these lines. Dr. Meador pointed out the drawings ranged from quite basic to more intricate.

One child cleverly turned a few squiggly lines into a car. “I can look at this and say this kid’s going to do very well,” said Dr. Meador.

Investigators compared scores between 241 children of women with epilepsy (WWE) and 65 children of healthy women (HW). They adjusted for the mother’s IQ, education level, age at enrollment, gestation age at enrollment, post-birth average anxiety score, and the child’s ethnicity and sex.

Investigators found the mean TTCT-F scores did not differ significantly between the two groups: adjusted least squares mean of 89.5 (95% confidence interval, 86.7-92.3) for children of WWE, compared with adjusted least square mean of 92.0 (95% CI, 86.4-97.6) for children of HW.
 

Balancing act

The researchers haven’t looked at a dose effect in this current study, but Dr. Meador said it’s always “a balancing act” between giving enough of the drug to keep mothers from seizing, which affect both the mother and fetus, and giving as low a dose as possible to protect the fetus.

In addition, as medication levels change during pregnancy, he said he recommends that drug levels are monitored monthly so that medication can be adjusted as necessary.

Looking at what factors might predict creativity scores, researchers found children did less well creatively if their mother didn’t have a college degree (estimate –9.5; 95% CI, –17.9 to –1.2; P = .025).

“It looks like being in a home where the mother has had more education is going to have an impact on the kid’s thinking and creativity,” said Dr. Meador.

These new findings are consistent with a lack of differences in other cognitive abilities that Dr. Meador and his team found when the children were younger.

“At age 3, we did not find an overall difference in cognitive and verbal abilities and intelligence between the children of mothers with epilepsy and those of healthy women,” he said.

The researchers aim to assess cognitive and behavioral outcomes in these children when they are 6 years old.
 

Helpful information

Commenting on the findings, Stéphane Auvin, MD, PhD, chair of the department of pediatric neurology at the University of Paris, who co-moderated a platform session featuring the research, said the study “is an interesting measure of the impact of being exposed to antiseizure medications.”

Creativity is “complex,” he said. “It’s not only cognition; it could be things like behavior and impulsivity.”

The new information is “very helpful.” Focusing on something broader than just IQ “gives you a better picture of what’s going on.”

The study received funding from NIH, NINDS, and NICH. Dr. Meador has received grants from NIH/NINDS, NIH/NICHD, Veterans Administration, and Eisai. He has been a consultant for Epilepsy Consortium, Novartis, Supernus, Upsher Smith Labs, and UCB Pharma. Dr. Auvin reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NASHVILLE, TENN. – There is no negative impact of in utero exposure to antiseizure medications on children’s creativity, new research shows.

The results of this study, along with other research, suggest the risk for cognitive problems “is fairly low” overall for children of women with epilepsy taking lamotrigine or levetiracetam, study investigator, Kimford J. Meador, MD, professor, department of neurology & neurological sciences, Stanford (Calif.) University School of Medicine, told this news organization.

“This is another encouraging piece that’s showing these new drugs are safe with regard to cognition.”

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Capturing creativity

Fetal exposure to antiseizure medications can produce adverse neurodevelopmental effects. These are typically assessed using measures such as general intelligence, verbal/nonverbal abilities, or additional educational needs.

However, these measures don’t capture creativity, which “is related to intelligence but not completely,” said Dr. Meador. “I have seen wonderful examples of creativity in people who have a lot of cognitive impairment.”

He referred to one of his patients with epilepsy who is “spectacularly good” at painting with watercolors, even though she has significant cognitive impairment.

The new analysis is part of the MONEAD study, a prospective, observational multicenter study examining pregnancy outcomes for both mother and child. It included pregnant women who were enrolled at under 20 weeks’ gestational age.

The women with epilepsy in the study were primarily on monotherapy (73%), and of these, 82% were on lamotrigine or levetiracetam. About 22% were on polytherapy, of which 42% were on dual therapy with lamotrigine and levetiracetam.
 

Fluency, originality

Researchers assessed the children of these women at age 4½ years using the Torrance Test of Creative Thinking-Figural (TTCT-F). This is a standardized assessment of creative thinking with index scores measuring such things as fluency, originality, abstractness, and elaboration.

