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COVID-19 tied to acceleration of Alzheimer’s disease pathology
, a new study shows.
These results suggest that COVID-19 may accelerate Alzheimer’s disease symptoms and pathology, said study investigator Thomas Wisniewski, MD, professor of neurology, pathology, and psychiatry at New York University.
The findings were presented here at the Alzheimer’s Association International Conference (AAIC) 2021.
Strong correlation
There’s a clear association between SARS-CoV-2 infection and Alzheimer’s disease-related dementia. Patients with Alzheimer’s disease are at threefold higher risk for the infection and have a twofold higher risk for death, Dr. Wisniewski told meeting delegates.
He and his colleagues conducted a prospective study of patients who had tested positive for SARS-CoV-2 and who experienced neurologic sequelae and SARS-CoV-2 patients who were without neurologic sequelae. All patients were hospitalized from March 10 to May 20, 2020. This was during a period when New York City was overwhelmed by COVID: About 35% of hospitalized patients had COVID.
Of those who experienced neurologic events, the most common “by far and away” (51%) was toxic metabolic encephalopathy (TME), said Dr. Wisniewski. Other associations included seizures, hypoxic/anoxic injury, and ischemic stroke.
The most common TMEs were septic and hypoxic ischemia. In most patients (78%), TME had more than one cause.
Researchers followed 196 patients with COVID and neurologic complications (case patients) and 186 matched control patients who had no neurologic complications over a period of 6 months.
“Unfortunately, both groups had poor outcomes,” said Dr. Wisniewski. About 50% had impaired cognition, and 56% experienced limitations in activities of daily living.
However, those patients with COVID-19 who had neurologic sequelae “fared even worse,” said Dr. Wisniewski. Compared with control patients, they had twofold worse Modified Rankin Scale scores and worse scores on activity of daily living, and they were much less likely to return to work.
Mechanisms by which COVID-19 affects longer-term cognitive dysfunction are unclear, but inflammation likely plays a role.
The research team compared a number of Alzheimer’s disease plasma biomarkers in 158 patients with COVID-19 who had neurologic symptoms and 152 COVID patients with COVID but no neurologic symptoms. They found marked elevations of neurofilament light, a marker of neuronal injury, in those with symptoms (P = .0003) as well as increased glial fibrillary acid protein, a marker of neuroinflammation (P = .0098).
Ubiquitin carboxyl-terminal hydrolase L1, another marker of neuronal injury, was also elevated in those with neurologic symptoms. Regarding Alzheimer’s disease pathology, total tau (t-tau) and phosphorylated tau “also tracked with neurological sequelae,” said Dr. Wisniewski.
There was no difference in levels of amyloid beta 40 (A beta 40) between groups. However, A beta 42 plasma levels were significantly lower in those with neurologic effects, suggesting higher levels in the brain. In addition, the ratio of t-tau to A beta 42 “clearly differentiated the two groups,” he said.
“Serum biomarkers of neuroinflammation and neuronal injury and Alzheimer’s disease correlate strongly, perhaps suggesting that folks with COVID infection and neurological sequelae may have an acceleration of Alzheimer’s disease symptoms and pathology,” he said. “That’s something that needs longer follow-up.”
Important differentiation
Commenting on the research, Rebecca Edelmayer, PhD, senior director of scientific engagement, Alzheimer’s Association, said the study provides important information. The inclusion of plasma biomarkers in this research is “really critical to tease out what’s the impact of COVID itself on the brain,” said Dr. Edelmayer.
“We’re in an era of biomarkers when it comes to Alzheimer’s disease and other dementias, and being able to define those changes that are happening in the brain over time is going to be really critical and aid in early detection and accurate diagnoses,” she said.
What is still to be learned is what these biomarkers reveal long term, said Dr. Edelmayer. “Do those biological markers change? Do they go back to normal? A lot of that is still unknown,” she said.
She noted that many diseases that are linked to inflammation produce similar biomarkers in the brain – for example, neurofilament light.
With other viral infections, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), similar associations between the infection and cognition have been reported, said Dr. Edelmayer.
“But there are still a lot of questions around cause and effect. Is it really a direct effect of the virus on the brain itself? Is it an effect of having an enormous amount of inflammation going on in the body? A lot of that still needs to be teased out,” she commented.
The study was supported by the National Institutes of Health, the Alzheimer’s Association, and the State of New York. Dr. Wisniewski has consulted for Grifols, Amylon Pharmaceuticals, and Alzamed Neuro; 30 NYU patents are related to AD therapeutics.
A version of this article first appeared on Medscape.com.
, a new study shows.
These results suggest that COVID-19 may accelerate Alzheimer’s disease symptoms and pathology, said study investigator Thomas Wisniewski, MD, professor of neurology, pathology, and psychiatry at New York University.
The findings were presented here at the Alzheimer’s Association International Conference (AAIC) 2021.
Strong correlation
There’s a clear association between SARS-CoV-2 infection and Alzheimer’s disease-related dementia. Patients with Alzheimer’s disease are at threefold higher risk for the infection and have a twofold higher risk for death, Dr. Wisniewski told meeting delegates.
He and his colleagues conducted a prospective study of patients who had tested positive for SARS-CoV-2 and who experienced neurologic sequelae and SARS-CoV-2 patients who were without neurologic sequelae. All patients were hospitalized from March 10 to May 20, 2020. This was during a period when New York City was overwhelmed by COVID: About 35% of hospitalized patients had COVID.
Of those who experienced neurologic events, the most common “by far and away” (51%) was toxic metabolic encephalopathy (TME), said Dr. Wisniewski. Other associations included seizures, hypoxic/anoxic injury, and ischemic stroke.
The most common TMEs were septic and hypoxic ischemia. In most patients (78%), TME had more than one cause.
Researchers followed 196 patients with COVID and neurologic complications (case patients) and 186 matched control patients who had no neurologic complications over a period of 6 months.
“Unfortunately, both groups had poor outcomes,” said Dr. Wisniewski. About 50% had impaired cognition, and 56% experienced limitations in activities of daily living.
However, those patients with COVID-19 who had neurologic sequelae “fared even worse,” said Dr. Wisniewski. Compared with control patients, they had twofold worse Modified Rankin Scale scores and worse scores on activity of daily living, and they were much less likely to return to work.
Mechanisms by which COVID-19 affects longer-term cognitive dysfunction are unclear, but inflammation likely plays a role.
The research team compared a number of Alzheimer’s disease plasma biomarkers in 158 patients with COVID-19 who had neurologic symptoms and 152 COVID patients with COVID but no neurologic symptoms. They found marked elevations of neurofilament light, a marker of neuronal injury, in those with symptoms (P = .0003) as well as increased glial fibrillary acid protein, a marker of neuroinflammation (P = .0098).
Ubiquitin carboxyl-terminal hydrolase L1, another marker of neuronal injury, was also elevated in those with neurologic symptoms. Regarding Alzheimer’s disease pathology, total tau (t-tau) and phosphorylated tau “also tracked with neurological sequelae,” said Dr. Wisniewski.
There was no difference in levels of amyloid beta 40 (A beta 40) between groups. However, A beta 42 plasma levels were significantly lower in those with neurologic effects, suggesting higher levels in the brain. In addition, the ratio of t-tau to A beta 42 “clearly differentiated the two groups,” he said.
“Serum biomarkers of neuroinflammation and neuronal injury and Alzheimer’s disease correlate strongly, perhaps suggesting that folks with COVID infection and neurological sequelae may have an acceleration of Alzheimer’s disease symptoms and pathology,” he said. “That’s something that needs longer follow-up.”
Important differentiation
Commenting on the research, Rebecca Edelmayer, PhD, senior director of scientific engagement, Alzheimer’s Association, said the study provides important information. The inclusion of plasma biomarkers in this research is “really critical to tease out what’s the impact of COVID itself on the brain,” said Dr. Edelmayer.
“We’re in an era of biomarkers when it comes to Alzheimer’s disease and other dementias, and being able to define those changes that are happening in the brain over time is going to be really critical and aid in early detection and accurate diagnoses,” she said.
What is still to be learned is what these biomarkers reveal long term, said Dr. Edelmayer. “Do those biological markers change? Do they go back to normal? A lot of that is still unknown,” she said.
She noted that many diseases that are linked to inflammation produce similar biomarkers in the brain – for example, neurofilament light.
With other viral infections, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), similar associations between the infection and cognition have been reported, said Dr. Edelmayer.
“But there are still a lot of questions around cause and effect. Is it really a direct effect of the virus on the brain itself? Is it an effect of having an enormous amount of inflammation going on in the body? A lot of that still needs to be teased out,” she commented.
The study was supported by the National Institutes of Health, the Alzheimer’s Association, and the State of New York. Dr. Wisniewski has consulted for Grifols, Amylon Pharmaceuticals, and Alzamed Neuro; 30 NYU patents are related to AD therapeutics.
A version of this article first appeared on Medscape.com.
, a new study shows.
These results suggest that COVID-19 may accelerate Alzheimer’s disease symptoms and pathology, said study investigator Thomas Wisniewski, MD, professor of neurology, pathology, and psychiatry at New York University.
The findings were presented here at the Alzheimer’s Association International Conference (AAIC) 2021.
Strong correlation
There’s a clear association between SARS-CoV-2 infection and Alzheimer’s disease-related dementia. Patients with Alzheimer’s disease are at threefold higher risk for the infection and have a twofold higher risk for death, Dr. Wisniewski told meeting delegates.
He and his colleagues conducted a prospective study of patients who had tested positive for SARS-CoV-2 and who experienced neurologic sequelae and SARS-CoV-2 patients who were without neurologic sequelae. All patients were hospitalized from March 10 to May 20, 2020. This was during a period when New York City was overwhelmed by COVID: About 35% of hospitalized patients had COVID.
Of those who experienced neurologic events, the most common “by far and away” (51%) was toxic metabolic encephalopathy (TME), said Dr. Wisniewski. Other associations included seizures, hypoxic/anoxic injury, and ischemic stroke.
The most common TMEs were septic and hypoxic ischemia. In most patients (78%), TME had more than one cause.
Researchers followed 196 patients with COVID and neurologic complications (case patients) and 186 matched control patients who had no neurologic complications over a period of 6 months.
“Unfortunately, both groups had poor outcomes,” said Dr. Wisniewski. About 50% had impaired cognition, and 56% experienced limitations in activities of daily living.
However, those patients with COVID-19 who had neurologic sequelae “fared even worse,” said Dr. Wisniewski. Compared with control patients, they had twofold worse Modified Rankin Scale scores and worse scores on activity of daily living, and they were much less likely to return to work.
Mechanisms by which COVID-19 affects longer-term cognitive dysfunction are unclear, but inflammation likely plays a role.
The research team compared a number of Alzheimer’s disease plasma biomarkers in 158 patients with COVID-19 who had neurologic symptoms and 152 COVID patients with COVID but no neurologic symptoms. They found marked elevations of neurofilament light, a marker of neuronal injury, in those with symptoms (P = .0003) as well as increased glial fibrillary acid protein, a marker of neuroinflammation (P = .0098).
Ubiquitin carboxyl-terminal hydrolase L1, another marker of neuronal injury, was also elevated in those with neurologic symptoms. Regarding Alzheimer’s disease pathology, total tau (t-tau) and phosphorylated tau “also tracked with neurological sequelae,” said Dr. Wisniewski.
There was no difference in levels of amyloid beta 40 (A beta 40) between groups. However, A beta 42 plasma levels were significantly lower in those with neurologic effects, suggesting higher levels in the brain. In addition, the ratio of t-tau to A beta 42 “clearly differentiated the two groups,” he said.
“Serum biomarkers of neuroinflammation and neuronal injury and Alzheimer’s disease correlate strongly, perhaps suggesting that folks with COVID infection and neurological sequelae may have an acceleration of Alzheimer’s disease symptoms and pathology,” he said. “That’s something that needs longer follow-up.”
Important differentiation
Commenting on the research, Rebecca Edelmayer, PhD, senior director of scientific engagement, Alzheimer’s Association, said the study provides important information. The inclusion of plasma biomarkers in this research is “really critical to tease out what’s the impact of COVID itself on the brain,” said Dr. Edelmayer.
“We’re in an era of biomarkers when it comes to Alzheimer’s disease and other dementias, and being able to define those changes that are happening in the brain over time is going to be really critical and aid in early detection and accurate diagnoses,” she said.
What is still to be learned is what these biomarkers reveal long term, said Dr. Edelmayer. “Do those biological markers change? Do they go back to normal? A lot of that is still unknown,” she said.
She noted that many diseases that are linked to inflammation produce similar biomarkers in the brain – for example, neurofilament light.
With other viral infections, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), similar associations between the infection and cognition have been reported, said Dr. Edelmayer.
“But there are still a lot of questions around cause and effect. Is it really a direct effect of the virus on the brain itself? Is it an effect of having an enormous amount of inflammation going on in the body? A lot of that still needs to be teased out,” she commented.
The study was supported by the National Institutes of Health, the Alzheimer’s Association, and the State of New York. Dr. Wisniewski has consulted for Grifols, Amylon Pharmaceuticals, and Alzamed Neuro; 30 NYU patents are related to AD therapeutics.
A version of this article first appeared on Medscape.com.
From AAIC 2021
Can a supplement that mimics the keto diet reduce seizures?
early research suggests. However, at least one expert has concerns.
In an open-label feasibility study, researchers assessed a liquid supplement known as K.Vita (Vitaflo International), which contains both decanoic acid and octanoic acid.
Although the study was small, the findings are promising, said coinvestigator Matthew Walker, MD, PhD, University College London Institute of Neurology, department of clinical and experimental epilepsy.
“The dietary supplement was reasonably well tolerated and while we weren’t specifically looking for efficacy here, we did see some patients had quite dramatic results in terms of reduced seizures,” Dr. Walker said.
Unlike the ketogenic diet, this dietary supplement is “very easy” to follow, involves only minor dietary modifications, and doesn’t require the intervention of a dietitian, he added.
The findings were published online July 23, 2021, in Brain Communications.
Key ingredients
In the ketogenic diet, the body uses body fat as its primary fuel source. The switch from carbohydrates to fat for body fuel results in built-up ketones.
Previous research shows the ketogenic diet is effective in reducing seizures in some patients with epilepsy. However, many patients find it difficult to tolerate, especially for extended periods. Dr. Walker also noted that ketones may have other long-term side effects, including osteoporosis.
He added that his team was keen to learn what elements of the ketogenic diet affect seizures. “Interestingly, we found that one of the fats used in the ketogenic diet, decanoic acid, has quite marked antiseizure effects,” Dr. Walker said.
Previous research has shown that decanoic acid, a medium-chain triglyceride–derived fatty acid, can cross the blood-brain barrier and decrease excitatory neurotransmission and network excitability in vitro.
Dr. Walker noted that ketones are necessary in order to reduce seizures.
“Rather than have a very high-fat, low-carbohydrate diet that causes ketones, we thought ‘why don’t we use a diet in which we just use mainly this fat, this decanoic acid, and avoid ketosis,’ ” he said.
The researchers then went to work developing the K.Vita dietary supplement, which mainly contains decanoic acid but also another fat, octanoic acid.
Assessing feasibility
The feasibility study included 61 patients (59% female) who began taking the supplement. Of these, 35 were children (aged 3-18 years) and 26 were adults. The children had Dravet syndrome or another genetically driven form of epilepsy, while most of the adults had a focal epilepsy.
All participants had failed multiple antiseizure medications – a median of 3 for children and 10 for adults who completed the trial. Of the 61 original participants, 20 (19 children and 1 adult) had tried the ketogenic diet but had stopped it for various reasons, including noncompliance and lack of efficacy.
The liquid supplement was introduced gradually. The amount administered was based on weight in the children and was a standard amount in adults, with the target being 240 mL.
Participants consumed the supplement in equal servings taken at regular intervals as part of a meal or snack. They could take it alone or mix it with yogurt or another food.
Patients with feeding tubes took the supplement immediately before or after or mixed into an enteral feed, with a water flush afterward.
Researchers provided patients and caregivers with guidance on excluding highly refined sugary foods and beverages. Starchy foods such as bread, pasta, rice, and potatoes were not restricted.
The study consisted of three visits: baseline, 5 weeks, and 12 weeks, in addition to regular phone and email contact. Participants were also asked to keep a seizure diary.
Highly acceptable to patients
Overall, the study withdrawal rate was 33%. After a protocol change involving a slower introduction of the supplement, there were fewer withdrawals, Dr. Walker reported. He noted that the proportion of participants who completed the study (41 of 61) is “much better than with most studies of adults following the ketogenic diet.”
The most frequently reported gastrointestinal symptoms with the supplement were bloating and constipation, but these were predominantly mild and tended to decrease over time. This, said Dr. Walker, contrasts to the ketogenic diet where side effects tend to persist.
There was no significant change in body weight or body mass index. “We did not see weight gain as a problem at all,” Dr. Walker said.
Of 15 caregivers and 19 adults who returned an acceptability questionnaire, 84% agreed or strongly agreed the supplement had a good flavor (strawberry); 88% liked the appearance and color; 77% liked the texture and consistency; and 88% agreed or strongly agreed it was easy to take.
About one-third of adults and two-thirds of caregivers said they believed the supplement reduced seizures.
50% seizure reduction
Only three children and one adult became ketotic. This is typically classified as a beta-hydroxybutyrate (BHB) greater than 1 mmol/L (10.4 mg/dL). The BHB levels detected were markedly lower than those observed in individuals following a ketogenic diet, the investigators note.
Of the 41 participants, 19 completed the diaries. There were also data from physician recordings, so researchers were able to retrieve seizure frequencies for 32 of the 41 (78%). Of these 32 patients, 14 (44%) had a 50% or greater reduction in seizures. Overall, children and adults “responded similarly,” Dr. Walker said.
He acknowledged the study numbers are small and emphasized that larger studies are needed to determine efficacy. He also hopes for a future randomized controlled trial comparing K.Vita with another supplement that contains different types of fats.
Interestingly, the product has already “passed” the regulatory approval process in the United Kingdom, so it can be labeled as a medicinal food and should be available for use at the beginning of 2022, Dr. Walker said.
Study concerns
Asked to comment on the findings, Daniel Goldenholz, MD, PhD, instructor in the department of neurology, Beth Israel Deaconess Medical Center, Boston, said the supplement may be helpful, but he has concerns about the study.
Many patients with epilepsy are “desperate” for therapies that will help treat their seizures, said Dr. Goldenholz, who was not involved with the research. “If there’s a dietary therapy that has the potential for being helpful, I’m loving that. I need that. My patients are begging for something that works.” It is “really exciting” that researchers are working on that goal, Dr. Goldenholz added.
However, he noted that it is too soon to start talking to patients about this new product. He also pointed out that a significant fraction of the study participants dropped out, many because they couldn’t tolerate the supplement. In addition, others didn’t produce a seizure diary.
Dr. Goldenholz and colleagues have published several studies showing that patients with no intervention at all can sometimes show a reduction in seizures compared with their baseline results.
“We found sizable 50% reductions attributable entirely to the natural fluctuations in seizure rates, rather than any therapy at all, he said.
Dr. Goldenholz added that he hopes to see future studies on this topic, and on similar therapies “with sufficient data and more reliable metrics for efficacy.”
The study was funded by Vitaflo International. Dr. Walker reports having received grants from Vitaflo International and personal fees from UCB Pharma, Eisai, and Sage. In addition, along with colleagues, he has a patent (Nutritional product) pending.
A version of this article first appeared on Medscape.com.
early research suggests. However, at least one expert has concerns.
In an open-label feasibility study, researchers assessed a liquid supplement known as K.Vita (Vitaflo International), which contains both decanoic acid and octanoic acid.
Although the study was small, the findings are promising, said coinvestigator Matthew Walker, MD, PhD, University College London Institute of Neurology, department of clinical and experimental epilepsy.
“The dietary supplement was reasonably well tolerated and while we weren’t specifically looking for efficacy here, we did see some patients had quite dramatic results in terms of reduced seizures,” Dr. Walker said.
Unlike the ketogenic diet, this dietary supplement is “very easy” to follow, involves only minor dietary modifications, and doesn’t require the intervention of a dietitian, he added.
The findings were published online July 23, 2021, in Brain Communications.
Key ingredients
In the ketogenic diet, the body uses body fat as its primary fuel source. The switch from carbohydrates to fat for body fuel results in built-up ketones.
Previous research shows the ketogenic diet is effective in reducing seizures in some patients with epilepsy. However, many patients find it difficult to tolerate, especially for extended periods. Dr. Walker also noted that ketones may have other long-term side effects, including osteoporosis.
He added that his team was keen to learn what elements of the ketogenic diet affect seizures. “Interestingly, we found that one of the fats used in the ketogenic diet, decanoic acid, has quite marked antiseizure effects,” Dr. Walker said.
Previous research has shown that decanoic acid, a medium-chain triglyceride–derived fatty acid, can cross the blood-brain barrier and decrease excitatory neurotransmission and network excitability in vitro.
Dr. Walker noted that ketones are necessary in order to reduce seizures.
“Rather than have a very high-fat, low-carbohydrate diet that causes ketones, we thought ‘why don’t we use a diet in which we just use mainly this fat, this decanoic acid, and avoid ketosis,’ ” he said.
The researchers then went to work developing the K.Vita dietary supplement, which mainly contains decanoic acid but also another fat, octanoic acid.
Assessing feasibility
The feasibility study included 61 patients (59% female) who began taking the supplement. Of these, 35 were children (aged 3-18 years) and 26 were adults. The children had Dravet syndrome or another genetically driven form of epilepsy, while most of the adults had a focal epilepsy.
All participants had failed multiple antiseizure medications – a median of 3 for children and 10 for adults who completed the trial. Of the 61 original participants, 20 (19 children and 1 adult) had tried the ketogenic diet but had stopped it for various reasons, including noncompliance and lack of efficacy.
The liquid supplement was introduced gradually. The amount administered was based on weight in the children and was a standard amount in adults, with the target being 240 mL.
Participants consumed the supplement in equal servings taken at regular intervals as part of a meal or snack. They could take it alone or mix it with yogurt or another food.
Patients with feeding tubes took the supplement immediately before or after or mixed into an enteral feed, with a water flush afterward.
Researchers provided patients and caregivers with guidance on excluding highly refined sugary foods and beverages. Starchy foods such as bread, pasta, rice, and potatoes were not restricted.
The study consisted of three visits: baseline, 5 weeks, and 12 weeks, in addition to regular phone and email contact. Participants were also asked to keep a seizure diary.
Highly acceptable to patients
Overall, the study withdrawal rate was 33%. After a protocol change involving a slower introduction of the supplement, there were fewer withdrawals, Dr. Walker reported. He noted that the proportion of participants who completed the study (41 of 61) is “much better than with most studies of adults following the ketogenic diet.”
The most frequently reported gastrointestinal symptoms with the supplement were bloating and constipation, but these were predominantly mild and tended to decrease over time. This, said Dr. Walker, contrasts to the ketogenic diet where side effects tend to persist.
There was no significant change in body weight or body mass index. “We did not see weight gain as a problem at all,” Dr. Walker said.
Of 15 caregivers and 19 adults who returned an acceptability questionnaire, 84% agreed or strongly agreed the supplement had a good flavor (strawberry); 88% liked the appearance and color; 77% liked the texture and consistency; and 88% agreed or strongly agreed it was easy to take.
About one-third of adults and two-thirds of caregivers said they believed the supplement reduced seizures.
50% seizure reduction
Only three children and one adult became ketotic. This is typically classified as a beta-hydroxybutyrate (BHB) greater than 1 mmol/L (10.4 mg/dL). The BHB levels detected were markedly lower than those observed in individuals following a ketogenic diet, the investigators note.
Of the 41 participants, 19 completed the diaries. There were also data from physician recordings, so researchers were able to retrieve seizure frequencies for 32 of the 41 (78%). Of these 32 patients, 14 (44%) had a 50% or greater reduction in seizures. Overall, children and adults “responded similarly,” Dr. Walker said.
He acknowledged the study numbers are small and emphasized that larger studies are needed to determine efficacy. He also hopes for a future randomized controlled trial comparing K.Vita with another supplement that contains different types of fats.
Interestingly, the product has already “passed” the regulatory approval process in the United Kingdom, so it can be labeled as a medicinal food and should be available for use at the beginning of 2022, Dr. Walker said.
Study concerns
Asked to comment on the findings, Daniel Goldenholz, MD, PhD, instructor in the department of neurology, Beth Israel Deaconess Medical Center, Boston, said the supplement may be helpful, but he has concerns about the study.
Many patients with epilepsy are “desperate” for therapies that will help treat their seizures, said Dr. Goldenholz, who was not involved with the research. “If there’s a dietary therapy that has the potential for being helpful, I’m loving that. I need that. My patients are begging for something that works.” It is “really exciting” that researchers are working on that goal, Dr. Goldenholz added.
However, he noted that it is too soon to start talking to patients about this new product. He also pointed out that a significant fraction of the study participants dropped out, many because they couldn’t tolerate the supplement. In addition, others didn’t produce a seizure diary.
Dr. Goldenholz and colleagues have published several studies showing that patients with no intervention at all can sometimes show a reduction in seizures compared with their baseline results.
“We found sizable 50% reductions attributable entirely to the natural fluctuations in seizure rates, rather than any therapy at all, he said.
Dr. Goldenholz added that he hopes to see future studies on this topic, and on similar therapies “with sufficient data and more reliable metrics for efficacy.”
The study was funded by Vitaflo International. Dr. Walker reports having received grants from Vitaflo International and personal fees from UCB Pharma, Eisai, and Sage. In addition, along with colleagues, he has a patent (Nutritional product) pending.
A version of this article first appeared on Medscape.com.
early research suggests. However, at least one expert has concerns.
In an open-label feasibility study, researchers assessed a liquid supplement known as K.Vita (Vitaflo International), which contains both decanoic acid and octanoic acid.
Although the study was small, the findings are promising, said coinvestigator Matthew Walker, MD, PhD, University College London Institute of Neurology, department of clinical and experimental epilepsy.
“The dietary supplement was reasonably well tolerated and while we weren’t specifically looking for efficacy here, we did see some patients had quite dramatic results in terms of reduced seizures,” Dr. Walker said.
Unlike the ketogenic diet, this dietary supplement is “very easy” to follow, involves only minor dietary modifications, and doesn’t require the intervention of a dietitian, he added.
The findings were published online July 23, 2021, in Brain Communications.
Key ingredients
In the ketogenic diet, the body uses body fat as its primary fuel source. The switch from carbohydrates to fat for body fuel results in built-up ketones.
Previous research shows the ketogenic diet is effective in reducing seizures in some patients with epilepsy. However, many patients find it difficult to tolerate, especially for extended periods. Dr. Walker also noted that ketones may have other long-term side effects, including osteoporosis.
He added that his team was keen to learn what elements of the ketogenic diet affect seizures. “Interestingly, we found that one of the fats used in the ketogenic diet, decanoic acid, has quite marked antiseizure effects,” Dr. Walker said.
Previous research has shown that decanoic acid, a medium-chain triglyceride–derived fatty acid, can cross the blood-brain barrier and decrease excitatory neurotransmission and network excitability in vitro.
Dr. Walker noted that ketones are necessary in order to reduce seizures.
“Rather than have a very high-fat, low-carbohydrate diet that causes ketones, we thought ‘why don’t we use a diet in which we just use mainly this fat, this decanoic acid, and avoid ketosis,’ ” he said.
The researchers then went to work developing the K.Vita dietary supplement, which mainly contains decanoic acid but also another fat, octanoic acid.
Assessing feasibility
The feasibility study included 61 patients (59% female) who began taking the supplement. Of these, 35 were children (aged 3-18 years) and 26 were adults. The children had Dravet syndrome or another genetically driven form of epilepsy, while most of the adults had a focal epilepsy.
All participants had failed multiple antiseizure medications – a median of 3 for children and 10 for adults who completed the trial. Of the 61 original participants, 20 (19 children and 1 adult) had tried the ketogenic diet but had stopped it for various reasons, including noncompliance and lack of efficacy.
The liquid supplement was introduced gradually. The amount administered was based on weight in the children and was a standard amount in adults, with the target being 240 mL.
Participants consumed the supplement in equal servings taken at regular intervals as part of a meal or snack. They could take it alone or mix it with yogurt or another food.
Patients with feeding tubes took the supplement immediately before or after or mixed into an enteral feed, with a water flush afterward.
Researchers provided patients and caregivers with guidance on excluding highly refined sugary foods and beverages. Starchy foods such as bread, pasta, rice, and potatoes were not restricted.
The study consisted of three visits: baseline, 5 weeks, and 12 weeks, in addition to regular phone and email contact. Participants were also asked to keep a seizure diary.
Highly acceptable to patients
Overall, the study withdrawal rate was 33%. After a protocol change involving a slower introduction of the supplement, there were fewer withdrawals, Dr. Walker reported. He noted that the proportion of participants who completed the study (41 of 61) is “much better than with most studies of adults following the ketogenic diet.”
The most frequently reported gastrointestinal symptoms with the supplement were bloating and constipation, but these were predominantly mild and tended to decrease over time. This, said Dr. Walker, contrasts to the ketogenic diet where side effects tend to persist.
There was no significant change in body weight or body mass index. “We did not see weight gain as a problem at all,” Dr. Walker said.
Of 15 caregivers and 19 adults who returned an acceptability questionnaire, 84% agreed or strongly agreed the supplement had a good flavor (strawberry); 88% liked the appearance and color; 77% liked the texture and consistency; and 88% agreed or strongly agreed it was easy to take.
About one-third of adults and two-thirds of caregivers said they believed the supplement reduced seizures.
50% seizure reduction
Only three children and one adult became ketotic. This is typically classified as a beta-hydroxybutyrate (BHB) greater than 1 mmol/L (10.4 mg/dL). The BHB levels detected were markedly lower than those observed in individuals following a ketogenic diet, the investigators note.
Of the 41 participants, 19 completed the diaries. There were also data from physician recordings, so researchers were able to retrieve seizure frequencies for 32 of the 41 (78%). Of these 32 patients, 14 (44%) had a 50% or greater reduction in seizures. Overall, children and adults “responded similarly,” Dr. Walker said.
He acknowledged the study numbers are small and emphasized that larger studies are needed to determine efficacy. He also hopes for a future randomized controlled trial comparing K.Vita with another supplement that contains different types of fats.
Interestingly, the product has already “passed” the regulatory approval process in the United Kingdom, so it can be labeled as a medicinal food and should be available for use at the beginning of 2022, Dr. Walker said.
Study concerns
Asked to comment on the findings, Daniel Goldenholz, MD, PhD, instructor in the department of neurology, Beth Israel Deaconess Medical Center, Boston, said the supplement may be helpful, but he has concerns about the study.
Many patients with epilepsy are “desperate” for therapies that will help treat their seizures, said Dr. Goldenholz, who was not involved with the research. “If there’s a dietary therapy that has the potential for being helpful, I’m loving that. I need that. My patients are begging for something that works.” It is “really exciting” that researchers are working on that goal, Dr. Goldenholz added.
However, he noted that it is too soon to start talking to patients about this new product. He also pointed out that a significant fraction of the study participants dropped out, many because they couldn’t tolerate the supplement. In addition, others didn’t produce a seizure diary.
Dr. Goldenholz and colleagues have published several studies showing that patients with no intervention at all can sometimes show a reduction in seizures compared with their baseline results.
“We found sizable 50% reductions attributable entirely to the natural fluctuations in seizure rates, rather than any therapy at all, he said.
Dr. Goldenholz added that he hopes to see future studies on this topic, and on similar therapies “with sufficient data and more reliable metrics for efficacy.”
The study was funded by Vitaflo International. Dr. Walker reports having received grants from Vitaflo International and personal fees from UCB Pharma, Eisai, and Sage. In addition, along with colleagues, he has a patent (Nutritional product) pending.
A version of this article first appeared on Medscape.com.
FROM BRAIN COMMUNICATION
Changes in metabolism tied to risk of subsequent dementia
in new findings that may provide a prevention target.
Investigators found one of the clusters includes small high-density lipoprotein (HDL) metabolites associated with vascular dementia, while another cluster involves ketone bodies and citrate that are primarily associated with Alzheimer’s disease.
Ketone bodies, or ketones, are three related compounds – acetone, acetoacetic acid, and beta-hydroxybutyric acid (BHB) – produced by the liver during fat metabolism. Citrate is a salt or ester of citric acid.
These metabolite clusters are not only linked to the future development of dementia but also correlate with early pathology in those under age 60 years, said study investigator Cornelia M. van Duijn, PhD, professor of epidemiology at Nuffield Department of Population Health, Oxford (England) University.
“These metabolites flag early and late pathology and may be relevant as targets for prevention of dementia,” she noted.
The findings were presented at the 2021 Alzheimer’s Association International Conference.
Weight loss before dementia explained?
For the study, investigators included 125,000 patients from the UK Biobank, which includes 51,031 who were over age 60 at baseline. Of these, 1,188 developed dementia during a follow-up of about 10 years; 553 were diagnosed with Alzheimer’s disease and 298 with vascular dementia.
Researchers used a platform that covers 249 metabolic measures, including small molecules, fatty acids, and lipoprotein lipids.
They estimated risk associated with these metabolites, adjusting for age, sex, body mass index, technical variables, ethnicity, smoking, alcohol, education, metabolic and neuropsychiatric medication, and APOE4 genotypes.
Of the 249 metabolites, 47 (19%) were associated with dementia risk in those over age 60, after adjustment.
The investigators examined effect estimates for associations of metabolites with both Alzheimer’s disease and vascular dementia over age 60 versus hippocampal volume under age 60. They found a “very strong, very significant” association for Alzheimer’s disease, and a “marginally significant” association for vascular dementia, said Dr. van Duijn.
This would be expected, as there is a much stronger correlation between hippocampal and Alzheimer’s disease versus vascular dementia, she added.
“We not only see that the metabolites predict dementia, but also early pathology. This makes these findings rather interesting for targeting prevention,” she said. An analysis of total brain volume showed “very strong, very similar, very significant associations” for both Alzheimer’s disease and vascular dementia,” added Dr. van Duijn.
The researchers found a major shift in various metabolites involved in energy metabolism in the 10-year period before the diagnosis of Alzheimer’s disease. These changes include low levels of branched-chain amino acids and omega-3 fatty acids and high levels of glucose, citrate, acetone, beta-hydroxybutyrate, and acetate. “This finding is in line with that in APOE models that show reduced energy metabolism over age in the brain,” said Dr. van Duijn.
She added that high levels of some of these metabolites are associated with low body weight before dementia onset, which may explain the weight loss seen in patients before developing the disease. “Our hypothesis is that the liver is burning the fat reserves of the patients in order to provide the brain with fuel,” she explained.
Diet a prevention target?
The results also showed ketone bodies increase with age, which may represent the aging brain’s “compensation mechanism” to deal with an energy shortage, said Dr. van Duijn. “Supplementation of ketone bodies, branched-chain amino and omega-3 fatty acids may help support brain function.”
The fact that ketone bodies were positively associated with the risk of dementia is “a very important finding,” she said.
Following this and other presentations, session cochair Rima Kaddurah-Daouk, PhD, professor in psychiatry and behavioral sciences, Institute for Brain Sciences, Duke University, Durham, N.C., noted the research is “an important part of trying to decipher some of the mysteries in Alzheimer’s disease.”
The research contributes to the understanding of how nutrition and diet could influence metabolism and then the brain and is “opening the horizon” for thinking about “strategies for therapeutic interventions,” she said.
The study received funding support from the National Institute on Aging. The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
in new findings that may provide a prevention target.
Investigators found one of the clusters includes small high-density lipoprotein (HDL) metabolites associated with vascular dementia, while another cluster involves ketone bodies and citrate that are primarily associated with Alzheimer’s disease.
Ketone bodies, or ketones, are three related compounds – acetone, acetoacetic acid, and beta-hydroxybutyric acid (BHB) – produced by the liver during fat metabolism. Citrate is a salt or ester of citric acid.
These metabolite clusters are not only linked to the future development of dementia but also correlate with early pathology in those under age 60 years, said study investigator Cornelia M. van Duijn, PhD, professor of epidemiology at Nuffield Department of Population Health, Oxford (England) University.
“These metabolites flag early and late pathology and may be relevant as targets for prevention of dementia,” she noted.
The findings were presented at the 2021 Alzheimer’s Association International Conference.
Weight loss before dementia explained?
For the study, investigators included 125,000 patients from the UK Biobank, which includes 51,031 who were over age 60 at baseline. Of these, 1,188 developed dementia during a follow-up of about 10 years; 553 were diagnosed with Alzheimer’s disease and 298 with vascular dementia.
Researchers used a platform that covers 249 metabolic measures, including small molecules, fatty acids, and lipoprotein lipids.
They estimated risk associated with these metabolites, adjusting for age, sex, body mass index, technical variables, ethnicity, smoking, alcohol, education, metabolic and neuropsychiatric medication, and APOE4 genotypes.
Of the 249 metabolites, 47 (19%) were associated with dementia risk in those over age 60, after adjustment.
The investigators examined effect estimates for associations of metabolites with both Alzheimer’s disease and vascular dementia over age 60 versus hippocampal volume under age 60. They found a “very strong, very significant” association for Alzheimer’s disease, and a “marginally significant” association for vascular dementia, said Dr. van Duijn.
This would be expected, as there is a much stronger correlation between hippocampal and Alzheimer’s disease versus vascular dementia, she added.
“We not only see that the metabolites predict dementia, but also early pathology. This makes these findings rather interesting for targeting prevention,” she said. An analysis of total brain volume showed “very strong, very similar, very significant associations” for both Alzheimer’s disease and vascular dementia,” added Dr. van Duijn.
The researchers found a major shift in various metabolites involved in energy metabolism in the 10-year period before the diagnosis of Alzheimer’s disease. These changes include low levels of branched-chain amino acids and omega-3 fatty acids and high levels of glucose, citrate, acetone, beta-hydroxybutyrate, and acetate. “This finding is in line with that in APOE models that show reduced energy metabolism over age in the brain,” said Dr. van Duijn.
She added that high levels of some of these metabolites are associated with low body weight before dementia onset, which may explain the weight loss seen in patients before developing the disease. “Our hypothesis is that the liver is burning the fat reserves of the patients in order to provide the brain with fuel,” she explained.
Diet a prevention target?
The results also showed ketone bodies increase with age, which may represent the aging brain’s “compensation mechanism” to deal with an energy shortage, said Dr. van Duijn. “Supplementation of ketone bodies, branched-chain amino and omega-3 fatty acids may help support brain function.”
The fact that ketone bodies were positively associated with the risk of dementia is “a very important finding,” she said.
Following this and other presentations, session cochair Rima Kaddurah-Daouk, PhD, professor in psychiatry and behavioral sciences, Institute for Brain Sciences, Duke University, Durham, N.C., noted the research is “an important part of trying to decipher some of the mysteries in Alzheimer’s disease.”
The research contributes to the understanding of how nutrition and diet could influence metabolism and then the brain and is “opening the horizon” for thinking about “strategies for therapeutic interventions,” she said.