Dr. Meador noted the research team used a shorter version of the test battery “so as to not wear out the families and kids.”

During the test, children were given lines of different shapes and asked to draw a picture using these lines. Dr. Meador pointed out the drawings ranged from quite basic to more intricate.

One child cleverly turned a few squiggly lines into a car. “I can look at this and say this kid’s going to do very well,” said Dr. Meador.

Investigators compared scores between 241 children of women with epilepsy (WWE) and 65 children of healthy women (HW). They adjusted for the mother’s IQ, education level, age at enrollment, gestation age at enrollment, post-birth average anxiety score, and the child’s ethnicity and sex.

Investigators found the mean TTCT-F scores did not differ significantly between the two groups: adjusted least squares mean of 89.5 (95% confidence interval, 86.7-92.3) for children of WWE, compared with adjusted least square mean of 92.0 (95% CI, 86.4-97.6) for children of HW.
 

Balancing act

The researchers haven’t looked at a dose effect in this current study, but Dr. Meador said it’s always “a balancing act” between giving enough of the drug to keep mothers from seizing, which affect both the mother and fetus, and giving as low a dose as possible to protect the fetus.

In addition, as medication levels change during pregnancy, he said he recommends that drug levels are monitored monthly so that medication can be adjusted as necessary.

Looking at what factors might predict creativity scores, researchers found children did less well creatively if their mother didn’t have a college degree (estimate –9.5; 95% CI, –17.9 to –1.2; P = .025).

“It looks like being in a home where the mother has had more education is going to have an impact on the kid’s thinking and creativity,” said Dr. Meador.

These new findings are consistent with a lack of differences in other cognitive abilities that Dr. Meador and his team found when the children were younger.

“At age 3, we did not find an overall difference in cognitive and verbal abilities and intelligence between the children of mothers with epilepsy and those of healthy women,” he said.

The researchers aim to assess cognitive and behavioral outcomes in these children when they are 6 years old.
 

Helpful information

Commenting on the findings, Stéphane Auvin, MD, PhD, chair of the department of pediatric neurology at the University of Paris, who co-moderated a platform session featuring the research, said the study “is an interesting measure of the impact of being exposed to antiseizure medications.”

Creativity is “complex,” he said. “It’s not only cognition; it could be things like behavior and impulsivity.”

The new information is “very helpful.” Focusing on something broader than just IQ “gives you a better picture of what’s going on.”

The study received funding from NIH, NINDS, and NICH. Dr. Meador has received grants from NIH/NINDS, NIH/NICHD, Veterans Administration, and Eisai. He has been a consultant for Epilepsy Consortium, Novartis, Supernus, Upsher Smith Labs, and UCB Pharma. Dr. Auvin reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NASHVILLE, TENN. – There is no negative impact of in utero exposure to antiseizure medications on children’s creativity, new research shows.

The results of this study, along with other research, suggest the risk for cognitive problems “is fairly low” overall for children of women with epilepsy taking lamotrigine or levetiracetam, study investigator, Kimford J. Meador, MD, professor, department of neurology & neurological sciences, Stanford (Calif.) University School of Medicine, told this news organization.

“This is another encouraging piece that’s showing these new drugs are safe with regard to cognition.”

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Capturing creativity

Fetal exposure to antiseizure medications can produce adverse neurodevelopmental effects. These are typically assessed using measures such as general intelligence, verbal/nonverbal abilities, or additional educational needs.

However, these measures don’t capture creativity, which “is related to intelligence but not completely,” said Dr. Meador. “I have seen wonderful examples of creativity in people who have a lot of cognitive impairment.”

He referred to one of his patients with epilepsy who is “spectacularly good” at painting with watercolors, even though she has significant cognitive impairment.

The new analysis is part of the MONEAD study, a prospective, observational multicenter study examining pregnancy outcomes for both mother and child. It included pregnant women who were enrolled at under 20 weeks’ gestational age.

The women with epilepsy in the study were primarily on monotherapy (73%), and of these, 82% were on lamotrigine or levetiracetam. About 22% were on polytherapy, of which 42% were on dual therapy with lamotrigine and levetiracetam.
 