The study received funding support from the National Institute on Aging. The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
in new findings that may provide a prevention target.
Investigators found one of the clusters includes small high-density lipoprotein (HDL) metabolites associated with vascular dementia, while another cluster involves ketone bodies and citrate that are primarily associated with Alzheimer’s disease.
Ketone bodies, or ketones, are three related compounds – acetone, acetoacetic acid, and beta-hydroxybutyric acid (BHB) – produced by the liver during fat metabolism. Citrate is a salt or ester of citric acid.
These metabolite clusters are not only linked to the future development of dementia but also correlate with early pathology in those under age 60 years, said study investigator Cornelia M. van Duijn, PhD, professor of epidemiology at Nuffield Department of Population Health, Oxford (England) University.
“These metabolites flag early and late pathology and may be relevant as targets for prevention of dementia,” she noted.
The findings were presented at the 2021 Alzheimer’s Association International Conference.
Weight loss before dementia explained?
For the study, investigators included 125,000 patients from the UK Biobank, which includes 51,031 who were over age 60 at baseline. Of these, 1,188 developed dementia during a follow-up of about 10 years; 553 were diagnosed with Alzheimer’s disease and 298 with vascular dementia.
Researchers used a platform that covers 249 metabolic measures, including small molecules, fatty acids, and lipoprotein lipids.
They estimated risk associated with these metabolites, adjusting for age, sex, body mass index, technical variables, ethnicity, smoking, alcohol, education, metabolic and neuropsychiatric medication, and APOE4 genotypes.
Of the 249 metabolites, 47 (19%) were associated with dementia risk in those over age 60, after adjustment.
The investigators examined effect estimates for associations of metabolites with both Alzheimer’s disease and vascular dementia over age 60 versus hippocampal volume under age 60. They found a “very strong, very significant” association for Alzheimer’s disease, and a “marginally significant” association for vascular dementia, said Dr. van Duijn.
This would be expected, as there is a much stronger correlation between hippocampal and Alzheimer’s disease versus vascular dementia, she added.
“We not only see that the metabolites predict dementia, but also early pathology. This makes these findings rather interesting for targeting prevention,” she said. An analysis of total brain volume showed “very strong, very similar, very significant associations” for both Alzheimer’s disease and vascular dementia,” added Dr. van Duijn.
The researchers found a major shift in various metabolites involved in energy metabolism in the 10-year period before the diagnosis of Alzheimer’s disease. These changes include low levels of branched-chain amino acids and omega-3 fatty acids and high levels of glucose, citrate, acetone, beta-hydroxybutyrate, and acetate. “This finding is in line with that in APOE models that show reduced energy metabolism over age in the brain,” said Dr. van Duijn.
She added that high levels of some of these metabolites are associated with low body weight before dementia onset, which may explain the weight loss seen in patients before developing the disease. “Our hypothesis is that the liver is burning the fat reserves of the patients in order to provide the brain with fuel,” she explained.
Diet a prevention target?
The results also showed ketone bodies increase with age, which may represent the aging brain’s “compensation mechanism” to deal with an energy shortage, said Dr. van Duijn. “Supplementation of ketone bodies, branched-chain amino and omega-3 fatty acids may help support brain function.”
The fact that ketone bodies were positively associated with the risk of dementia is “a very important finding,” she said.
Following this and other presentations, session cochair Rima Kaddurah-Daouk, PhD, professor in psychiatry and behavioral sciences, Institute for Brain Sciences, Duke University, Durham, N.C., noted the research is “an important part of trying to decipher some of the mysteries in Alzheimer’s disease.”
The research contributes to the understanding of how nutrition and diet could influence metabolism and then the brain and is “opening the horizon” for thinking about “strategies for therapeutic interventions,” she said.
The study received funding support from the National Institute on Aging. The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAIC 2021
Coffee and the brain: ‘Concerning’ new data
according to the results of a large study.
“With coffee intake, moderation is the key, and especially high levels of consumption may have adverse long-term effects on the brain,” said study investigator Elina Hypponen, PhD, professor of nutritional and genetic epidemiology and director of the Australian Center for Precision Health at the University of South Australia.
“These new data are concerning, and there is a need to conduct further carefully controlled studies to clarify the effects of coffee on the brain.”
The study was published online June 24 in Nutritional Neuroscience.
Potent stimulant
Coffee is a potent nervous system stimulant and is among the most popular nonalcoholic beverages. Some previous research suggests it benefits the brain, but the investigators noted that other research shows a negative or U-shaped relationship.
To investigate, the researchers examined data from the U.K. Biobank, a long-term prospective epidemiologic study of more than 500,000 participants aged 37-73 years who were recruited in 22 assessment centers in the United Kingdom between March 2006 and October 2010.
During the baseline assessment, information was gathered using touchscreen questionnaires, verbal interviews, and physical examinations that involved collection of blood, urine, and saliva samples. An imaging substudy was incorporated in 2014, the goal of which was to conduct brain, heart, and body MRI imaging for 100,000 participants.
The investigators conducted analyses on disease outcomes for 398,646 participants for whom information on habitual coffee consumption was available. Brain volume analyses were conducted in 17,702 participants for whom valid brain imaging data were available.
Participants reported coffee intake in cups per day. Researchers grouped coffee consumption into seven categories: nondrinkers, decaffeinated coffee drinkers, and caffeinated coffee drinkers who consumed less than 1 cup/d, 1-2 cups/d, 3-4 cups/d, 5-6 cups/d, and more than 6 cups/d.
The reference category was those who consumed 1-2 cups/d, rather than those who abstained from coffee, because persons who abstain are more likely to be at suboptimal health.
“Comparing the health of coffee drinkers to the health of those choosing to abstain from coffee will typically lead to an impression of a health benefit, even if there would not be one,” said Dr. Hypponen.
The researchers obtained total and regional brain volumes from the MRI imaging substudy starting 4-6 years after baseline assessment. They accessed information on incident dementia and stroke using primary care data, hospital admission electronic health records, national death registers, and self-reported medical conditions.
Covariates included socioeconomic, health, and other factors, such as smoking, alcohol and tea consumption, physical activity, stressful life events, and body mass index.
The investigators found that there was a linear inverse association between coffee consumption and total brain volume (fully adjusted beta per cup, –1.42; 95% confidence interval, –1.89 to –0.94), with consistent patterns for gray matter, white matter, and hippocampal volumes.
There was no evidence to support an association with white matter hyperintensity (WMH) volume (beta –0.01; 95% CI, –0.07 to 0.05).
Higher consumption, higher risk
The analysis also revealed a nonlinear association between coffee consumption and the odds of dementia (P nonlinearity = .0001), with slightly higher odds seen with non–coffee drinkers and decaffeinated-coffee drinkers and more notable increases for participants in the highest categories of coffee consumption compared with light coffee drinkers.
After adjustment for all covariates, the odds ratio of dementia among persons in the category of coffee intake was 1.53 (95% CI, 1.28-1.83). After full adjustments, the association with heavy coffee consumption and stroke was not significant, although “we can’t exclude a weak effect,” said Dr. Hypponen.
“For the highest coffee consumption group, the data support an association which may be anywhere from 0% to 37% higher odds of stroke after full adjustment,” she added.
People at risk for hypertension may develop “unpleasant sensations” and stop drinking coffee before a serious adverse event occurs, said Dr. Hypponen. In a previous study, she and her colleagues showed that those who have genetically higher blood pressure tend to drink less coffee than their counterparts without the condition.
“This type of effect might be expected to naturally limit the adverse effects of coffee on the risk of stroke,” said Dr. Hypponen.
The odds remained elevated for participants drinking more than 6 cups/d after the researchers accounted for sleep quality. There were no differences in risk between men and women or by age.
An examination of the consumption of tea, which often contains caffeine, did not show an association with brain volume or the odds of dementia or stroke.
“We don’t know whether the difference between associations seen for coffee and tea intake reflects the difference in related caffeine intake or some other explanation, such as dehydration or effects operating through blood cholesterol,” said Dr. Hypponen.
Although reverse causation is possible, there’s no reason to believe that it is relevant to the study results. Genetic evidence suggests a causal role of higher coffee intake on risk for Alzheimer’s disease. In addition, results of a clinical trial support the association between higher caffeine intake and smaller gray matter volume, said Dr. Hypponen.
The mechanisms linking coffee consumption to brain volumes and dementia are not well established. However, Dr. Hypponen noted that caffeine has been used to induce apoptosis in cancer studies using glial cells.
“Furthermore, adenosine receptors, which mediate many of the effects of caffeine in the brain, have been suggested to influence the release of growth factors, which in turn can have an influence on astrocyte proliferation and angiogenesis in the brain,” she said.
Some types of coffee contain cafestol, which increases blood cholesterol and can have adverse effects though related mechanisms, said Dr. Hypponen.
The mechanism may also involve dehydration, which may have a harmful effect on the brain. The study suggested a correlation between dehydration and high coffee intake. “Of course, if this is the case, it is good news, as then we can do something about it simply by drinking some water every time we have a cup of coffee,” she said.
Misleading conclusions
Coffee contains antioxidants, and although previous studies have suggested it might be beneficial, this hypothesis is “too simplistic,” said Dr. Hypponen. “While coffee is not going to be all ‘bad’ either, there are a lot of controversies and suggestions about beneficial effects of coffee which may not be true, or at least do not reflect the full story.”
If the drinking of coffee is at least partly determined by an individual’s health status, then that would often lead to misleading conclusions in observational studies, said Dr. Hypponen.
“When one uses as a comparison people who already have poor health and who do not drink coffee because of that, coffee intake will by default appear beneficial simply because there are more people with disease among those choosing abstinence,” she said.
Before now, there was “very little evidence about the association between coffee intake and brain morphology,” and the studies that were conducted were relatively small, said Dr. Hypponen.
One of these smaller studies included a group of women aged 13-30 years. It found that coffee consumption was not associated with total brain volumes, but the findings suggested a U-shaped association with hippocampal volume; higher values were seen both for nondrinkers and the groups with higher consumption.
A small study of elderly patients with diabetes showed no evidence of an association with white matter volume, but there was a possible age-dependent association with gray matter volume.
The largest of the earlier studies had results that were very similar to those of the current study, suggesting that increasing coffee intake is associated with smaller hippocampal volumes, said Dr. Hypponen.
One of the study’s limitations included the fact that full dietary information was available only for a subsample and that factors such as dehydration were measured at baseline rather than at the time of brain MRI.
Another possible study limitation was the use of self-reported data and the fact that lifestyle changes may have occurred between baseline and MRI or covariate measurement.
In addition, the study is subject to a healthy-volunteer bias, and its implications are restricted to White British persons. The association needs to be studied in other ethnic populations, the authors noted.
A reason to cut back?
Commenting on the findings, Walter Willett, MD, DrPH, professor of epidemiology and nutrition, Harvard T. H. Chan School of Public Health, Boston, said the study is large and quite well done.
“It does raise questions about an increase in risk of dementia with six or more cups of coffee per day,” said Dr. Willett. “At the same time, it provides reassurance about lack of adverse effects of coffee for those consuming three or four cups per day, and little increase in risk, if any, with five cups per day.”
It’s not entirely clear whether the increase in risk with six or more cups of coffee per day represents a “true effect” of coffee, inasmuch as the study did not seem to adjust fully for dietary factors, high consumption of alcohol, or past smoking, said Dr. Willett.
The findings don’t suggest that coffee lovers should give up their Java. “But six or more cups per day is a lot, and those who drink that much might consider cutting back a bit while research continues,” said Dr. Willett.
The study was supported by the National Health and Medical Research Council.
A version of this article first appeared on Medscape.com.
according to the results of a large study.
“With coffee intake, moderation is the key, and especially high levels of consumption may have adverse long-term effects on the brain,” said study investigator Elina Hypponen, PhD, professor of nutritional and genetic epidemiology and director of the Australian Center for Precision Health at the University of South Australia.
“These new data are concerning, and there is a need to conduct further carefully controlled studies to clarify the effects of coffee on the brain.”
The study was published online June 24 in Nutritional Neuroscience.
Potent stimulant
Coffee is a potent nervous system stimulant and is among the most popular nonalcoholic beverages. Some previous research suggests it benefits the brain, but the investigators noted that other research shows a negative or U-shaped relationship.
To investigate, the researchers examined data from the U.K. Biobank, a long-term prospective epidemiologic study of more than 500,000 participants aged 37-73 years who were recruited in 22 assessment centers in the United Kingdom between March 2006 and October 2010.
During the baseline assessment, information was gathered using touchscreen questionnaires, verbal interviews, and physical examinations that involved collection of blood, urine, and saliva samples. An imaging substudy was incorporated in 2014, the goal of which was to conduct brain, heart, and body MRI imaging for 100,000 participants.
The investigators conducted analyses on disease outcomes for 398,646 participants for whom information on habitual coffee consumption was available. Brain volume analyses were conducted in 17,702 participants for whom valid brain imaging data were available.
Participants reported coffee intake in cups per day. Researchers grouped coffee consumption into seven categories: nondrinkers, decaffeinated coffee drinkers, and caffeinated coffee drinkers who consumed less than 1 cup/d, 1-2 cups/d, 3-4 cups/d, 5-6 cups/d, and more than 6 cups/d.
The reference category was those who consumed 1-2 cups/d, rather than those who abstained from coffee, because persons who abstain are more likely to be at suboptimal health.
“Comparing the health of coffee drinkers to the health of those choosing to abstain from coffee will typically lead to an impression of a health benefit, even if there would not be one,” said Dr. Hypponen.
The researchers obtained total and regional brain volumes from the MRI imaging substudy starting 4-6 years after baseline assessment. They accessed information on incident dementia and stroke using primary care data, hospital admission electronic health records, national death registers, and self-reported medical conditions.
Covariates included socioeconomic, health, and other factors, such as smoking, alcohol and tea consumption, physical activity, stressful life events, and body mass index.
The investigators found that there was a linear inverse association between coffee consumption and total brain volume (fully adjusted beta per cup, –1.42; 95% confidence interval, –1.89 to –0.94), with consistent patterns for gray matter, white matter, and hippocampal volumes.
There was no evidence to support an association with white matter hyperintensity (WMH) volume (beta –0.01; 95% CI, –0.07 to 0.05).
Higher consumption, higher risk
The analysis also revealed a nonlinear association between coffee consumption and the odds of dementia (P nonlinearity = .0001), with slightly higher odds seen with non–coffee drinkers and decaffeinated-coffee drinkers and more notable increases for participants in the highest categories of coffee consumption compared with light coffee drinkers.
After adjustment for all covariates, the odds ratio of dementia among persons in the category of coffee intake was 1.53 (95% CI, 1.28-1.83). After full adjustments, the association with heavy coffee consumption and stroke was not significant, although “we can’t exclude a weak effect,” said Dr. Hypponen.
“For the highest coffee consumption group, the data support an association which may be anywhere from 0% to 37% higher odds of stroke after full adjustment,” she added.
People at risk for hypertension may develop “unpleasant sensations” and stop drinking coffee before a serious adverse event occurs, said Dr. Hypponen. In a previous study, she and her colleagues showed that those who have genetically higher blood pressure tend to drink less coffee than their counterparts without the condition.
“This type of effect might be expected to naturally limit the adverse effects of coffee on the risk of stroke,” said Dr. Hypponen.
The odds remained elevated for participants drinking more than 6 cups/d after the researchers accounted for sleep quality. There were no differences in risk between men and women or by age.
An examination of the consumption of tea, which often contains caffeine, did not show an association with brain volume or the odds of dementia or stroke.
“We don’t know whether the difference between associations seen for coffee and tea intake reflects the difference in related caffeine intake or some other explanation, such as dehydration or effects operating through blood cholesterol,” said Dr. Hypponen.
Although reverse causation is possible, there’s no reason to believe that it is relevant to the study results. Genetic evidence suggests a causal role of higher coffee intake on risk for Alzheimer’s disease. In addition, results of a clinical trial support the association between higher caffeine intake and smaller gray matter volume, said Dr. Hypponen.
The mechanisms linking coffee consumption to brain volumes and dementia are not well established. However, Dr. Hypponen noted that caffeine has been used to induce apoptosis in cancer studies using glial cells.
“Furthermore, adenosine receptors, which mediate many of the effects of caffeine in the brain, have been suggested to influence the release of growth factors, which in turn can have an influence on astrocyte proliferation and angiogenesis in the brain,” she said.
Some types of coffee contain cafestol, which increases blood cholesterol and can have adverse effects though related mechanisms, said Dr. Hypponen.
The mechanism may also involve dehydration, which may have a harmful effect on the brain. The study suggested a correlation between dehydration and high coffee intake. “Of course, if this is the case, it is good news, as then we can do something about it simply by drinking some water every time we have a cup of coffee,” she said.
Misleading conclusions
Coffee contains antioxidants, and although previous studies have suggested it might be beneficial, this hypothesis is “too simplistic,” said Dr. Hypponen. “While coffee is not going to be all ‘bad’ either, there are a lot of controversies and suggestions about beneficial effects of coffee which may not be true, or at least do not reflect the full story.”
If the drinking of coffee is at least partly determined by an individual’s health status, then that would often lead to misleading conclusions in observational studies, said Dr. Hypponen.
“When one uses as a comparison people who already have poor health and who do not drink coffee because of that, coffee intake will by default appear beneficial simply because there are more people with disease among those choosing abstinence,” she said.
Before now, there was “very little evidence about the association between coffee intake and brain morphology,” and the studies that were conducted were relatively small, said Dr. Hypponen.
One of these smaller studies included a group of women aged 13-30 years. It found that coffee consumption was not associated with total brain volumes, but the findings suggested a U-shaped association with hippocampal volume; higher values were seen both for nondrinkers and the groups with higher consumption.
A small study of elderly patients with diabetes showed no evidence of an association with white matter volume, but there was a possible age-dependent association with gray matter volume.
The largest of the earlier studies had results that were very similar to those of the current study, suggesting that increasing coffee intake is associated with smaller hippocampal volumes, said Dr. Hypponen.
One of the study’s limitations included the fact that full dietary information was available only for a subsample and that factors such as dehydration were measured at baseline rather than at the time of brain MRI.
Another possible study limitation was the use of self-reported data and the fact that lifestyle changes may have occurred between baseline and MRI or covariate measurement.
In addition, the study is subject to a healthy-volunteer bias, and its implications are restricted to White British persons. The association needs to be studied in other ethnic populations, the authors noted.
A reason to cut back?
Commenting on the findings, Walter Willett, MD, DrPH, professor of epidemiology and nutrition, Harvard T. H. Chan School of Public Health, Boston, said the study is large and quite well done.
“It does raise questions about an increase in risk of dementia with six or more cups of coffee per day,” said Dr. Willett. “At the same time, it provides reassurance about lack of adverse effects of coffee for those consuming three or four cups per day, and little increase in risk, if any, with five cups per day.”
It’s not entirely clear whether the increase in risk with six or more cups of coffee per day represents a “true effect” of coffee, inasmuch as the study did not seem to adjust fully for dietary factors, high consumption of alcohol, or past smoking, said Dr. Willett.
The findings don’t suggest that coffee lovers should give up their Java. “But six or more cups per day is a lot, and those who drink that much might consider cutting back a bit while research continues,” said Dr. Willett.
The study was supported by the National Health and Medical Research Council.
A version of this article first appeared on Medscape.com.
according to the results of a large study.
“With coffee intake, moderation is the key, and especially high levels of consumption may have adverse long-term effects on the brain,” said study investigator Elina Hypponen, PhD, professor of nutritional and genetic epidemiology and director of the Australian Center for Precision Health at the University of South Australia.
“These new data are concerning, and there is a need to conduct further carefully controlled studies to clarify the effects of coffee on the brain.”