Fluency, originality

Researchers assessed the children of these women at age 4½ years using the Torrance Test of Creative Thinking-Figural (TTCT-F). This is a standardized assessment of creative thinking with index scores measuring such things as fluency, originality, abstractness, and elaboration.

Dr. Meador noted the research team used a shorter version of the test battery “so as to not wear out the families and kids.”

During the test, children were given lines of different shapes and asked to draw a picture using these lines. Dr. Meador pointed out the drawings ranged from quite basic to more intricate.

One child cleverly turned a few squiggly lines into a car. “I can look at this and say this kid’s going to do very well,” said Dr. Meador.

Investigators compared scores between 241 children of women with epilepsy (WWE) and 65 children of healthy women (HW). They adjusted for the mother’s IQ, education level, age at enrollment, gestation age at enrollment, post-birth average anxiety score, and the child’s ethnicity and sex.

Investigators found the mean TTCT-F scores did not differ significantly between the two groups: adjusted least squares mean of 89.5 (95% confidence interval, 86.7-92.3) for children of WWE, compared with adjusted least square mean of 92.0 (95% CI, 86.4-97.6) for children of HW.
 

Balancing act

The researchers haven’t looked at a dose effect in this current study, but Dr. Meador said it’s always “a balancing act” between giving enough of the drug to keep mothers from seizing, which affect both the mother and fetus, and giving as low a dose as possible to protect the fetus.

In addition, as medication levels change during pregnancy, he said he recommends that drug levels are monitored monthly so that medication can be adjusted as necessary.

Looking at what factors might predict creativity scores, researchers found children did less well creatively if their mother didn’t have a college degree (estimate –9.5; 95% CI, –17.9 to –1.2; P = .025).

“It looks like being in a home where the mother has had more education is going to have an impact on the kid’s thinking and creativity,” said Dr. Meador.

These new findings are consistent with a lack of differences in other cognitive abilities that Dr. Meador and his team found when the children were younger.

“At age 3, we did not find an overall difference in cognitive and verbal abilities and intelligence between the children of mothers with epilepsy and those of healthy women,” he said.

The researchers aim to assess cognitive and behavioral outcomes in these children when they are 6 years old.
 

Helpful information

Commenting on the findings, Stéphane Auvin, MD, PhD, chair of the department of pediatric neurology at the University of Paris, who co-moderated a platform session featuring the research, said the study “is an interesting measure of the impact of being exposed to antiseizure medications.”

Creativity is “complex,” he said. “It’s not only cognition; it could be things like behavior and impulsivity.”

The new information is “very helpful.” Focusing on something broader than just IQ “gives you a better picture of what’s going on.”

The study received funding from NIH, NINDS, and NICH. Dr. Meador has received grants from NIH/NINDS, NIH/NICHD, Veterans Administration, and Eisai. He has been a consultant for Epilepsy Consortium, Novartis, Supernus, Upsher Smith Labs, and UCB Pharma. Dr. Auvin reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A genetic postmortem analysis of the brains of patients with schizophrenia suggests dysfunction of dopamine receptors in the caudate nucleus may cause the disorder.

Investigators identified a mechanism on the dopamine receptor, known as the autoreceptor, which regulates how much dopamine is released from the presynaptic neuron. Impairment of this autoreceptor leads to poorly controlled dopamine release and excessive dopamine flow.

The researchers found decreased expression of this autoreceptor accounts for the genetic evidence of schizophrenia risk, and, using a suite of statistical routines, they showed that this relationship is probably causative.

“Our research confirms the scientific hypothesis that too much dopamine plays a likely causative role in psychosis and precisely how this is based on genetic factors,” study investigator Daniel Weinberger, MD, director and CEO of the Lieber Institute for Brain Development, Baltimore, told this news organization.

“Drugs that treat psychosis symptoms by simply blocking dopamine receptors have harsh side effects. ... Theoretically, scientists could now develop therapies that target these malfunctioning autoreceptors to treat this devastating condition with fewer side effects,” he said.

The study was published online in Nature Neuroscience.
 

‘Privileged spot’

“Large international genetic studies known as genomewide association studies have identified hundreds of regions of the human genome housing potential risk genes for schizophrenia,” Dr. Weinberger said.

“However, these regions are still poorly resolved in terms of specific genes, and treatments and diagnostic techniques are far from what they should be.” Moreover, “treatments for schizophrenia address the symptoms of psychosis but not the cause,” he said.

“For more than 70 years, neuroscientists have suspected that dopamine plays a key role in schizophrenia, but what kind of role, exactly, has remained a mystery,” Dr. Weinberger noted. “It occupied a privileged spot in the principal hypothesis about schizophrenia for over 60 years – the so-called ‘dopamine hypothesis.’ ”

Antipsychotic drugs that reduce dopamine “are the principal medical treatments but they cause serious side effects, including an inability to experience pleasure and joy – a sad reality for patients and their families,” he continued.

The current study “set out to understand how dopamine acts in schizophrenia” using “analysis of the genetic and transcriptional landscape” of the postmortem caudate nucleus from 443 donors (245 neurotypical, 154 with schizophrenia, and 44 with bipolar disorder).

Brain samples were from individuals of diverse ancestry (210 were of African ancestry and 2,233 were of European ancestry).
 

New treatment target?

The researchers performed an analysis of transancestry expression quantitative trait loci, genetic variants that explain variations in gene expression levels, which express in the caudate, annotating “hundreds of caudate-specific cis-eQTLs.”

Then they integrated this analysis with gene expression that emerged from the latest genomewide association study and transcriptome-wide association study, identifying hundreds of genes that “showed a potential causal association with schizophrenia risk in the caudate nucleus,” including a specific isoform of the dopamine D2 receptor, which is upregulated in the caudate nucleus of those with schizophrenia.

“If autoreceptors don’t function properly the flow of dopamine in the brain is poorly controlled and too much dopamine flows for too long,” said Dr. Weinberger.

In particular, they observed “extensive differential gene expression” for schizophrenia in 2,701 genes in those with schizophrenia, compared with those without: glial cell–derived neurotrophic factor antisense RNA was a top-up gene and tyrosine hydroxylase, which is a rate-limiting enzyme in dopamine synthesis, was a down-regulated gene. Dopamine receptors DRD2 and DRD3 were differentially expressed.

Having done this, they looked at the effects of antipsychotic medications that target D2 regions on gene expression in the caudate by testing for differences between individuals with schizophrenia who were taking antipsychotics at the time of death, those not taking antipsychotics at the time of death (n = 104 and 49, respectively), and neurotypical individuals (n = 239).

There were 2,692 differentially expressed genes between individuals taking antipsychotics versus neurotypical individuals (false discovery rate < 0.05). By contrast, there were only 665 differentially expressed genes (FDR < .05) between those not taking antipsychotics and neurotypical individuals.

“We found that antipsychotic medication has an extensive influence on caudate gene expression,” the investigators noted.

They then developed a new approach to “infer gene networks from expression data.” This method is based on deep neural networks, obtaining a “low-dimensional representation of each gene’s expression across individuals.” The representation is then used to build a “gene neighborhood graph and assign genes to modules.”

This method identified “several modules enriched for genes associated with schizophrenia risk.” The expression representations captured in this approach placed genes in “biologically meaningful neighborhoods, which can provide insight into potential interactions if these genes are targeted for therapeutic intervention,” the authors summarized.

“Now that our new research has identified the specific mechanism by which dopamine plays a causative role in schizophrenia, we hope we have opened the door for more targeted drugs or diagnostic tests that could make life better for patients and their families,” Dr. Weinberger said.
 

No causal link?

Commenting on the study, Rifaat El-Mallakh, MD, director of the mood disorders research program, department of psychiatry and behavioral sciences, University of Louisville (Ky.), called it an “excellent study performed by an excellent research group” that “fills an important lacuna in our research database.”

However, Dr. El-Mallakh, who was not involved in the research, disagreed that the findings show causality. “The data that can be gleaned from this study is limited and the design has significant limitations. As with all genetic studies, this is an association study. It tells us nothing about the cause-effect relationship between the genes and the illness.