The study was published online June 24 in Nutritional Neuroscience.
Potent stimulant
Coffee is a potent nervous system stimulant and is among the most popular nonalcoholic beverages. Some previous research suggests it benefits the brain, but the investigators noted that other research shows a negative or U-shaped relationship.
To investigate, the researchers examined data from the U.K. Biobank, a long-term prospective epidemiologic study of more than 500,000 participants aged 37-73 years who were recruited in 22 assessment centers in the United Kingdom between March 2006 and October 2010.
During the baseline assessment, information was gathered using touchscreen questionnaires, verbal interviews, and physical examinations that involved collection of blood, urine, and saliva samples. An imaging substudy was incorporated in 2014, the goal of which was to conduct brain, heart, and body MRI imaging for 100,000 participants.
The investigators conducted analyses on disease outcomes for 398,646 participants for whom information on habitual coffee consumption was available. Brain volume analyses were conducted in 17,702 participants for whom valid brain imaging data were available.
Participants reported coffee intake in cups per day. Researchers grouped coffee consumption into seven categories: nondrinkers, decaffeinated coffee drinkers, and caffeinated coffee drinkers who consumed less than 1 cup/d, 1-2 cups/d, 3-4 cups/d, 5-6 cups/d, and more than 6 cups/d.
The reference category was those who consumed 1-2 cups/d, rather than those who abstained from coffee, because persons who abstain are more likely to be at suboptimal health.
“Comparing the health of coffee drinkers to the health of those choosing to abstain from coffee will typically lead to an impression of a health benefit, even if there would not be one,” said Dr. Hypponen.
The researchers obtained total and regional brain volumes from the MRI imaging substudy starting 4-6 years after baseline assessment. They accessed information on incident dementia and stroke using primary care data, hospital admission electronic health records, national death registers, and self-reported medical conditions.
Covariates included socioeconomic, health, and other factors, such as smoking, alcohol and tea consumption, physical activity, stressful life events, and body mass index.
The investigators found that there was a linear inverse association between coffee consumption and total brain volume (fully adjusted beta per cup, –1.42; 95% confidence interval, –1.89 to –0.94), with consistent patterns for gray matter, white matter, and hippocampal volumes.
There was no evidence to support an association with white matter hyperintensity (WMH) volume (beta –0.01; 95% CI, –0.07 to 0.05).
Higher consumption, higher risk
The analysis also revealed a nonlinear association between coffee consumption and the odds of dementia (P nonlinearity = .0001), with slightly higher odds seen with non–coffee drinkers and decaffeinated-coffee drinkers and more notable increases for participants in the highest categories of coffee consumption compared with light coffee drinkers.
After adjustment for all covariates, the odds ratio of dementia among persons in the category of coffee intake was 1.53 (95% CI, 1.28-1.83). After full adjustments, the association with heavy coffee consumption and stroke was not significant, although “we can’t exclude a weak effect,” said Dr. Hypponen.
“For the highest coffee consumption group, the data support an association which may be anywhere from 0% to 37% higher odds of stroke after full adjustment,” she added.
People at risk for hypertension may develop “unpleasant sensations” and stop drinking coffee before a serious adverse event occurs, said Dr. Hypponen. In a previous study, she and her colleagues showed that those who have genetically higher blood pressure tend to drink less coffee than their counterparts without the condition.
“This type of effect might be expected to naturally limit the adverse effects of coffee on the risk of stroke,” said Dr. Hypponen.
The odds remained elevated for participants drinking more than 6 cups/d after the researchers accounted for sleep quality. There were no differences in risk between men and women or by age.
An examination of the consumption of tea, which often contains caffeine, did not show an association with brain volume or the odds of dementia or stroke.
“We don’t know whether the difference between associations seen for coffee and tea intake reflects the difference in related caffeine intake or some other explanation, such as dehydration or effects operating through blood cholesterol,” said Dr. Hypponen.
Although reverse causation is possible, there’s no reason to believe that it is relevant to the study results. Genetic evidence suggests a causal role of higher coffee intake on risk for Alzheimer’s disease. In addition, results of a clinical trial support the association between higher caffeine intake and smaller gray matter volume, said Dr. Hypponen.
The mechanisms linking coffee consumption to brain volumes and dementia are not well established. However, Dr. Hypponen noted that caffeine has been used to induce apoptosis in cancer studies using glial cells.
“Furthermore, adenosine receptors, which mediate many of the effects of caffeine in the brain, have been suggested to influence the release of growth factors, which in turn can have an influence on astrocyte proliferation and angiogenesis in the brain,” she said.
Some types of coffee contain cafestol, which increases blood cholesterol and can have adverse effects though related mechanisms, said Dr. Hypponen.
The mechanism may also involve dehydration, which may have a harmful effect on the brain. The study suggested a correlation between dehydration and high coffee intake. “Of course, if this is the case, it is good news, as then we can do something about it simply by drinking some water every time we have a cup of coffee,” she said.
Misleading conclusions
Coffee contains antioxidants, and although previous studies have suggested it might be beneficial, this hypothesis is “too simplistic,” said Dr. Hypponen. “While coffee is not going to be all ‘bad’ either, there are a lot of controversies and suggestions about beneficial effects of coffee which may not be true, or at least do not reflect the full story.”
If the drinking of coffee is at least partly determined by an individual’s health status, then that would often lead to misleading conclusions in observational studies, said Dr. Hypponen.
“When one uses as a comparison people who already have poor health and who do not drink coffee because of that, coffee intake will by default appear beneficial simply because there are more people with disease among those choosing abstinence,” she said.
Before now, there was “very little evidence about the association between coffee intake and brain morphology,” and the studies that were conducted were relatively small, said Dr. Hypponen.
One of these smaller studies included a group of women aged 13-30 years. It found that coffee consumption was not associated with total brain volumes, but the findings suggested a U-shaped association with hippocampal volume; higher values were seen both for nondrinkers and the groups with higher consumption.
A small study of elderly patients with diabetes showed no evidence of an association with white matter volume, but there was a possible age-dependent association with gray matter volume.
The largest of the earlier studies had results that were very similar to those of the current study, suggesting that increasing coffee intake is associated with smaller hippocampal volumes, said Dr. Hypponen.
One of the study’s limitations included the fact that full dietary information was available only for a subsample and that factors such as dehydration were measured at baseline rather than at the time of brain MRI.
Another possible study limitation was the use of self-reported data and the fact that lifestyle changes may have occurred between baseline and MRI or covariate measurement.
In addition, the study is subject to a healthy-volunteer bias, and its implications are restricted to White British persons. The association needs to be studied in other ethnic populations, the authors noted.
A reason to cut back?
Commenting on the findings, Walter Willett, MD, DrPH, professor of epidemiology and nutrition, Harvard T. H. Chan School of Public Health, Boston, said the study is large and quite well done.
“It does raise questions about an increase in risk of dementia with six or more cups of coffee per day,” said Dr. Willett. “At the same time, it provides reassurance about lack of adverse effects of coffee for those consuming three or four cups per day, and little increase in risk, if any, with five cups per day.”
It’s not entirely clear whether the increase in risk with six or more cups of coffee per day represents a “true effect” of coffee, inasmuch as the study did not seem to adjust fully for dietary factors, high consumption of alcohol, or past smoking, said Dr. Willett.
The findings don’t suggest that coffee lovers should give up their Java. “But six or more cups per day is a lot, and those who drink that much might consider cutting back a bit while research continues,” said Dr. Willett.
The study was supported by the National Health and Medical Research Council.
A version of this article first appeared on Medscape.com.
FROM NUTRITIONAL NEUROSCIENCE
Reducing air pollution is linked to slowed brain aging and lower dementia risk
, new research reveals. The findings have implications for individual behaviors, such as avoiding areas with poor air quality, but they also have implications for public policy, said study investigator, Xinhui Wang, PhD, assistant professor of research neurology, department of neurology, University of Southern California, Los Angeles.
“Controlling air quality has great benefits not only for the short-term, for example for pulmonary function or very broadly mortality, but can impact brain function and slow memory function decline and in the long run may reduce dementia cases.”
The findings were presented at the 2021 Alzheimer’s Association International Conference.
New approach
Previous research examining the impact of reducing air pollution, which has primarily examined respiratory illnesses and mortality, showed it is beneficial. However, no previous studies have examined the impact of improved air quality on cognitive function.
The current study used a subset of participants from the Women’s Health Initiative Memory Study-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO), which evaluated whether postmenopausal women derive cognitive benefit from hormone therapy.
The analysis included 2,232 community-dwelling older women aged 74-92 (mean age, 81.5 years) who did not have dementia at study enrollment.
Researchers obtained measures of participants’ annual cognitive function from 2008 to 2018. These measures included general cognitive status assessed using the Telephone Interview for Cognitive Status-modified (TICSm) and episodic memory assessed by the telephone-based California Verbal Learning Test (CVLT).
The investigators used complex geographical covariates to estimate exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2), in areas where individual participants lived from 1996 to 2012. The investigators averaged measures over 3-year periods immediately preceding (recent exposure) and 10 years prior to (remote exposure) enrollment, then calculated individual-level improvements in air quality as the reduction from remote to recent exposures.
The researchers examined pollution exposure and cognitive outcomes at different times to determine causation.
“Maybe the relationship isn’t causal and is just an association, so we tried to separate the timeframe for exposure and outcome and make sure the exposure was before we measured the outcome,” said Dr. Wang.
The investigators adjusted for multiple sociodemographic, lifestyle, and clinical characteristics.
Reduced dementia risk
The analysis showed air quality improved significantly for both PM2.5 and NO2 before study enrollment. “For almost 95% of the subjects in our study, air quality improved over the 10 years,” said Dr. Wang.
During a median follow-up of 6.2 years, there was a significant decline in cognitive status and episodic memory in study participants, which makes sense, said Dr. Wang, because cognitive function naturally declines with age.
However, a 10% improvement in air quality PM2.5 and NO2 resulted in a respective 14% and 26% decreased risk for dementia. This translates into a level of risk seen in women 2 to 3 years younger.
Greater air quality improvement was associated with slower decline in both general cognitive status and episodic memory.
“Participants all declined in cognitive function, but living in areas with the greatest air quality improvement slowed this decline,” said Dr. Wang.
“Whether you look at global cognitive function or memory-specific function, and whether you look at PM2.5 or NO2, slower decline was in the range of someone who is 1-2 years younger.”
The associations did not significantly differ by age, region, education, APOE ε4 genotypes, or cardiovascular risk factors.
Patients concerned about cognitive decline can take steps to avoid exposure to pollution by wearing a mask; avoiding heavy traffic, fires, and smoke; or moving to an area with better air quality, said Dr. Wang.
“But our study mainly tried to provide some evidence for policymakers and regulators,” she added.
Another study carried out by the same investigators suggests pollution may affect various cognitive functions differently. This analysis used the same cohort, timeframe, and air quality improvement indicators as the first study but examined the association with specific cognitive domains, including episodic memory, working memory, attention/executive function, and language.
The investigators found women living in locations with greater PM2.5 improvement performed better on tests of episodic memory (P = .002), working memory (P = .01) and attention/executive function (P = .01), but not language. Findings were similar for improved NO2.
When looking at air quality improvement and trajectory slopes of decline across cognitive functions, only the association between improved NO2 and slower episodic memory decline was statistically significant (P < 0.001). “The other domains were marginal or not significant,” said Dr. Wang.
“This suggests that brain regions are impacted differently,” she said, adding that various brain areas oversee different cognitive functions.
Important policy implications
Commenting on the research, Rebecca Edelmayer, PhD, senior director of scientific engagement, Alzheimer’s Association, said she welcomes new research on environmental factors that affect Alzheimer’s disease.
Whereas previous studies have linked longterm air pollution exposure to accumulation of Alzheimer’s disease-related brain plaques and increased risk of dementia, “these newer studies provide some of the first evidence to suggest that actually reducing pollution is associated with lower risk of all-cause dementia,” said Dr. Edelmayer.
Individuals can control some factors that contribute to dementia risk, such as exercise, diet, and physical activity, but it’s more difficult for them to control exposure to smog and pollution, she said.
“This is probably going to require changes to policy from federal and local governments and businesses, to start addressing the need to improve air quality to help reduce risk for dementia.”
A version of this article first appeared on Medscape.com.
, new research reveals. The findings have implications for individual behaviors, such as avoiding areas with poor air quality, but they also have implications for public policy, said study investigator, Xinhui Wang, PhD, assistant professor of research neurology, department of neurology, University of Southern California, Los Angeles.
“Controlling air quality has great benefits not only for the short-term, for example for pulmonary function or very broadly mortality, but can impact brain function and slow memory function decline and in the long run may reduce dementia cases.”
The findings were presented at the 2021 Alzheimer’s Association International Conference.
New approach
Previous research examining the impact of reducing air pollution, which has primarily examined respiratory illnesses and mortality, showed it is beneficial. However, no previous studies have examined the impact of improved air quality on cognitive function.
The current study used a subset of participants from the Women’s Health Initiative Memory Study-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO), which evaluated whether postmenopausal women derive cognitive benefit from hormone therapy.
The analysis included 2,232 community-dwelling older women aged 74-92 (mean age, 81.5 years) who did not have dementia at study enrollment.
Researchers obtained measures of participants’ annual cognitive function from 2008 to 2018. These measures included general cognitive status assessed using the Telephone Interview for Cognitive Status-modified (TICSm) and episodic memory assessed by the telephone-based California Verbal Learning Test (CVLT).
The investigators used complex geographical covariates to estimate exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2), in areas where individual participants lived from 1996 to 2012. The investigators averaged measures over 3-year periods immediately preceding (recent exposure) and 10 years prior to (remote exposure) enrollment, then calculated individual-level improvements in air quality as the reduction from remote to recent exposures.
The researchers examined pollution exposure and cognitive outcomes at different times to determine causation.
“Maybe the relationship isn’t causal and is just an association, so we tried to separate the timeframe for exposure and outcome and make sure the exposure was before we measured the outcome,” said Dr. Wang.
The investigators adjusted for multiple sociodemographic, lifestyle, and clinical characteristics.
Reduced dementia risk
The analysis showed air quality improved significantly for both PM2.5 and NO2 before study enrollment. “For almost 95% of the subjects in our study, air quality improved over the 10 years,” said Dr. Wang.
During a median follow-up of 6.2 years, there was a significant decline in cognitive status and episodic memory in study participants, which makes sense, said Dr. Wang, because cognitive function naturally declines with age.
However, a 10% improvement in air quality PM2.5 and NO2 resulted in a respective 14% and 26% decreased risk for dementia. This translates into a level of risk seen in women 2 to 3 years younger.
Greater air quality improvement was associated with slower decline in both general cognitive status and episodic memory.
“Participants all declined in cognitive function, but living in areas with the greatest air quality improvement slowed this decline,” said Dr. Wang.
“Whether you look at global cognitive function or memory-specific function, and whether you look at PM2.5 or NO2, slower decline was in the range of someone who is 1-2 years younger.”
The associations did not significantly differ by age, region, education, APOE ε4 genotypes, or cardiovascular risk factors.
Patients concerned about cognitive decline can take steps to avoid exposure to pollution by wearing a mask; avoiding heavy traffic, fires, and smoke; or moving to an area with better air quality, said Dr. Wang.
“But our study mainly tried to provide some evidence for policymakers and regulators,” she added.
Another study carried out by the same investigators suggests pollution may affect various cognitive functions differently. This analysis used the same cohort, timeframe, and air quality improvement indicators as the first study but examined the association with specific cognitive domains, including episodic memory, working memory, attention/executive function, and language.
The investigators found women living in locations with greater PM2.5 improvement performed better on tests of episodic memory (P = .002), working memory (P = .01) and attention/executive function (P = .01), but not language. Findings were similar for improved NO2.
When looking at air quality improvement and trajectory slopes of decline across cognitive functions, only the association between improved NO2 and slower episodic memory decline was statistically significant (P < 0.001). “The other domains were marginal or not significant,” said Dr. Wang.
“This suggests that brain regions are impacted differently,” she said, adding that various brain areas oversee different cognitive functions.
Important policy implications
Commenting on the research, Rebecca Edelmayer, PhD, senior director of scientific engagement, Alzheimer’s Association, said she welcomes new research on environmental factors that affect Alzheimer’s disease.
Whereas previous studies have linked longterm air pollution exposure to accumulation of Alzheimer’s disease-related brain plaques and increased risk of dementia, “these newer studies provide some of the first evidence to suggest that actually reducing pollution is associated with lower risk of all-cause dementia,” said Dr. Edelmayer.
Individuals can control some factors that contribute to dementia risk, such as exercise, diet, and physical activity, but it’s more difficult for them to control exposure to smog and pollution, she said.
“This is probably going to require changes to policy from federal and local governments and businesses, to start addressing the need to improve air quality to help reduce risk for dementia.”
A version of this article first appeared on Medscape.com.
, new research reveals. The findings have implications for individual behaviors, such as avoiding areas with poor air quality, but they also have implications for public policy, said study investigator, Xinhui Wang, PhD, assistant professor of research neurology, department of neurology, University of Southern California, Los Angeles.
“Controlling air quality has great benefits not only for the short-term, for example for pulmonary function or very broadly mortality, but can impact brain function and slow memory function decline and in the long run may reduce dementia cases.”
The findings were presented at the 2021 Alzheimer’s Association International Conference.
New approach
Previous research examining the impact of reducing air pollution, which has primarily examined respiratory illnesses and mortality, showed it is beneficial. However, no previous studies have examined the impact of improved air quality on cognitive function.
The current study used a subset of participants from the Women’s Health Initiative Memory Study-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO), which evaluated whether postmenopausal women derive cognitive benefit from hormone therapy.
The analysis included 2,232 community-dwelling older women aged 74-92 (mean age, 81.5 years) who did not have dementia at study enrollment.
Researchers obtained measures of participants’ annual cognitive function from 2008 to 2018. These measures included general cognitive status assessed using the Telephone Interview for Cognitive Status-modified (TICSm) and episodic memory assessed by the telephone-based California Verbal Learning Test (CVLT).
The investigators used complex geographical covariates to estimate exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2), in areas where individual participants lived from 1996 to 2012. The investigators averaged measures over 3-year periods immediately preceding (recent exposure) and 10 years prior to (remote exposure) enrollment, then calculated individual-level improvements in air quality as the reduction from remote to recent exposures.
The researchers examined pollution exposure and cognitive outcomes at different times to determine causation.
“Maybe the relationship isn’t causal and is just an association, so we tried to separate the timeframe for exposure and outcome and make sure the exposure was before we measured the outcome,” said Dr. Wang.
The investigators adjusted for multiple sociodemographic, lifestyle, and clinical characteristics.
Reduced dementia risk
The analysis showed air quality improved significantly for both PM2.5 and NO2 before study enrollment. “For almost 95% of the subjects in our study, air quality improved over the 10 years,” said Dr. Wang.
During a median follow-up of 6.2 years, there was a significant decline in cognitive status and episodic memory in study participants, which makes sense, said Dr. Wang, because cognitive function naturally declines with age.
However, a 10% improvement in air quality PM2.5 and NO2 resulted in a respective 14% and 26% decreased risk for dementia. This translates into a level of risk seen in women 2 to 3 years younger.
Greater air quality improvement was associated with slower decline in both general cognitive status and episodic memory.
“Participants all declined in cognitive function, but living in areas with the greatest air quality improvement slowed this decline,” said Dr. Wang.
“Whether you look at global cognitive function or memory-specific function, and whether you look at PM2.5 or NO2, slower decline was in the range of someone who is 1-2 years younger.”
The associations did not significantly differ by age, region, education, APOE ε4 genotypes, or cardiovascular risk factors.