“We do not know why genes are associated with the illness. Genetic overrepresentation can have multiple causes, and more so when the data is a convenience sample. As noted by the authors, much of what they observed was probably related to medication effect. I don’t think this study specifically tells us anything clinically,” he added.

The study was supported by the LIBD, the BrainSeq Consortium, an National Institutes of Health fellowship to two of the authors, and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation to one of the authors. Dr. Weinberger has reported no relevant financial relationships. Dr. El-Mallakh declared no specific financial relationships relevant to the study but has reported being a speaker for several companies that manufacture antipsychotics.

A version of this article first appeared on Medscape.com.

A genetic postmortem analysis of the brains of patients with schizophrenia suggests dysfunction of dopamine receptors in the caudate nucleus may cause the disorder.

Investigators identified a mechanism on the dopamine receptor, known as the autoreceptor, which regulates how much dopamine is released from the presynaptic neuron. Impairment of this autoreceptor leads to poorly controlled dopamine release and excessive dopamine flow.

The researchers found decreased expression of this autoreceptor accounts for the genetic evidence of schizophrenia risk, and, using a suite of statistical routines, they showed that this relationship is probably causative.

“Our research confirms the scientific hypothesis that too much dopamine plays a likely causative role in psychosis and precisely how this is based on genetic factors,” study investigator Daniel Weinberger, MD, director and CEO of the Lieber Institute for Brain Development, Baltimore, told this news organization.

“Drugs that treat psychosis symptoms by simply blocking dopamine receptors have harsh side effects. ... Theoretically, scientists could now develop therapies that target these malfunctioning autoreceptors to treat this devastating condition with fewer side effects,” he said.

The study was published online in Nature Neuroscience.
 

‘Privileged spot’

“Large international genetic studies known as genomewide association studies have identified hundreds of regions of the human genome housing potential risk genes for schizophrenia,” Dr. Weinberger said.

“However, these regions are still poorly resolved in terms of specific genes, and treatments and diagnostic techniques are far from what they should be.” Moreover, “treatments for schizophrenia address the symptoms of psychosis but not the cause,” he said.

“For more than 70 years, neuroscientists have suspected that dopamine plays a key role in schizophrenia, but what kind of role, exactly, has remained a mystery,” Dr. Weinberger noted. “It occupied a privileged spot in the principal hypothesis about schizophrenia for over 60 years – the so-called ‘dopamine hypothesis.’ ”

Antipsychotic drugs that reduce dopamine “are the principal medical treatments but they cause serious side effects, including an inability to experience pleasure and joy – a sad reality for patients and their families,” he continued.

The current study “set out to understand how dopamine acts in schizophrenia” using “analysis of the genetic and transcriptional landscape” of the postmortem caudate nucleus from 443 donors (245 neurotypical, 154 with schizophrenia, and 44 with bipolar disorder).

Brain samples were from individuals of diverse ancestry (210 were of African ancestry and 2,233 were of European ancestry).
 

New treatment target?

The researchers performed an analysis of transancestry expression quantitative trait loci, genetic variants that explain variations in gene expression levels, which express in the caudate, annotating “hundreds of caudate-specific cis-eQTLs.”

Then they integrated this analysis with gene expression that emerged from the latest genomewide association study and transcriptome-wide association study, identifying hundreds of genes that “showed a potential causal association with schizophrenia risk in the caudate nucleus,” including a specific isoform of the dopamine D2 receptor, which is upregulated in the caudate nucleus of those with schizophrenia.

“If autoreceptors don’t function properly the flow of dopamine in the brain is poorly controlled and too much dopamine flows for too long,” said Dr. Weinberger.

In particular, they observed “extensive differential gene expression” for schizophrenia in 2,701 genes in those with schizophrenia, compared with those without: glial cell–derived neurotrophic factor antisense RNA was a top-up gene and tyrosine hydroxylase, which is a rate-limiting enzyme in dopamine synthesis, was a down-regulated gene. Dopamine receptors DRD2 and DRD3 were differentially expressed.

Having done this, they looked at the effects of antipsychotic medications that target D2 regions on gene expression in the caudate by testing for differences between individuals with schizophrenia who were taking antipsychotics at the time of death, those not taking antipsychotics at the time of death (n = 104 and 49, respectively), and neurotypical individuals (n = 239).

There were 2,692 differentially expressed genes between individuals taking antipsychotics versus neurotypical individuals (false discovery rate < 0.05). By contrast, there were only 665 differentially expressed genes (FDR < .05) between those not taking antipsychotics and neurotypical individuals.

“We found that antipsychotic medication has an extensive influence on caudate gene expression,” the investigators noted.

They then developed a new approach to “infer gene networks from expression data.” This method is based on deep neural networks, obtaining a “low-dimensional representation of each gene’s expression across individuals.” The representation is then used to build a “gene neighborhood graph and assign genes to modules.”

This method identified “several modules enriched for genes associated with schizophrenia risk.” The expression representations captured in this approach placed genes in “biologically meaningful neighborhoods, which can provide insight into potential interactions if these genes are targeted for therapeutic intervention,” the authors summarized.

“Now that our new research has identified the specific mechanism by which dopamine plays a causative role in schizophrenia, we hope we have opened the door for more targeted drugs or diagnostic tests that could make life better for patients and their families,” Dr. Weinberger said.
 

No causal link?

Commenting on the study, Rifaat El-Mallakh, MD, director of the mood disorders research program, department of psychiatry and behavioral sciences, University of Louisville (Ky.), called it an “excellent study performed by an excellent research group” that “fills an important lacuna in our research database.”

However, Dr. El-Mallakh, who was not involved in the research, disagreed that the findings show causality. “The data that can be gleaned from this study is limited and the design has significant limitations. As with all genetic studies, this is an association study. It tells us nothing about the cause-effect relationship between the genes and the illness.

“We do not know why genes are associated with the illness. Genetic overrepresentation can have multiple causes, and more so when the data is a convenience sample. As noted by the authors, much of what they observed was probably related to medication effect. I don’t think this study specifically tells us anything clinically,” he added.

The study was supported by the LIBD, the BrainSeq Consortium, an National Institutes of Health fellowship to two of the authors, and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation to one of the authors. Dr. Weinberger has reported no relevant financial relationships. Dr. El-Mallakh declared no specific financial relationships relevant to the study but has reported being a speaker for several companies that manufacture antipsychotics.

A version of this article first appeared on Medscape.com.

A genetic postmortem analysis of the brains of patients with schizophrenia suggests dysfunction of dopamine receptors in the caudate nucleus may cause the disorder.

Investigators identified a mechanism on the dopamine receptor, known as the autoreceptor, which regulates how much dopamine is released from the presynaptic neuron. Impairment of this autoreceptor leads to poorly controlled dopamine release and excessive dopamine flow.

The researchers found decreased expression of this autoreceptor accounts for the genetic evidence of schizophrenia risk, and, using a suite of statistical routines, they showed that this relationship is probably causative.

“Our research confirms the scientific hypothesis that too much dopamine plays a likely causative role in psychosis and precisely how this is based on genetic factors,” study investigator Daniel Weinberger, MD, director and CEO of the Lieber Institute for Brain Development, Baltimore, told this news organization.

“Drugs that treat psychosis symptoms by simply blocking dopamine receptors have harsh side effects. ... Theoretically, scientists could now develop therapies that target these malfunctioning autoreceptors to treat this devastating condition with fewer side effects,” he said.

The study was published online in Nature Neuroscience.
 

‘Privileged spot’

“Large international genetic studies known as genomewide association studies have identified hundreds of regions of the human genome housing potential risk genes for schizophrenia,” Dr. Weinberger said.

“However, these regions are still poorly resolved in terms of specific genes, and treatments and diagnostic techniques are far from what they should be.” Moreover, “treatments for schizophrenia address the symptoms of psychosis but not the cause,” he said.

“For more than 70 years, neuroscientists have suspected that dopamine plays a key role in schizophrenia, but what kind of role, exactly, has remained a mystery,” Dr. Weinberger noted. “It occupied a privileged spot in the principal hypothesis about schizophrenia for over 60 years – the so-called ‘dopamine hypothesis.’ ”

Antipsychotic drugs that reduce dopamine “are the principal medical treatments but they cause serious side effects, including an inability to experience pleasure and joy – a sad reality for patients and their families,” he continued.