Patients concerned about cognitive decline can take steps to avoid exposure to pollution by wearing a mask; avoiding heavy traffic, fires, and smoke; or moving to an area with better air quality, said Dr. Wang.
“But our study mainly tried to provide some evidence for policymakers and regulators,” she added.
Another study carried out by the same investigators suggests pollution may affect various cognitive functions differently. This analysis used the same cohort, timeframe, and air quality improvement indicators as the first study but examined the association with specific cognitive domains, including episodic memory, working memory, attention/executive function, and language.
The investigators found women living in locations with greater PM2.5 improvement performed better on tests of episodic memory (P = .002), working memory (P = .01) and attention/executive function (P = .01), but not language. Findings were similar for improved NO2.
When looking at air quality improvement and trajectory slopes of decline across cognitive functions, only the association between improved NO2 and slower episodic memory decline was statistically significant (P < 0.001). “The other domains were marginal or not significant,” said Dr. Wang.
“This suggests that brain regions are impacted differently,” she said, adding that various brain areas oversee different cognitive functions.
Important policy implications
Commenting on the research, Rebecca Edelmayer, PhD, senior director of scientific engagement, Alzheimer’s Association, said she welcomes new research on environmental factors that affect Alzheimer’s disease.
Whereas previous studies have linked longterm air pollution exposure to accumulation of Alzheimer’s disease-related brain plaques and increased risk of dementia, “these newer studies provide some of the first evidence to suggest that actually reducing pollution is associated with lower risk of all-cause dementia,” said Dr. Edelmayer.
Individuals can control some factors that contribute to dementia risk, such as exercise, diet, and physical activity, but it’s more difficult for them to control exposure to smog and pollution, she said.
“This is probably going to require changes to policy from federal and local governments and businesses, to start addressing the need to improve air quality to help reduce risk for dementia.”
A version of this article first appeared on Medscape.com.
From AAIC 2021
Twofold increased risk for death from COVID-19 in psych patients
compared with those without a psychiatric diagnosis, according to the results of the largest study of its kind to date.
These findings, the investigators noted, highlight the need to prioritize vaccination in patients with preexisting mental health disorders.
“We have proven beyond a shadow of a doubt that there are increased risks” among psychiatric patients who get COVID-19, study investigator Livia De Picker, MD, PhD, psychiatrist and postdoctoral researcher, University Psychiatric Hospital Campus Duffel and University of Antwerp (Belgium), told this news organization.
“Doctors need to look at these patients the same way they would other high-risk people, for example those with diabetes or chronic obstructive pulmonary disease,” all of whom should be protected against COVID-19, Dr. De Picker added.
The study was published online July 15, 2021, in Lancet Psychiatry.
Risk by mental illness type
The systematic review included 33 studies from 22 countries that reported risk estimates for mortality, hospitalization, and ICU admission in patients with confirmed SARS-CoV-2 infection. The meta-analysis included 23 of these studies with a total of 1.47 million participants. Of these, 43,938 had a psychiatric disorder.
The primary outcome was mortality after COVID-19. Secondary outcomes included hospitalization and ICU admission after COVID-19. Researchers adjusted for age, sex, and other covariates.
Results showed the presence of any comorbid mental illness was associated with an increased risk for death after SARS-CoV-2 infection (odds ratio, 2.00; 95% confidence interval, 1.58-2.54; P < .0001).
When researchers stratified mortality risk by psychiatric disorder type, the most robust associations were for psychotic and mood disorders. Substance use disorders, intellectual disabilities, and developmental disorders were associated with higher mortality only in crude estimates. There was no increased death risk associated with anxiety disorders.
“That there are differences between the various types of disorders was an interesting finding,” said Dr. De Picker, adding that previous research “just lumped together all diagnostic categories.”
Potential mechanisms
The study did not explore why psychiatric illness raise the risk for death in the setting of COVID-19, so potential mechanisms are purely speculative. However, the investigators believe it may reflect biological processes such as immune-inflammatory alterations.
Psychotic disorders and mood disorders in particular, are associated with immune changes, including immunogenetic abnormalities, raised cytokine concentrations, autoantibodies, acute-phase proteins, and aberrant counts of leukocyte cell types, said Dr. De Picker.
She likened this to elderly people being at increased risk following COVID-19 because their immune system is compromised and less able to fight infection.
There are likely other factors at play, said Dr. De Picker. These could include social isolation and lifestyle factors like poor diet, physical inactivity, high alcohol and tobacco use, and sleep disturbances.
In addition, psychiatric patients have a higher prevalence of comorbidities including diabetes, cardiovascular disease, and respiratory disease, which could also play a role.
The increased mortality might also reflect reduced access to care. “Some of these patients may be living in difficult socioeconomic conditions,” said Dr. De Picker.
She noted that, while the in-hospital mortality was not increased, the risk was significantly increased in samples that were outside of the hospital. This reinforces the need for providing close monitoring and early referral to hospital for psychiatric patients with COVID-19.
Mortality varied significantly among countries, with the lowest risk in Europe and the United States. This difference might be attributable to differences in health care systems and access to care, said Dr. De Picker.
Overall, the risk for hospitalization was about double for COVID patients with a mental illness, but when stratified by disorder, there was only a significantly increased risk for substance use and mood disorders. “But mood disorders were not even significant any more after adjusting for age, sex, and comorbid conditions, and we don’t see an increased risk for psychotic disorders whereas they had the highest mortality risks,” said Dr. De Picker.
Psych meds a risk factor?
The studies were primarily based on electronic medical records, so investigators were unable to carry out “a fine grain analysis” into clinical factors affecting outcomes, she noted.
Antipsychotics were consistently associated with an increased risk for mortality (adjusted OR, 2.43; 95% CI, 1.81-3.25), as were anxiolytics (aOR, 1.47; 95% CI, 1.15-1.88).
“There are some theoretical reasons why we believe there could be a risk associated with these drugs,” said Dr. De Picker. For example, antipsychotics can increase the risk for cardiac arrhythmias and thromboembolic events, and cause interactions with drugs used to treat COVID-19.
As for anxiolytics, especially benzodiazepines, these drugs are associated with respiratory risk and with all-cause mortality. “So you could imagine that someone who is infected with a respiratory virus and [is] then using these drugs on top of that would have a worse outcome,” said Dr. De Picker.
In contrast to antipsychotics and anxiolytics, antidepressants did not increase mortality risk.
Dr. De Picker noted a new study by French researchers showing a protective effect of certain serotonergic antidepressants on COVID outcomes, including mortality.
There was no robust evidence of an increased risk for ICU admission for patients with mental disorders. However, the authors noted some studies included small samples of patients with psychiatric disorders, “contributing to a low certainty of evidence for ICU admission.”
Dr. De Picker criticized COVID vaccine policies that don’t prioritize patients with psychiatric disorders. In many countries, groups that were initially green-lighted for the vaccine included health care workers, the elderly, and those with underlying conditions such as diabetes, obesity and even mild hypertension – but not mental illness, which is also an underlying risk.
‘Outstanding’ research
Commenting on the study for this news organization, Jonathan E. Alpert, MD, PhD, department of psychiatry and behavioral sciences, Montefiore Medical Center, New York, and chair of the American Psychiatric Association Council on Research, called it “outstanding” and the largest of its kind.
“There have been a number of studies that have come to similar conclusions, that people with psychiatric illness are at greater risk for poorer outcomes, but because any given study had a relatively limited sample, perhaps from one health system or one country, there were some inconsistencies,” said Dr. Alpert.
“This is the strongest report so far that has made the point that people with psychiatric illness are a vulnerable population for a negative outcome from COVID, including the most worrisome – mortality.”
The study helps drive home a “very important public health lesson” that applies to COVID-19 but goes “beyond,” said Dr. Alpert.
“As a society, we need to keep in mind that people with serious mental disorders are a vulnerable population for poorer outcomes in most general medical conditions,” he stressed, “whether it’s cancer or heart disease or diabetes, and special efforts need to be made to reach out to those populations.”
Dr. Alpert agreed that, at the start of the pandemic, psychiatric patients in the United States were not prioritized for vaccination, and although psychiatric patients may initially have found it difficult to navigate the health care system to learn where and how to get a COVID shot, today that barrier has mostly been removed.
“Our patients are at least as willing as any other subgroup to get the vaccine, and that includes people with psychotic disorders,” he said.
The study was supported by the European College of Neuropsychopharmacology Immuno-NeuroPsychiatry network and Fondazione Centro San Raffaele (Milan). Dr. De Picker reported receiving grants from Boehringer Ingelheim and Janssen outside the submitted work. She is a member of the European College of Neuropsychopharmacology Immuno-NeuroPsychiatry Thematic Working Group.
A version of this article first appeared on Medscape.com.
compared with those without a psychiatric diagnosis, according to the results of the largest study of its kind to date.
These findings, the investigators noted, highlight the need to prioritize vaccination in patients with preexisting mental health disorders.
“We have proven beyond a shadow of a doubt that there are increased risks” among psychiatric patients who get COVID-19, study investigator Livia De Picker, MD, PhD, psychiatrist and postdoctoral researcher, University Psychiatric Hospital Campus Duffel and University of Antwerp (Belgium), told this news organization.
“Doctors need to look at these patients the same way they would other high-risk people, for example those with diabetes or chronic obstructive pulmonary disease,” all of whom should be protected against COVID-19, Dr. De Picker added.
The study was published online July 15, 2021, in Lancet Psychiatry.
Risk by mental illness type
The systematic review included 33 studies from 22 countries that reported risk estimates for mortality, hospitalization, and ICU admission in patients with confirmed SARS-CoV-2 infection. The meta-analysis included 23 of these studies with a total of 1.47 million participants. Of these, 43,938 had a psychiatric disorder.
The primary outcome was mortality after COVID-19. Secondary outcomes included hospitalization and ICU admission after COVID-19. Researchers adjusted for age, sex, and other covariates.
Results showed the presence of any comorbid mental illness was associated with an increased risk for death after SARS-CoV-2 infection (odds ratio, 2.00; 95% confidence interval, 1.58-2.54; P < .0001).
When researchers stratified mortality risk by psychiatric disorder type, the most robust associations were for psychotic and mood disorders. Substance use disorders, intellectual disabilities, and developmental disorders were associated with higher mortality only in crude estimates. There was no increased death risk associated with anxiety disorders.
“That there are differences between the various types of disorders was an interesting finding,” said Dr. De Picker, adding that previous research “just lumped together all diagnostic categories.”
Potential mechanisms
The study did not explore why psychiatric illness raise the risk for death in the setting of COVID-19, so potential mechanisms are purely speculative. However, the investigators believe it may reflect biological processes such as immune-inflammatory alterations.
Psychotic disorders and mood disorders in particular, are associated with immune changes, including immunogenetic abnormalities, raised cytokine concentrations, autoantibodies, acute-phase proteins, and aberrant counts of leukocyte cell types, said Dr. De Picker.
She likened this to elderly people being at increased risk following COVID-19 because their immune system is compromised and less able to fight infection.
There are likely other factors at play, said Dr. De Picker. These could include social isolation and lifestyle factors like poor diet, physical inactivity, high alcohol and tobacco use, and sleep disturbances.
In addition, psychiatric patients have a higher prevalence of comorbidities including diabetes, cardiovascular disease, and respiratory disease, which could also play a role.
The increased mortality might also reflect reduced access to care. “Some of these patients may be living in difficult socioeconomic conditions,” said Dr. De Picker.
She noted that, while the in-hospital mortality was not increased, the risk was significantly increased in samples that were outside of the hospital. This reinforces the need for providing close monitoring and early referral to hospital for psychiatric patients with COVID-19.
Mortality varied significantly among countries, with the lowest risk in Europe and the United States. This difference might be attributable to differences in health care systems and access to care, said Dr. De Picker.
Overall, the risk for hospitalization was about double for COVID patients with a mental illness, but when stratified by disorder, there was only a significantly increased risk for substance use and mood disorders. “But mood disorders were not even significant any more after adjusting for age, sex, and comorbid conditions, and we don’t see an increased risk for psychotic disorders whereas they had the highest mortality risks,” said Dr. De Picker.
Psych meds a risk factor?
The studies were primarily based on electronic medical records, so investigators were unable to carry out “a fine grain analysis” into clinical factors affecting outcomes, she noted.
Antipsychotics were consistently associated with an increased risk for mortality (adjusted OR, 2.43; 95% CI, 1.81-3.25), as were anxiolytics (aOR, 1.47; 95% CI, 1.15-1.88).
“There are some theoretical reasons why we believe there could be a risk associated with these drugs,” said Dr. De Picker. For example, antipsychotics can increase the risk for cardiac arrhythmias and thromboembolic events, and cause interactions with drugs used to treat COVID-19.
As for anxiolytics, especially benzodiazepines, these drugs are associated with respiratory risk and with all-cause mortality. “So you could imagine that someone who is infected with a respiratory virus and [is] then using these drugs on top of that would have a worse outcome,” said Dr. De Picker.
In contrast to antipsychotics and anxiolytics, antidepressants did not increase mortality risk.
Dr. De Picker noted a new study by French researchers showing a protective effect of certain serotonergic antidepressants on COVID outcomes, including mortality.
There was no robust evidence of an increased risk for ICU admission for patients with mental disorders. However, the authors noted some studies included small samples of patients with psychiatric disorders, “contributing to a low certainty of evidence for ICU admission.”
Dr. De Picker criticized COVID vaccine policies that don’t prioritize patients with psychiatric disorders. In many countries, groups that were initially green-lighted for the vaccine included health care workers, the elderly, and those with underlying conditions such as diabetes, obesity and even mild hypertension – but not mental illness, which is also an underlying risk.
‘Outstanding’ research
Commenting on the study for this news organization, Jonathan E. Alpert, MD, PhD, department of psychiatry and behavioral sciences, Montefiore Medical Center, New York, and chair of the American Psychiatric Association Council on Research, called it “outstanding” and the largest of its kind.
“There have been a number of studies that have come to similar conclusions, that people with psychiatric illness are at greater risk for poorer outcomes, but because any given study had a relatively limited sample, perhaps from one health system or one country, there were some inconsistencies,” said Dr. Alpert.
“This is the strongest report so far that has made the point that people with psychiatric illness are a vulnerable population for a negative outcome from COVID, including the most worrisome – mortality.”
The study helps drive home a “very important public health lesson” that applies to COVID-19 but goes “beyond,” said Dr. Alpert.
“As a society, we need to keep in mind that people with serious mental disorders are a vulnerable population for poorer outcomes in most general medical conditions,” he stressed, “whether it’s cancer or heart disease or diabetes, and special efforts need to be made to reach out to those populations.”
Dr. Alpert agreed that, at the start of the pandemic, psychiatric patients in the United States were not prioritized for vaccination, and although psychiatric patients may initially have found it difficult to navigate the health care system to learn where and how to get a COVID shot, today that barrier has mostly been removed.
“Our patients are at least as willing as any other subgroup to get the vaccine, and that includes people with psychotic disorders,” he said.
The study was supported by the European College of Neuropsychopharmacology Immuno-NeuroPsychiatry network and Fondazione Centro San Raffaele (Milan). Dr. De Picker reported receiving grants from Boehringer Ingelheim and Janssen outside the submitted work. She is a member of the European College of Neuropsychopharmacology Immuno-NeuroPsychiatry Thematic Working Group.
A version of this article first appeared on Medscape.com.
compared with those without a psychiatric diagnosis, according to the results of the largest study of its kind to date.
These findings, the investigators noted, highlight the need to prioritize vaccination in patients with preexisting mental health disorders.
“We have proven beyond a shadow of a doubt that there are increased risks” among psychiatric patients who get COVID-19, study investigator Livia De Picker, MD, PhD, psychiatrist and postdoctoral researcher, University Psychiatric Hospital Campus Duffel and University of Antwerp (Belgium), told this news organization.
“Doctors need to look at these patients the same way they would other high-risk people, for example those with diabetes or chronic obstructive pulmonary disease,” all of whom should be protected against COVID-19, Dr. De Picker added.
The study was published online July 15, 2021, in Lancet Psychiatry.
Risk by mental illness type
The systematic review included 33 studies from 22 countries that reported risk estimates for mortality, hospitalization, and ICU admission in patients with confirmed SARS-CoV-2 infection. The meta-analysis included 23 of these studies with a total of 1.47 million participants. Of these, 43,938 had a psychiatric disorder.
The primary outcome was mortality after COVID-19. Secondary outcomes included hospitalization and ICU admission after COVID-19. Researchers adjusted for age, sex, and other covariates.
Results showed the presence of any comorbid mental illness was associated with an increased risk for death after SARS-CoV-2 infection (odds ratio, 2.00; 95% confidence interval, 1.58-2.54; P < .0001).
When researchers stratified mortality risk by psychiatric disorder type, the most robust associations were for psychotic and mood disorders. Substance use disorders, intellectual disabilities, and developmental disorders were associated with higher mortality only in crude estimates. There was no increased death risk associated with anxiety disorders.
“That there are differences between the various types of disorders was an interesting finding,” said Dr. De Picker, adding that previous research “just lumped together all diagnostic categories.”
Potential mechanisms
The study did not explore why psychiatric illness raise the risk for death in the setting of COVID-19, so potential mechanisms are purely speculative. However, the investigators believe it may reflect biological processes such as immune-inflammatory alterations.
Psychotic disorders and mood disorders in particular, are associated with immune changes, including immunogenetic abnormalities, raised cytokine concentrations, autoantibodies, acute-phase proteins, and aberrant counts of leukocyte cell types, said Dr. De Picker.
She likened this to elderly people being at increased risk following COVID-19 because their immune system is compromised and less able to fight infection.
There are likely other factors at play, said Dr. De Picker. These could include social isolation and lifestyle factors like poor diet, physical inactivity, high alcohol and tobacco use, and sleep disturbances.
In addition, psychiatric patients have a higher prevalence of comorbidities including diabetes, cardiovascular disease, and respiratory disease, which could also play a role.
The increased mortality might also reflect reduced access to care. “Some of these patients may be living in difficult socioeconomic conditions,” said Dr. De Picker.
She noted that, while the in-hospital mortality was not increased, the risk was significantly increased in samples that were outside of the hospital. This reinforces the need for providing close monitoring and early referral to hospital for psychiatric patients with COVID-19.
Mortality varied significantly among countries, with the lowest risk in Europe and the United States. This difference might be attributable to differences in health care systems and access to care, said Dr. De Picker.
Overall, the risk for hospitalization was about double for COVID patients with a mental illness, but when stratified by disorder, there was only a significantly increased risk for substance use and mood disorders. “But mood disorders were not even significant any more after adjusting for age, sex, and comorbid conditions, and we don’t see an increased risk for psychotic disorders whereas they had the highest mortality risks,” said Dr. De Picker.
Psych meds a risk factor?
The studies were primarily based on electronic medical records, so investigators were unable to carry out “a fine grain analysis” into clinical factors affecting outcomes, she noted.
Antipsychotics were consistently associated with an increased risk for mortality (adjusted OR, 2.43; 95% CI, 1.81-3.25), as were anxiolytics (aOR, 1.47; 95% CI, 1.15-1.88).
“There are some theoretical reasons why we believe there could be a risk associated with these drugs,” said Dr. De Picker. For example, antipsychotics can increase the risk for cardiac arrhythmias and thromboembolic events, and cause interactions with drugs used to treat COVID-19.
As for anxiolytics, especially benzodiazepines, these drugs are associated with respiratory risk and with all-cause mortality. “So you could imagine that someone who is infected with a respiratory virus and [is] then using these drugs on top of that would have a worse outcome,” said Dr. De Picker.
In contrast to antipsychotics and anxiolytics, antidepressants did not increase mortality risk.
Dr. De Picker noted a new study by French researchers showing a protective effect of certain serotonergic antidepressants on COVID outcomes, including mortality.
There was no robust evidence of an increased risk for ICU admission for patients with mental disorders. However, the authors noted some studies included small samples of patients with psychiatric disorders, “contributing to a low certainty of evidence for ICU admission.”
Dr. De Picker criticized COVID vaccine policies that don’t prioritize patients with psychiatric disorders. In many countries, groups that were initially green-lighted for the vaccine included health care workers, the elderly, and those with underlying conditions such as diabetes, obesity and even mild hypertension – but not mental illness, which is also an underlying risk.
‘Outstanding’ research
Commenting on the study for this news organization, Jonathan E. Alpert, MD, PhD, department of psychiatry and behavioral sciences, Montefiore Medical Center, New York, and chair of the American Psychiatric Association Council on Research, called it “outstanding” and the largest of its kind.
“There have been a number of studies that have come to similar conclusions, that people with psychiatric illness are at greater risk for poorer outcomes, but because any given study had a relatively limited sample, perhaps from one health system or one country, there were some inconsistencies,” said Dr. Alpert.
“This is the strongest report so far that has made the point that people with psychiatric illness are a vulnerable population for a negative outcome from COVID, including the most worrisome – mortality.”
The study helps drive home a “very important public health lesson” that applies to COVID-19 but goes “beyond,” said Dr. Alpert.
“As a society, we need to keep in mind that people with serious mental disorders are a vulnerable population for poorer outcomes in most general medical conditions,” he stressed, “whether it’s cancer or heart disease or diabetes, and special efforts need to be made to reach out to those populations.”
Dr. Alpert agreed that, at the start of the pandemic, psychiatric patients in the United States were not prioritized for vaccination, and although psychiatric patients may initially have found it difficult to navigate the health care system to learn where and how to get a COVID shot, today that barrier has mostly been removed.
“Our patients are at least as willing as any other subgroup to get the vaccine, and that includes people with psychotic disorders,” he said.
The study was supported by the European College of Neuropsychopharmacology Immuno-NeuroPsychiatry network and Fondazione Centro San Raffaele (Milan). Dr. De Picker reported receiving grants from Boehringer Ingelheim and Janssen outside the submitted work. She is a member of the European College of Neuropsychopharmacology Immuno-NeuroPsychiatry Thematic Working Group.
A version of this article first appeared on Medscape.com.
State-of-the-art psych unit designed with recovery in mind
Calming wall colors, nature-themed murals, and soft nighttime lighting are all part of a unique new state-of-the-art inpatient psychiatric unit that focuses especially on children and adolescents who have experienced significant trauma.
The 16-bed unit, which has been in the works for 3½ years and opened June 30 at the University of Maryland Medical Center (UMMC), in Baltimore, Maryland, treats youth aged 5 to 17 years. It has separate wings for younger children and for adolescents.
“We offer a really warm and welcoming environment that we think is going to promote health and healing,” the unit’s head, Sarah Edwards, DO, director of child and adolescent psychiatry at UMMC and assistant professor of psychiatry, University of Maryland School of Medicine (UMSOM), Baltimore, said in an interview.
Previous research shows that 1 in 4 children experience some kind of maltreatment, whether physical, sexual, or emotional, and that 1 in 5 develop a diagnosable mental health disorder.
, Dr. Edwards noted. Recent data show that the rate of suicidal ideation among youth has increased significantly during the COVID-19 crisis.
“Urban children have unfortunately suffered a lot of what we call traumatic stress, so they might be victims of physical or sexual abuse but also face layers of stressful situations – for example, living in unsafe neighborhoods and attending schools that might not be so welcoming and safe,” said Dr. Edwards.
Safety first
Typical conditions treated at the new unit will include depression, anxiety, attention-deficit/hyperactivity disorder, psychotic spectrum, as well as trauma disorders.
Some of these young patients have been through the foster care system and show signs of trauma and poor attachment, Dr. Edwards noted. As a result, they may have difficulty regulating their thoughts and emotions and at times exhibit dangerous behavior.
The new unit is designed both architecturally and clinically to deliver “trauma-informed” care. This type of approach “recognizes the pervasive nature of trauma” and promotes settings that facilitate recovery, Dr. Edwards added.
The idea is to treat individuals “in a way that doesn’t re-traumatize them or make their condition worse,” she added.
Safety is of the utmost importance in the unit, Jill RachBeisel, MD, chief of psychiatry at UMMC and professor and chair in the department of psychiatry at UMSOM, said in an interview.
“Health care workers must recognize and respond to the effects of trauma – and one very important way is to provide care in settings that emphasize physical and emotional safety, which helps instill a sense of control and empowerment,” Dr. RachBeisel said.
Providing youth with options is an important way to provide that sense of control, Dr. Edwards added. For example, residents can choose their own music in their bedroom, such as sounds of nature, running water, or birds chirping. They can also draw or write personal notes on a large whiteboard in their unit.
Circadian-rhythm lighting
Other unique elements of the new unit include walls painted soothing shades and murals of natural scenery, created by a local artist.
These murals perfectly capture “the kind of overall spirit of what we were trying to induce,” said Dr. Edwards.
A part of the unit dubbed the “front porch” has a large mural depicting “a landscape of beautiful trees and water and animals,” she noted. Kids can gather here to relax or just hang out.
The lighting at the unit mirrors circadian rhythms. It’s brighter during the day to promote wakefulness and participation in activities and gradually dims toward the evening hours to help induce restful nighttime sleep.
Safe and empowering and adopt productive behaviors and coping skills, Dr. Edwards noted.
The staff for the interprofessional unit includes psychiatrists, psychologists, psychiatric nurses, occupational therapists, and others trained in pediatric care.
Advice for other centers
“Our new unit is designed to provide the highest standard in mental health care and incorporates a high-tech approach to create a calming, soothing, and engaging setting,” said Dr. RachBeisel.
School-transition specialists help connect discharged patients and their families to vital services and peer support. These services represent “an essential component of the continuum of care” for youth experiencing mental distress, she added.
Other organizations considering establishing a similar type of psychiatric unit should consult all stakeholders.
“We had staff, no matter what their role, be part of every step of this process, including helping with the design, picking out furniture they thought would make the most sense, and helping choose the artwork,” she said.
It is also important to incorporate feedback from youth themselves, Dr. Edwards added.
A version of this article first appeared on Medscape.com.
Calming wall colors, nature-themed murals, and soft nighttime lighting are all part of a unique new state-of-the-art inpatient psychiatric unit that focuses especially on children and adolescents who have experienced significant trauma.
The 16-bed unit, which has been in the works for 3½ years and opened June 30 at the University of Maryland Medical Center (UMMC), in Baltimore, Maryland, treats youth aged 5 to 17 years. It has separate wings for younger children and for adolescents.
“We offer a really warm and welcoming environment that we think is going to promote health and healing,” the unit’s head, Sarah Edwards, DO, director of child and adolescent psychiatry at UMMC and assistant professor of psychiatry, University of Maryland School of Medicine (UMSOM), Baltimore, said in an interview.
Previous research shows that 1 in 4 children experience some kind of maltreatment, whether physical, sexual, or emotional, and that 1 in 5 develop a diagnosable mental health disorder.
, Dr. Edwards noted. Recent data show that the rate of suicidal ideation among youth has increased significantly during the COVID-19 crisis.
“Urban children have unfortunately suffered a lot of what we call traumatic stress, so they might be victims of physical or sexual abuse but also face layers of stressful situations – for example, living in unsafe neighborhoods and attending schools that might not be so welcoming and safe,” said Dr. Edwards.
Safety first
Typical conditions treated at the new unit will include depression, anxiety, attention-deficit/hyperactivity disorder, psychotic spectrum, as well as trauma disorders.
Some of these young patients have been through the foster care system and show signs of trauma and poor attachment, Dr. Edwards noted. As a result, they may have difficulty regulating their thoughts and emotions and at times exhibit dangerous behavior.
The new unit is designed both architecturally and clinically to deliver “trauma-informed” care. This type of approach “recognizes the pervasive nature of trauma” and promotes settings that facilitate recovery, Dr. Edwards added.
The idea is to treat individuals “in a way that doesn’t re-traumatize them or make their condition worse,” she added.
Safety is of the utmost importance in the unit, Jill RachBeisel, MD, chief of psychiatry at UMMC and professor and chair in the department of psychiatry at UMSOM, said in an interview.
“Health care workers must recognize and respond to the effects of trauma – and one very important way is to provide care in settings that emphasize physical and emotional safety, which helps instill a sense of control and empowerment,” Dr. RachBeisel said.
Providing youth with options is an important way to provide that sense of control, Dr. Edwards added. For example, residents can choose their own music in their bedroom, such as sounds of nature, running water, or birds chirping. They can also draw or write personal notes on a large whiteboard in their unit.
Circadian-rhythm lighting
Other unique elements of the new unit include walls painted soothing shades and murals of natural scenery, created by a local artist.
These murals perfectly capture “the kind of overall spirit of what we were trying to induce,” said Dr. Edwards.
A part of the unit dubbed the “front porch” has a large mural depicting “a landscape of beautiful trees and water and animals,” she noted. Kids can gather here to relax or just hang out.
The lighting at the unit mirrors circadian rhythms. It’s brighter during the day to promote wakefulness and participation in activities and gradually dims toward the evening hours to help induce restful nighttime sleep.
Safe and empowering and adopt productive behaviors and coping skills, Dr. Edwards noted.
The staff for the interprofessional unit includes psychiatrists, psychologists, psychiatric nurses, occupational therapists, and others trained in pediatric care.
Advice for other centers
“Our new unit is designed to provide the highest standard in mental health care and incorporates a high-tech approach to create a calming, soothing, and engaging setting,” said Dr. RachBeisel.
School-transition specialists help connect discharged patients and their families to vital services and peer support. These services represent “an essential component of the continuum of care” for youth experiencing mental distress, she added.
Other organizations considering establishing a similar type of psychiatric unit should consult all stakeholders.
“We had staff, no matter what their role, be part of every step of this process, including helping with the design, picking out furniture they thought would make the most sense, and helping choose the artwork,” she said.
It is also important to incorporate feedback from youth themselves, Dr. Edwards added.
A version of this article first appeared on Medscape.com.
Calming wall colors, nature-themed murals, and soft nighttime lighting are all part of a unique new state-of-the-art inpatient psychiatric unit that focuses especially on children and adolescents who have experienced significant trauma.
The 16-bed unit, which has been in the works for 3½ years and opened June 30 at the University of Maryland Medical Center (UMMC), in Baltimore, Maryland, treats youth aged 5 to 17 years. It has separate wings for younger children and for adolescents.
“We offer a really warm and welcoming environment that we think is going to promote health and healing,” the unit’s head, Sarah Edwards, DO, director of child and adolescent psychiatry at UMMC and assistant professor of psychiatry, University of Maryland School of Medicine (UMSOM), Baltimore, said in an interview.
Previous research shows that 1 in 4 children experience some kind of maltreatment, whether physical, sexual, or emotional, and that 1 in 5 develop a diagnosable mental health disorder.
, Dr. Edwards noted. Recent data show that the rate of suicidal ideation among youth has increased significantly during the COVID-19 crisis.
“Urban children have unfortunately suffered a lot of what we call traumatic stress, so they might be victims of physical or sexual abuse but also face layers of stressful situations – for example, living in unsafe neighborhoods and attending schools that might not be so welcoming and safe,” said Dr. Edwards.
Safety first
Typical conditions treated at the new unit will include depression, anxiety, attention-deficit/hyperactivity disorder, psychotic spectrum, as well as trauma disorders.
Some of these young patients have been through the foster care system and show signs of trauma and poor attachment, Dr. Edwards noted. As a result, they may have difficulty regulating their thoughts and emotions and at times exhibit dangerous behavior.
The new unit is designed both architecturally and clinically to deliver “trauma-informed” care. This type of approach “recognizes the pervasive nature of trauma” and promotes settings that facilitate recovery, Dr. Edwards added.
The idea is to treat individuals “in a way that doesn’t re-traumatize them or make their condition worse,” she added.
Safety is of the utmost importance in the unit, Jill RachBeisel, MD, chief of psychiatry at UMMC and professor and chair in the department of psychiatry at UMSOM, said in an interview.
“Health care workers must recognize and respond to the effects of trauma – and one very important way is to provide care in settings that emphasize physical and emotional safety, which helps instill a sense of control and empowerment,” Dr. RachBeisel said.
Providing youth with options is an important way to provide that sense of control, Dr. Edwards added. For example, residents can choose their own music in their bedroom, such as sounds of nature, running water, or birds chirping. They can also draw or write personal notes on a large whiteboard in their unit.
Circadian-rhythm lighting
Other unique elements of the new unit include walls painted soothing shades and murals of natural scenery, created by a local artist.
These murals perfectly capture “the kind of overall spirit of what we were trying to induce,” said Dr. Edwards.
A part of the unit dubbed the “front porch” has a large mural depicting “a landscape of beautiful trees and water and animals,” she noted. Kids can gather here to relax or just hang out.
The lighting at the unit mirrors circadian rhythms. It’s brighter during the day to promote wakefulness and participation in activities and gradually dims toward the evening hours to help induce restful nighttime sleep.
Safe and empowering and adopt productive behaviors and coping skills, Dr. Edwards noted.
The staff for the interprofessional unit includes psychiatrists, psychologists, psychiatric nurses, occupational therapists, and others trained in pediatric care.
Advice for other centers
“Our new unit is designed to provide the highest standard in mental health care and incorporates a high-tech approach to create a calming, soothing, and engaging setting,” said Dr. RachBeisel.
School-transition specialists help connect discharged patients and their families to vital services and peer support. These services represent “an essential component of the continuum of care” for youth experiencing mental distress, she added.
Other organizations considering establishing a similar type of psychiatric unit should consult all stakeholders.
“We had staff, no matter what their role, be part of every step of this process, including helping with the design, picking out furniture they thought would make the most sense, and helping choose the artwork,” she said.
It is also important to incorporate feedback from youth themselves, Dr. Edwards added.
A version of this article first appeared on Medscape.com.
A less expensive, more convenient treatment option for MS?
Patients with multiple sclerosis (MS) may soon have another less expensive, more convenient treatment option compared with other agents in the same drug class, new research suggests.
The positive results suggest “another strong and reasonably safe medication might be available to increase the repertoire of effective medicines that we can offer MS patients,” said Lawrence Steinman, MD, professor of neurology, Stanford (Calif.) University. “These are delightful data in my opinion,” he added.
The findings were presented at the 2021 Congress of the European Academy of Neurology.
‘Glycoengineered’ antibody
If approved by the U.S. Food and Drug Administration, ublituximab would become the only glycoengineered anti-CD20 monoclonal antibody for MS. Glycoengineering involves changing protein-associated carbohydrates to alter pharmacokinetic properties.
There are currently two approved anti-CD20 agents for MS, but both require 4-hour infusions. For many patients, this means “at least half their day is shot,” Dr. Steinman said. “A lot of people don’t want to or can’t miss a half day of work.” Ublituximab can be infused more rapidly, he noted.
For the study, the investigators analyzed data from the ULTIMATE I and ULTIMATE II studies, which included 1,089 mostly White patients with MS. Almost all participants had the relapsing-remitting form of the disease and were between 18 and 55 years of age (average age, 36 years). Their scores on the Expanded Disability Status Scale (EDSS) were from 0 to 5.5, and they had been neurologically stable for at least 30 days prior to screening.
Participants were required to have experienced two or more relapses within the previous 2 years or one or more relapses in the year prior and/or had one gadolinium-enhancing lesion in the year prior to screening.
The study population was mostly from the Ukraine and Russia. It is more difficult to recruit patients into MS drug studies in the United States and Western Europe because many patients in these countries are already receiving approved drugs, which deters enrollment, explained Dr. Steinman.
Investigators randomly assigned the participants to receive the investigational drug or 14 mg of oral teriflunomide, a drug that blocks the proliferation of immune cells, once daily. The ublituximab group received an initial infusion of 150 mg over 4 hours and then a 1-hour infusion of 450 mg every 6 months over the course of the 96-week study.
Primary outcomes met
For ULTIMATE I, the primary outcome was ARR. Results showed that this rate was 0.076 for the ublituximab group and 0.188 for the teriflunomide group, resulting in a 60% relative reduction (adjusted ARR ratio, 0.406; 95% confidence interval, 0.268-0.615; P < .0001).
In ULTIMATE II, the ARR was 0.091 for ublituximab and 0.178 for teriflunomide, for a relative reduction of 49% (ARR ratio, 0.509; 95% CI, 0.330-0.784; P = .0022).
One way of interpreting these data is that patients are likely to have only one relapse in 10 years, said Dr. Steinman. “So that was very good news.”
It is not clear why relative reductions for ARR differed between the two studies; “probably the real number is somewhere between 60% and 49%,” Dr. Steinman said.
From MRI scans, the total number of relevant lesions was reduced by 97% with ublituximab compared with teriflunomide in ULTIMATE I and by 96% in trial II.
Another “piece of really good news” from the studies is that the drug led to a significant improvement in disability, rather than “just slowing it down,” Dr. Steinman noted.
There was a 116% increased chance of confirmed disability improvement (CDI) with ublituximab versus teriflunomide in the first trial (P = .003) and a 103% increased chance of CDI in the second trial (P = .0026).
The percentage of patients who had no evidence of disease activity was 198% for the patients who received the trial drug in comparison with the control group in trial I and 277% in trial II (P < .0001 for both trials).
A life changer?
Dr. Steinman said the “robust” findings suggest that patients with MS “won’t have a relapse and will improve. Those are two pretty good messages for somebody with this wretched disease.”
The investigational drug was generally well tolerated. The percentage of adverse events (AEs) with the study drug was about the same as with the comparator. About 9.5% of the ublituximab group had a serious AE, compared with 6.2% of the teriflunomide group.
The ublituximab group had more infections (4.0% vs. 2.6%), which Dr. Steinman said is not surprising because the drug is a potent immune suppressant. “It’s an unfortunate consequence of this kind of strong biologic that knocks down a whole arm of the immune system. The wonder to me is that these are still rather infrequent,” he said.
If approved, “it will be interesting to see how regulatory agencies handle this in terms of risk mitigation,” said Dr. Steinman. He added that a warning label might be a consideration.
However, the safety of this drug “is certainly acceptable,” said Dr. Steinman. “In general, this drug is not that different from the other drugs in the class of anti-CD20s.”
Dr. Steinman noted that he understands why some patients prefer an oral drug and may have an “aversion to getting stuck with a needle,” but he pointed out that teriflunomide has some drawbacks. For example, it tends to thin hair.
“For people who have had relapses, people who are unable to do what they want to in life – attend school, hold down jobs, exercise – this new drug could really be life changing,” he said.
He added that he would “strongly urge” his own family and relatives, if they had MS, to take one of the anti-CD20 drugs.
Ublituximab also has a number of advantages over the other agents in the same class. Not only does it work well, have an acceptable safety profile, and require a shorter infusion time, but it could also be less costly, Dr. Steinman noted. “The company has said it intends to come in at a lower price point,” he said.
The company is now planning to prepare a biological license application for use in MS. Interestingly, the drug, in combination with umbralisib (Ukoniq), is already under review by the FDA for use in chronic lymphoctytic leukemia and small lymphocytic lymphoma.
Striking improvement
When session chair Marcello Moccio, MD, Multiple Sclerosis Clinical Care and Research Center, Federico II University, Naples, Italy, asked Dr. Steinman to elaborate on the “very strong effect” of the drug with regard to improving disability, Dr. Steinman said the improvement was “striking.”