The current study “set out to understand how dopamine acts in schizophrenia” using “analysis of the genetic and transcriptional landscape” of the postmortem caudate nucleus from 443 donors (245 neurotypical, 154 with schizophrenia, and 44 with bipolar disorder).

Brain samples were from individuals of diverse ancestry (210 were of African ancestry and 2,233 were of European ancestry).
 

New treatment target?

The researchers performed an analysis of transancestry expression quantitative trait loci, genetic variants that explain variations in gene expression levels, which express in the caudate, annotating “hundreds of caudate-specific cis-eQTLs.”

Then they integrated this analysis with gene expression that emerged from the latest genomewide association study and transcriptome-wide association study, identifying hundreds of genes that “showed a potential causal association with schizophrenia risk in the caudate nucleus,” including a specific isoform of the dopamine D2 receptor, which is upregulated in the caudate nucleus of those with schizophrenia.

“If autoreceptors don’t function properly the flow of dopamine in the brain is poorly controlled and too much dopamine flows for too long,” said Dr. Weinberger.

In particular, they observed “extensive differential gene expression” for schizophrenia in 2,701 genes in those with schizophrenia, compared with those without: glial cell–derived neurotrophic factor antisense RNA was a top-up gene and tyrosine hydroxylase, which is a rate-limiting enzyme in dopamine synthesis, was a down-regulated gene. Dopamine receptors DRD2 and DRD3 were differentially expressed.

Having done this, they looked at the effects of antipsychotic medications that target D2 regions on gene expression in the caudate by testing for differences between individuals with schizophrenia who were taking antipsychotics at the time of death, those not taking antipsychotics at the time of death (n = 104 and 49, respectively), and neurotypical individuals (n = 239).

There were 2,692 differentially expressed genes between individuals taking antipsychotics versus neurotypical individuals (false discovery rate < 0.05). By contrast, there were only 665 differentially expressed genes (FDR < .05) between those not taking antipsychotics and neurotypical individuals.

“We found that antipsychotic medication has an extensive influence on caudate gene expression,” the investigators noted.

They then developed a new approach to “infer gene networks from expression data.” This method is based on deep neural networks, obtaining a “low-dimensional representation of each gene’s expression across individuals.” The representation is then used to build a “gene neighborhood graph and assign genes to modules.”

This method identified “several modules enriched for genes associated with schizophrenia risk.” The expression representations captured in this approach placed genes in “biologically meaningful neighborhoods, which can provide insight into potential interactions if these genes are targeted for therapeutic intervention,” the authors summarized.

“Now that our new research has identified the specific mechanism by which dopamine plays a causative role in schizophrenia, we hope we have opened the door for more targeted drugs or diagnostic tests that could make life better for patients and their families,” Dr. Weinberger said.
 

No causal link?

Commenting on the study, Rifaat El-Mallakh, MD, director of the mood disorders research program, department of psychiatry and behavioral sciences, University of Louisville (Ky.), called it an “excellent study performed by an excellent research group” that “fills an important lacuna in our research database.”

However, Dr. El-Mallakh, who was not involved in the research, disagreed that the findings show causality. “The data that can be gleaned from this study is limited and the design has significant limitations. As with all genetic studies, this is an association study. It tells us nothing about the cause-effect relationship between the genes and the illness.

“We do not know why genes are associated with the illness. Genetic overrepresentation can have multiple causes, and more so when the data is a convenience sample. As noted by the authors, much of what they observed was probably related to medication effect. I don’t think this study specifically tells us anything clinically,” he added.

The study was supported by the LIBD, the BrainSeq Consortium, an National Institutes of Health fellowship to two of the authors, and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation to one of the authors. Dr. Weinberger has reported no relevant financial relationships. Dr. El-Mallakh declared no specific financial relationships relevant to the study but has reported being a speaker for several companies that manufacture antipsychotics.

A version of this article first appeared on Medscape.com.