Being able to talk to patients about possible improvement rather than about delaying disability “is really gratifying” and provides a “much more constructive and optimistic outlook,” he said.
He noted that as physicians improve their management of patients with MS “and are paying attention to things that we haven’t over the years, like vitamin D and even mental health,” disability progression management “is getting better.”
Dr. Steinman is a consultant for TG Therapeutics.
A version of this article first appeared on Medscape.com.
Patients with multiple sclerosis (MS) may soon have another less expensive, more convenient treatment option compared with other agents in the same drug class, new research suggests.
The positive results suggest “another strong and reasonably safe medication might be available to increase the repertoire of effective medicines that we can offer MS patients,” said Lawrence Steinman, MD, professor of neurology, Stanford (Calif.) University. “These are delightful data in my opinion,” he added.
The findings were presented at the 2021 Congress of the European Academy of Neurology.
‘Glycoengineered’ antibody
If approved by the U.S. Food and Drug Administration, ublituximab would become the only glycoengineered anti-CD20 monoclonal antibody for MS. Glycoengineering involves changing protein-associated carbohydrates to alter pharmacokinetic properties.
There are currently two approved anti-CD20 agents for MS, but both require 4-hour infusions. For many patients, this means “at least half their day is shot,” Dr. Steinman said. “A lot of people don’t want to or can’t miss a half day of work.” Ublituximab can be infused more rapidly, he noted.
For the study, the investigators analyzed data from the ULTIMATE I and ULTIMATE II studies, which included 1,089 mostly White patients with MS. Almost all participants had the relapsing-remitting form of the disease and were between 18 and 55 years of age (average age, 36 years). Their scores on the Expanded Disability Status Scale (EDSS) were from 0 to 5.5, and they had been neurologically stable for at least 30 days prior to screening.
Participants were required to have experienced two or more relapses within the previous 2 years or one or more relapses in the year prior and/or had one gadolinium-enhancing lesion in the year prior to screening.
The study population was mostly from the Ukraine and Russia. It is more difficult to recruit patients into MS drug studies in the United States and Western Europe because many patients in these countries are already receiving approved drugs, which deters enrollment, explained Dr. Steinman.
Investigators randomly assigned the participants to receive the investigational drug or 14 mg of oral teriflunomide, a drug that blocks the proliferation of immune cells, once daily. The ublituximab group received an initial infusion of 150 mg over 4 hours and then a 1-hour infusion of 450 mg every 6 months over the course of the 96-week study.
Primary outcomes met
For ULTIMATE I, the primary outcome was ARR. Results showed that this rate was 0.076 for the ublituximab group and 0.188 for the teriflunomide group, resulting in a 60% relative reduction (adjusted ARR ratio, 0.406; 95% confidence interval, 0.268-0.615; P < .0001).
In ULTIMATE II, the ARR was 0.091 for ublituximab and 0.178 for teriflunomide, for a relative reduction of 49% (ARR ratio, 0.509; 95% CI, 0.330-0.784; P = .0022).
One way of interpreting these data is that patients are likely to have only one relapse in 10 years, said Dr. Steinman. “So that was very good news.”
It is not clear why relative reductions for ARR differed between the two studies; “probably the real number is somewhere between 60% and 49%,” Dr. Steinman said.
From MRI scans, the total number of relevant lesions was reduced by 97% with ublituximab compared with teriflunomide in ULTIMATE I and by 96% in trial II.
Another “piece of really good news” from the studies is that the drug led to a significant improvement in disability, rather than “just slowing it down,” Dr. Steinman noted.
There was a 116% increased chance of confirmed disability improvement (CDI) with ublituximab versus teriflunomide in the first trial (P = .003) and a 103% increased chance of CDI in the second trial (P = .0026).
The percentage of patients who had no evidence of disease activity was 198% for the patients who received the trial drug in comparison with the control group in trial I and 277% in trial II (P < .0001 for both trials).
A life changer?
Dr. Steinman said the “robust” findings suggest that patients with MS “won’t have a relapse and will improve. Those are two pretty good messages for somebody with this wretched disease.”
The investigational drug was generally well tolerated. The percentage of adverse events (AEs) with the study drug was about the same as with the comparator. About 9.5% of the ublituximab group had a serious AE, compared with 6.2% of the teriflunomide group.
The ublituximab group had more infections (4.0% vs. 2.6%), which Dr. Steinman said is not surprising because the drug is a potent immune suppressant. “It’s an unfortunate consequence of this kind of strong biologic that knocks down a whole arm of the immune system. The wonder to me is that these are still rather infrequent,” he said.
If approved, “it will be interesting to see how regulatory agencies handle this in terms of risk mitigation,” said Dr. Steinman. He added that a warning label might be a consideration.
However, the safety of this drug “is certainly acceptable,” said Dr. Steinman. “In general, this drug is not that different from the other drugs in the class of anti-CD20s.”
Dr. Steinman noted that he understands why some patients prefer an oral drug and may have an “aversion to getting stuck with a needle,” but he pointed out that teriflunomide has some drawbacks. For example, it tends to thin hair.
“For people who have had relapses, people who are unable to do what they want to in life – attend school, hold down jobs, exercise – this new drug could really be life changing,” he said.
He added that he would “strongly urge” his own family and relatives, if they had MS, to take one of the anti-CD20 drugs.
Ublituximab also has a number of advantages over the other agents in the same class. Not only does it work well, have an acceptable safety profile, and require a shorter infusion time, but it could also be less costly, Dr. Steinman noted. “The company has said it intends to come in at a lower price point,” he said.
The company is now planning to prepare a biological license application for use in MS. Interestingly, the drug, in combination with umbralisib (Ukoniq), is already under review by the FDA for use in chronic lymphoctytic leukemia and small lymphocytic lymphoma.
Striking improvement
When session chair Marcello Moccio, MD, Multiple Sclerosis Clinical Care and Research Center, Federico II University, Naples, Italy, asked Dr. Steinman to elaborate on the “very strong effect” of the drug with regard to improving disability, Dr. Steinman said the improvement was “striking.”
Being able to talk to patients about possible improvement rather than about delaying disability “is really gratifying” and provides a “much more constructive and optimistic outlook,” he said.
He noted that as physicians improve their management of patients with MS “and are paying attention to things that we haven’t over the years, like vitamin D and even mental health,” disability progression management “is getting better.”
Dr. Steinman is a consultant for TG Therapeutics.
A version of this article first appeared on Medscape.com.
Patients with multiple sclerosis (MS) may soon have another less expensive, more convenient treatment option compared with other agents in the same drug class, new research suggests.
The positive results suggest “another strong and reasonably safe medication might be available to increase the repertoire of effective medicines that we can offer MS patients,” said Lawrence Steinman, MD, professor of neurology, Stanford (Calif.) University. “These are delightful data in my opinion,” he added.
The findings were presented at the 2021 Congress of the European Academy of Neurology.
‘Glycoengineered’ antibody
If approved by the U.S. Food and Drug Administration, ublituximab would become the only glycoengineered anti-CD20 monoclonal antibody for MS. Glycoengineering involves changing protein-associated carbohydrates to alter pharmacokinetic properties.
There are currently two approved anti-CD20 agents for MS, but both require 4-hour infusions. For many patients, this means “at least half their day is shot,” Dr. Steinman said. “A lot of people don’t want to or can’t miss a half day of work.” Ublituximab can be infused more rapidly, he noted.
For the study, the investigators analyzed data from the ULTIMATE I and ULTIMATE II studies, which included 1,089 mostly White patients with MS. Almost all participants had the relapsing-remitting form of the disease and were between 18 and 55 years of age (average age, 36 years). Their scores on the Expanded Disability Status Scale (EDSS) were from 0 to 5.5, and they had been neurologically stable for at least 30 days prior to screening.
Participants were required to have experienced two or more relapses within the previous 2 years or one or more relapses in the year prior and/or had one gadolinium-enhancing lesion in the year prior to screening.
The study population was mostly from the Ukraine and Russia. It is more difficult to recruit patients into MS drug studies in the United States and Western Europe because many patients in these countries are already receiving approved drugs, which deters enrollment, explained Dr. Steinman.
Investigators randomly assigned the participants to receive the investigational drug or 14 mg of oral teriflunomide, a drug that blocks the proliferation of immune cells, once daily. The ublituximab group received an initial infusion of 150 mg over 4 hours and then a 1-hour infusion of 450 mg every 6 months over the course of the 96-week study.
Primary outcomes met
For ULTIMATE I, the primary outcome was ARR. Results showed that this rate was 0.076 for the ublituximab group and 0.188 for the teriflunomide group, resulting in a 60% relative reduction (adjusted ARR ratio, 0.406; 95% confidence interval, 0.268-0.615; P < .0001).
In ULTIMATE II, the ARR was 0.091 for ublituximab and 0.178 for teriflunomide, for a relative reduction of 49% (ARR ratio, 0.509; 95% CI, 0.330-0.784; P = .0022).
One way of interpreting these data is that patients are likely to have only one relapse in 10 years, said Dr. Steinman. “So that was very good news.”
It is not clear why relative reductions for ARR differed between the two studies; “probably the real number is somewhere between 60% and 49%,” Dr. Steinman said.
From MRI scans, the total number of relevant lesions was reduced by 97% with ublituximab compared with teriflunomide in ULTIMATE I and by 96% in trial II.
Another “piece of really good news” from the studies is that the drug led to a significant improvement in disability, rather than “just slowing it down,” Dr. Steinman noted.
There was a 116% increased chance of confirmed disability improvement (CDI) with ublituximab versus teriflunomide in the first trial (P = .003) and a 103% increased chance of CDI in the second trial (P = .0026).
The percentage of patients who had no evidence of disease activity was 198% for the patients who received the trial drug in comparison with the control group in trial I and 277% in trial II (P < .0001 for both trials).
A life changer?
Dr. Steinman said the “robust” findings suggest that patients with MS “won’t have a relapse and will improve. Those are two pretty good messages for somebody with this wretched disease.”
The investigational drug was generally well tolerated. The percentage of adverse events (AEs) with the study drug was about the same as with the comparator. About 9.5% of the ublituximab group had a serious AE, compared with 6.2% of the teriflunomide group.
The ublituximab group had more infections (4.0% vs. 2.6%), which Dr. Steinman said is not surprising because the drug is a potent immune suppressant. “It’s an unfortunate consequence of this kind of strong biologic that knocks down a whole arm of the immune system. The wonder to me is that these are still rather infrequent,” he said.
If approved, “it will be interesting to see how regulatory agencies handle this in terms of risk mitigation,” said Dr. Steinman. He added that a warning label might be a consideration.
However, the safety of this drug “is certainly acceptable,” said Dr. Steinman. “In general, this drug is not that different from the other drugs in the class of anti-CD20s.”
Dr. Steinman noted that he understands why some patients prefer an oral drug and may have an “aversion to getting stuck with a needle,” but he pointed out that teriflunomide has some drawbacks. For example, it tends to thin hair.
“For people who have had relapses, people who are unable to do what they want to in life – attend school, hold down jobs, exercise – this new drug could really be life changing,” he said.
He added that he would “strongly urge” his own family and relatives, if they had MS, to take one of the anti-CD20 drugs.
Ublituximab also has a number of advantages over the other agents in the same class. Not only does it work well, have an acceptable safety profile, and require a shorter infusion time, but it could also be less costly, Dr. Steinman noted. “The company has said it intends to come in at a lower price point,” he said.
The company is now planning to prepare a biological license application for use in MS. Interestingly, the drug, in combination with umbralisib (Ukoniq), is already under review by the FDA for use in chronic lymphoctytic leukemia and small lymphocytic lymphoma.
Striking improvement
When session chair Marcello Moccio, MD, Multiple Sclerosis Clinical Care and Research Center, Federico II University, Naples, Italy, asked Dr. Steinman to elaborate on the “very strong effect” of the drug with regard to improving disability, Dr. Steinman said the improvement was “striking.”
Being able to talk to patients about possible improvement rather than about delaying disability “is really gratifying” and provides a “much more constructive and optimistic outlook,” he said.
He noted that as physicians improve their management of patients with MS “and are paying attention to things that we haven’t over the years, like vitamin D and even mental health,” disability progression management “is getting better.”
Dr. Steinman is a consultant for TG Therapeutics.
A version of this article first appeared on Medscape.com.
From EAN 2021
Dose-dependent effect of ‘internet addiction’ and sleep problems
More evidence suggests the severity of internet addiction (IA) is directly related to the severity of sleep problems in youth.
Results from a study of more than 4,000 adolescent students show IA severity was linked to less sleep and to daytime sleepiness. In addition, boys aged 12-14 years who were addicted to computer games versus social media networking were the most affected.
Sleep issues could be “easily detectable manifestations of pathological internet addiction,” investigator Sergey Tereshchenko, PhD, Scientific Research Institute for Medical Problems of the North, Krasnoyask State Medical University, Russia, told this news organization.
These sleep problems require attention and correction, Dr. Tereshchenko added.
The findings were presented at the virtual Congress of the European Academy of Neurology 2021.
New phenomenon
IA is a relatively new psychological phenomenon and is most prevalent in “socially vulnerable groups,” such as adolescents, Dr. Tereshchenko said.
He cited numerous studies that have “convincingly demonstrated” IA is comorbid with a broad range of psychopathologic conditions, including depression, anxiety, and attention deficit hyperactivity disorder.
There is also growing evidence, including from systematic reviews in 2014 and 2019, that IA affects a wide range of sleep parameters.
However, most studies in adolescents have used only one psychometric tool to assess addiction, revealing only the “general IA pattern” and not the type of IA, Dr. Tereshchenko noted.
Adolescents may not be addicted to the internet itself but to certain behaviors like gaming or social networking, he said.
The “undoubted advantage” of his team’s research is the use of more than one tool, making it possible to “verify the predominant content of the addiction,” he added.
The investigators previously assessed general prevalence of IA in adolescents in Siberia and found about 6.8% of participants displayed pathological IA behavior – and that gaming addiction is more common in boys whereas addiction to social networking is more common in girls.
This prevalence rate is lower than in the Philippines (21.1%), Hong Kong (16.4%), Malaysia (14.1%), China (11%), and South Korea (9.7%), but slightly higher than in Japan (6.2%).
IA prevalence among adolescents in Europe ranges from 1% to 11%, with an average of 4.4%, said Dr. Tereshchenko.
Siberian students’ sleep
The current study included 4,344 students aged 12-18 years (average age, about 15 years) from 10 public schools in three large cities of Central Siberia (Krasnoyarsk, Abakan, and Kyzyl). There were slightly more girls than boys in the study sample.
Participants completed the Russian language version of the Chen Internet Addiction Scale (CIAS), which covers five symptomatic criteria for addictive behavior: withdrawal symptoms, signs of tolerance, compulsive use, psychological or physical problems, and difficulty managing time.
In this questionnaire, respondents rate several statements regarding the effect of internet use, each on a 4-point Likert scale: not at all (1 point), a little bit (2 points), moderately (3 points) and extremely (4). The total score ranges from 26 to 104.
A CIAS score of 26-42 indicates adaptive internet use, 43-64 indicates maladaptive internet use, and 65 and above indicates pathological internet use (PIU), which was classified as “internet-addicted.”
The researchers also used the nine-item Social Media Disorder Scale, as well as the Pittsburgh Sleep Quality Index to assess nighttime sleep.
Among other questions, teens were asked how long it usually took them to fall asleep and when they typically went to bed and woke up on school nights.
For daytime sleepiness, investigators used the targeted Pediatric Daytime Sleepiness Scale questionnaire, making them among the few research groups to use this psychometric instrument, Dr. Tereshchenko noted.
After parental consent was given, students completed the tests at the end of the day’s lessons. Total test time was about 45 minutes.
Sleep disturbance
Initial study results showed that compared with the other groups, adolescents with PIU tended to go to bed later, wake up later, take longer to fall asleep, sleep less at night, have more nighttime awakenings, and have more daytime sleepiness.
Sleep quality was the most impaired in boys aged 12-14 years who are addicted to internet computer games.
“In this group, 5 of the 6 sleep assessment parameters we studied were changed,” Dr. Tereshchenko reported.
Decreased total nighttime sleep was more common in older adolescents.
On average, boys and girls aged 15-18 years got less than the recommended 8 hours of sleep per night. Boys with IA got only about 6.4 hours per night and girls with IA got about 6.6 hours.
Interestingly, IA is generally more prevalent among teen girls than boys in Russia, which is not the case in Europe and North America, Dr. Tereshchenko noted.
Mechanisms linking IA and sleep disorders are not clear, but the relationship is probably multifactorial and perhaps interrelated, creating something of a “vicious circle,” he said.
“Sleep disturbances, which reflect psychosocial problems, depression, and anxiety-phobic disorders, can precede and contribute to IA. On the other hand, sleep disturbances such as insomnia can lead to increased use of the internet in the evening and at night, further exacerbating the problem,” said Dr. Tereshchenko.
Research is lacking on useful treatments for youth with IA, but these kids would likely benefit from behavioral therapy approaches, he added.
No escape?
Commenting on the study for this news organization, Maurice M. Ohayon, MD, DSc, PhD, director of the Stanford Sleep Epidemiology Research Center, Stanford University, California, said the topic of youth IA is “very important.”
Previous research in this field has shown a major impact from IA not only on sleep but also on mood – with irritability, depression, and even thoughts of suicide being possible red flags, said Dr. Ohayon, who was not involved in the current study.
Interestingly, his own research has also found that young teenage boys are most at risk for gaming addiction.
Although internet gaming has some positive effects, such as fostering leadership skills and relationships, it has become increasingly violent and isolating, with more adult professional gamers preying on younger players, Dr. Ohayon said.
“The major problem is that it’s putting children in a virtual world from which it’s difficult to escape,” he added.
Dr. Ohayon also noted concern about future developmental effects in kids who play video games for hours on end without coming out of their bedroom and with no physical contact with fellow players.
Parents should intervene before this situation occurs and limit the time their children spend on the gaming console, he said.
A version of this article first appeared on Medscape.com.
More evidence suggests the severity of internet addiction (IA) is directly related to the severity of sleep problems in youth.
Results from a study of more than 4,000 adolescent students show IA severity was linked to less sleep and to daytime sleepiness. In addition, boys aged 12-14 years who were addicted to computer games versus social media networking were the most affected.
Sleep issues could be “easily detectable manifestations of pathological internet addiction,” investigator Sergey Tereshchenko, PhD, Scientific Research Institute for Medical Problems of the North, Krasnoyask State Medical University, Russia, told this news organization.
These sleep problems require attention and correction, Dr. Tereshchenko added.
The findings were presented at the virtual Congress of the European Academy of Neurology 2021.
New phenomenon
IA is a relatively new psychological phenomenon and is most prevalent in “socially vulnerable groups,” such as adolescents, Dr. Tereshchenko said.
He cited numerous studies that have “convincingly demonstrated” IA is comorbid with a broad range of psychopathologic conditions, including depression, anxiety, and attention deficit hyperactivity disorder.
There is also growing evidence, including from systematic reviews in 2014 and 2019, that IA affects a wide range of sleep parameters.
However, most studies in adolescents have used only one psychometric tool to assess addiction, revealing only the “general IA pattern” and not the type of IA, Dr. Tereshchenko noted.
Adolescents may not be addicted to the internet itself but to certain behaviors like gaming or social networking, he said.
The “undoubted advantage” of his team’s research is the use of more than one tool, making it possible to “verify the predominant content of the addiction,” he added.
The investigators previously assessed general prevalence of IA in adolescents in Siberia and found about 6.8% of participants displayed pathological IA behavior – and that gaming addiction is more common in boys whereas addiction to social networking is more common in girls.
This prevalence rate is lower than in the Philippines (21.1%), Hong Kong (16.4%), Malaysia (14.1%), China (11%), and South Korea (9.7%), but slightly higher than in Japan (6.2%).
IA prevalence among adolescents in Europe ranges from 1% to 11%, with an average of 4.4%, said Dr. Tereshchenko.
Siberian students’ sleep
The current study included 4,344 students aged 12-18 years (average age, about 15 years) from 10 public schools in three large cities of Central Siberia (Krasnoyarsk, Abakan, and Kyzyl). There were slightly more girls than boys in the study sample.
Participants completed the Russian language version of the Chen Internet Addiction Scale (CIAS), which covers five symptomatic criteria for addictive behavior: withdrawal symptoms, signs of tolerance, compulsive use, psychological or physical problems, and difficulty managing time.
In this questionnaire, respondents rate several statements regarding the effect of internet use, each on a 4-point Likert scale: not at all (1 point), a little bit (2 points), moderately (3 points) and extremely (4). The total score ranges from 26 to 104.
A CIAS score of 26-42 indicates adaptive internet use, 43-64 indicates maladaptive internet use, and 65 and above indicates pathological internet use (PIU), which was classified as “internet-addicted.”
The researchers also used the nine-item Social Media Disorder Scale, as well as the Pittsburgh Sleep Quality Index to assess nighttime sleep.
Among other questions, teens were asked how long it usually took them to fall asleep and when they typically went to bed and woke up on school nights.
For daytime sleepiness, investigators used the targeted Pediatric Daytime Sleepiness Scale questionnaire, making them among the few research groups to use this psychometric instrument, Dr. Tereshchenko noted.
After parental consent was given, students completed the tests at the end of the day’s lessons. Total test time was about 45 minutes.
Sleep disturbance
Initial study results showed that compared with the other groups, adolescents with PIU tended to go to bed later, wake up later, take longer to fall asleep, sleep less at night, have more nighttime awakenings, and have more daytime sleepiness.
Sleep quality was the most impaired in boys aged 12-14 years who are addicted to internet computer games.
“In this group, 5 of the 6 sleep assessment parameters we studied were changed,” Dr. Tereshchenko reported.
Decreased total nighttime sleep was more common in older adolescents.
On average, boys and girls aged 15-18 years got less than the recommended 8 hours of sleep per night. Boys with IA got only about 6.4 hours per night and girls with IA got about 6.6 hours.
Interestingly, IA is generally more prevalent among teen girls than boys in Russia, which is not the case in Europe and North America, Dr. Tereshchenko noted.
Mechanisms linking IA and sleep disorders are not clear, but the relationship is probably multifactorial and perhaps interrelated, creating something of a “vicious circle,” he said.
“Sleep disturbances, which reflect psychosocial problems, depression, and anxiety-phobic disorders, can precede and contribute to IA. On the other hand, sleep disturbances such as insomnia can lead to increased use of the internet in the evening and at night, further exacerbating the problem,” said Dr. Tereshchenko.
Research is lacking on useful treatments for youth with IA, but these kids would likely benefit from behavioral therapy approaches, he added.
No escape?
Commenting on the study for this news organization, Maurice M. Ohayon, MD, DSc, PhD, director of the Stanford Sleep Epidemiology Research Center, Stanford University, California, said the topic of youth IA is “very important.”
Previous research in this field has shown a major impact from IA not only on sleep but also on mood – with irritability, depression, and even thoughts of suicide being possible red flags, said Dr. Ohayon, who was not involved in the current study.
Interestingly, his own research has also found that young teenage boys are most at risk for gaming addiction.
Although internet gaming has some positive effects, such as fostering leadership skills and relationships, it has become increasingly violent and isolating, with more adult professional gamers preying on younger players, Dr. Ohayon said.
“The major problem is that it’s putting children in a virtual world from which it’s difficult to escape,” he added.
Dr. Ohayon also noted concern about future developmental effects in kids who play video games for hours on end without coming out of their bedroom and with no physical contact with fellow players.
Parents should intervene before this situation occurs and limit the time their children spend on the gaming console, he said.
A version of this article first appeared on Medscape.com.
More evidence suggests the severity of internet addiction (IA) is directly related to the severity of sleep problems in youth.
Results from a study of more than 4,000 adolescent students show IA severity was linked to less sleep and to daytime sleepiness. In addition, boys aged 12-14 years who were addicted to computer games versus social media networking were the most affected.
Sleep issues could be “easily detectable manifestations of pathological internet addiction,” investigator Sergey Tereshchenko, PhD, Scientific Research Institute for Medical Problems of the North, Krasnoyask State Medical University, Russia, told this news organization.
These sleep problems require attention and correction, Dr. Tereshchenko added.
The findings were presented at the virtual Congress of the European Academy of Neurology 2021.
New phenomenon
IA is a relatively new psychological phenomenon and is most prevalent in “socially vulnerable groups,” such as adolescents, Dr. Tereshchenko said.
He cited numerous studies that have “convincingly demonstrated” IA is comorbid with a broad range of psychopathologic conditions, including depression, anxiety, and attention deficit hyperactivity disorder.
There is also growing evidence, including from systematic reviews in 2014 and 2019, that IA affects a wide range of sleep parameters.
However, most studies in adolescents have used only one psychometric tool to assess addiction, revealing only the “general IA pattern” and not the type of IA, Dr. Tereshchenko noted.
Adolescents may not be addicted to the internet itself but to certain behaviors like gaming or social networking, he said.
The “undoubted advantage” of his team’s research is the use of more than one tool, making it possible to “verify the predominant content of the addiction,” he added.
The investigators previously assessed general prevalence of IA in adolescents in Siberia and found about 6.8% of participants displayed pathological IA behavior – and that gaming addiction is more common in boys whereas addiction to social networking is more common in girls.
This prevalence rate is lower than in the Philippines (21.1%), Hong Kong (16.4%), Malaysia (14.1%), China (11%), and South Korea (9.7%), but slightly higher than in Japan (6.2%).
IA prevalence among adolescents in Europe ranges from 1% to 11%, with an average of 4.4%, said Dr. Tereshchenko.
Siberian students’ sleep
The current study included 4,344 students aged 12-18 years (average age, about 15 years) from 10 public schools in three large cities of Central Siberia (Krasnoyarsk, Abakan, and Kyzyl). There were slightly more girls than boys in the study sample.
Participants completed the Russian language version of the Chen Internet Addiction Scale (CIAS), which covers five symptomatic criteria for addictive behavior: withdrawal symptoms, signs of tolerance, compulsive use, psychological or physical problems, and difficulty managing time.
In this questionnaire, respondents rate several statements regarding the effect of internet use, each on a 4-point Likert scale: not at all (1 point), a little bit (2 points), moderately (3 points) and extremely (4). The total score ranges from 26 to 104.
A CIAS score of 26-42 indicates adaptive internet use, 43-64 indicates maladaptive internet use, and 65 and above indicates pathological internet use (PIU), which was classified as “internet-addicted.”
The researchers also used the nine-item Social Media Disorder Scale, as well as the Pittsburgh Sleep Quality Index to assess nighttime sleep.
Among other questions, teens were asked how long it usually took them to fall asleep and when they typically went to bed and woke up on school nights.
For daytime sleepiness, investigators used the targeted Pediatric Daytime Sleepiness Scale questionnaire, making them among the few research groups to use this psychometric instrument, Dr. Tereshchenko noted.
After parental consent was given, students completed the tests at the end of the day’s lessons. Total test time was about 45 minutes.
Sleep disturbance
Initial study results showed that compared with the other groups, adolescents with PIU tended to go to bed later, wake up later, take longer to fall asleep, sleep less at night, have more nighttime awakenings, and have more daytime sleepiness.
Sleep quality was the most impaired in boys aged 12-14 years who are addicted to internet computer games.
“In this group, 5 of the 6 sleep assessment parameters we studied were changed,” Dr. Tereshchenko reported.
Decreased total nighttime sleep was more common in older adolescents.
On average, boys and girls aged 15-18 years got less than the recommended 8 hours of sleep per night. Boys with IA got only about 6.4 hours per night and girls with IA got about 6.6 hours.
Interestingly, IA is generally more prevalent among teen girls than boys in Russia, which is not the case in Europe and North America, Dr. Tereshchenko noted.
Mechanisms linking IA and sleep disorders are not clear, but the relationship is probably multifactorial and perhaps interrelated, creating something of a “vicious circle,” he said.
“Sleep disturbances, which reflect psychosocial problems, depression, and anxiety-phobic disorders, can precede and contribute to IA. On the other hand, sleep disturbances such as insomnia can lead to increased use of the internet in the evening and at night, further exacerbating the problem,” said Dr. Tereshchenko.
Research is lacking on useful treatments for youth with IA, but these kids would likely benefit from behavioral therapy approaches, he added.
No escape?
Commenting on the study for this news organization, Maurice M. Ohayon, MD, DSc, PhD, director of the Stanford Sleep Epidemiology Research Center, Stanford University, California, said the topic of youth IA is “very important.”
Previous research in this field has shown a major impact from IA not only on sleep but also on mood – with irritability, depression, and even thoughts of suicide being possible red flags, said Dr. Ohayon, who was not involved in the current study.
Interestingly, his own research has also found that young teenage boys are most at risk for gaming addiction.
Although internet gaming has some positive effects, such as fostering leadership skills and relationships, it has become increasingly violent and isolating, with more adult professional gamers preying on younger players, Dr. Ohayon said.
“The major problem is that it’s putting children in a virtual world from which it’s difficult to escape,” he added.
Dr. Ohayon also noted concern about future developmental effects in kids who play video games for hours on end without coming out of their bedroom and with no physical contact with fellow players.
Parents should intervene before this situation occurs and limit the time their children spend on the gaming console, he said.
A version of this article first appeared on Medscape.com.
Noted ability of Mozart’s music to reduce seizures explained?
– and now researchers believe they know why.
Investigators conducting new research found that the acoustic characteristics of Mozart’s Sonata for Two Pianos in D Major (K448) suppresses brain activity in patients with epilepsy, while a piece by the 18th century classical composer Franz Joseph Haydn did not have this effect.
Listening to this Mozart sonata and perhaps other musical pieces may eventually become a treatment for preventing epileptic seizures, said study investigator Ivan Rektor, MD, CSc, Epilepsy Centre at the Hospital St. Anne and professor at the Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
“This research into the impact of listening to music could lead to the development of a music-related type of palliative neurostimulation therapy,” said Dr. Rektor.
The findings were presented at the 2021 Congress of the European Academy of Neurology and published online in the European Journal of Neurology.
Clinically controversial?
Epilepsy affects 6 million people in Europe. Furthermore, estimates show that about 15 million Europeans have had at least one seizure at some time in their lives. In addition, about 30% of patients with epilepsy are not adequately treated with antiseizure medications.
Researchers have been studying the impact of Mozart’s music on brain-wave activity since the 1990s. Various studies report a reduction in epileptiform discharges in patients with epileptic seizures, coma, and refractory nonconvulsive status.
A 2012 meta-analysis of 12 publications involving patients with epilepsy showed an overall reduction in the number of interictal epileptic discharges (IEDs) or abnormal electrical brain waves in 84% of participants who listened to Mozart’s music. A more recent meta-analysis also showed a significant reduction in epileptic seizures and IEDs.
American researchers also found Mozart’s music regulated abnormal interictal epileptiform activity (IEA), especially in those with a high baseline rate of interictal spikes.
However, the methodological quality of some of this research “has been limited,” Dr. Rektor noted. He added that use of music therapy in clinical practice is still considered “controversial.”
The new study included 18 treatment-resistant patients with epilepsy (50% men) who ranged in age from 19 to 55 years. Participants had intracerebral electrodes implanted in the brain before undergoing surgery.
Of the total study population, 15 had temporal lobe epilepsy and three had extratemporal epilepsy. Eleven were affected on the left side, six on the right side, and one bi-temporally. Duration of epilepsy ranged from 8 to 40 years.
Patients listened to the Mozart piece intermittently on one day and to Haydn’s “Surprise” Symphony No. 94 the next day. Researchers counted the number of ED discharges before, during, and after the patients listened to the music.
Surprising finding
Results showed that exposure to the Mozart piece was associated with a 32% reduction in IEDs, from 28 EDs pre-exposure to 19 during exposure. However, IEDs rose to 21 post-exposure.
Overall, the Haydn piece was associated with an increase in IEDs, from 23 pre-exposure to 26 during and post-exposure.
“We saw a clear decrease in epileptic spikes while listening and after listening to Mozart, while there was an increase in spikes while listening to Haydn,” Dr. Rektor said.
He added that all 18 patients responded “more or less” to the music and that the results were statistically significant.
Dr. Rektor noted that the investigators were not surprised by the Mozart effect but were somewhat taken aback by the opposite effect from listening to Haydn.
The impact differed between men and women. The Mozart piece had a larger effect on women. In addition, the Haydn piece led to a decrease in spikes in women but led to “a clear” increase in men, Dr. Rektor reported.
In an effort to explore why the two classical pieces had such different effects, the researchers examined the acoustic properties. They worked with acoustic engineers to examine three musical properties that might influence the number of spikes: rhythm (tempo or beats per minute), dynamics (energy), and timbre (how harsh or unpleasant, how noisy, and how many “high-frequency” parts the music has).
“We observed that K448 [Mozart’s piece] has a more harmonic spectrum and its spectral content doesn’t change quickly, which probably has a positive effect on epilepsy patients,” said Dr. Rektor.
Specific features of the music had a slightly different effect on men and women. Men were more sensitive to dissonance and high-frequency parts while women were more sensitive to energy.
A new theory
Researchers previously hypothesized that the Mozart effect in epilepsy was connected to the emotional impact of music. The neurotransmitter dopamine, which plays a role in the brain’s reward system, is released when listening to music. However, the new research seems to challenge that theory. The majority of the participants did not express a strong preference for classical music.
“We believe emotions didn’t play an important role in these patients,” Dr. Rektor said, adding that the impact was instead mostly related to acoustic signals.
The team also found that the reduction in IEDs was larger in the lateral temporal lobe, the part of the brain involved in translating acoustic signals, rather than in the mesiotemporal limbic region, which plays an important role in the emotional response to music.
Comparing men with women, there’s an “overlap” of brain activation in most brain areas. However, some areas are more activated in men and others in women, said Dr. Rektor.
While the Mozart Sonata for two pianos in D Major has become the “gold standard” in this type of research, Dr. Rektor said “it’s very probable” that other classical compositions with similar acoustic properties have the same effect in epilepsy.
The investigators are testing other musical pieces, both classical and nonclassical. The ultimate aim is to develop individualized musical patterns based on these acoustic features.
“If it works, we would like to use it as a noninvasive neurostimulation method,” Dr. Rektor said.
‘Inspiring research’
Commenting on the study, session chair Marte Bjørk, MD, PhD, associate professor, department of clinical medicine, University of Bergen, Norway, called it “inspiring.” She noted that she recently had a patient whose temporal lobe seizures were consistently triggered by music played on a children’s TV program. “So I have no doubt that music can be important for some patients,” Dr. Bjørk said.
She questioned whether factors other than gender may predict response to music.
The study authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
– and now researchers believe they know why.
Investigators conducting new research found that the acoustic characteristics of Mozart’s Sonata for Two Pianos in D Major (K448) suppresses brain activity in patients with epilepsy, while a piece by the 18th century classical composer Franz Joseph Haydn did not have this effect.
Listening to this Mozart sonata and perhaps other musical pieces may eventually become a treatment for preventing epileptic seizures, said study investigator Ivan Rektor, MD, CSc, Epilepsy Centre at the Hospital St. Anne and professor at the Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
“This research into the impact of listening to music could lead to the development of a music-related type of palliative neurostimulation therapy,” said Dr. Rektor.
The findings were presented at the 2021 Congress of the European Academy of Neurology and published online in the European Journal of Neurology.
Clinically controversial?
Epilepsy affects 6 million people in Europe. Furthermore, estimates show that about 15 million Europeans have had at least one seizure at some time in their lives. In addition, about 30% of patients with epilepsy are not adequately treated with antiseizure medications.
Researchers have been studying the impact of Mozart’s music on brain-wave activity since the 1990s. Various studies report a reduction in epileptiform discharges in patients with epileptic seizures, coma, and refractory nonconvulsive status.
A 2012 meta-analysis of 12 publications involving patients with epilepsy showed an overall reduction in the number of interictal epileptic discharges (IEDs) or abnormal electrical brain waves in 84% of participants who listened to Mozart’s music. A more recent meta-analysis also showed a significant reduction in epileptic seizures and IEDs.
American researchers also found Mozart’s music regulated abnormal interictal epileptiform activity (IEA), especially in those with a high baseline rate of interictal spikes.
However, the methodological quality of some of this research “has been limited,” Dr. Rektor noted. He added that use of music therapy in clinical practice is still considered “controversial.”
The new study included 18 treatment-resistant patients with epilepsy (50% men) who ranged in age from 19 to 55 years. Participants had intracerebral electrodes implanted in the brain before undergoing surgery.
Of the total study population, 15 had temporal lobe epilepsy and three had extratemporal epilepsy. Eleven were affected on the left side, six on the right side, and one bi-temporally. Duration of epilepsy ranged from 8 to 40 years.
Patients listened to the Mozart piece intermittently on one day and to Haydn’s “Surprise” Symphony No. 94 the next day. Researchers counted the number of ED discharges before, during, and after the patients listened to the music.
Surprising finding
Results showed that exposure to the Mozart piece was associated with a 32% reduction in IEDs, from 28 EDs pre-exposure to 19 during exposure. However, IEDs rose to 21 post-exposure.
Overall, the Haydn piece was associated with an increase in IEDs, from 23 pre-exposure to 26 during and post-exposure.
“We saw a clear decrease in epileptic spikes while listening and after listening to Mozart, while there was an increase in spikes while listening to Haydn,” Dr. Rektor said.
He added that all 18 patients responded “more or less” to the music and that the results were statistically significant.
Dr. Rektor noted that the investigators were not surprised by the Mozart effect but were somewhat taken aback by the opposite effect from listening to Haydn.
The impact differed between men and women. The Mozart piece had a larger effect on women. In addition, the Haydn piece led to a decrease in spikes in women but led to “a clear” increase in men, Dr. Rektor reported.
In an effort to explore why the two classical pieces had such different effects, the researchers examined the acoustic properties. They worked with acoustic engineers to examine three musical properties that might influence the number of spikes: rhythm (tempo or beats per minute), dynamics (energy), and timbre (how harsh or unpleasant, how noisy, and how many “high-frequency” parts the music has).
“We observed that K448 [Mozart’s piece] has a more harmonic spectrum and its spectral content doesn’t change quickly, which probably has a positive effect on epilepsy patients,” said Dr. Rektor.
Specific features of the music had a slightly different effect on men and women. Men were more sensitive to dissonance and high-frequency parts while women were more sensitive to energy.
A new theory
Researchers previously hypothesized that the Mozart effect in epilepsy was connected to the emotional impact of music. The neurotransmitter dopamine, which plays a role in the brain’s reward system, is released when listening to music. However, the new research seems to challenge that theory. The majority of the participants did not express a strong preference for classical music.
“We believe emotions didn’t play an important role in these patients,” Dr. Rektor said, adding that the impact was instead mostly related to acoustic signals.
The team also found that the reduction in IEDs was larger in the lateral temporal lobe, the part of the brain involved in translating acoustic signals, rather than in the mesiotemporal limbic region, which plays an important role in the emotional response to music.
Comparing men with women, there’s an “overlap” of brain activation in most brain areas. However, some areas are more activated in men and others in women, said Dr. Rektor.
While the Mozart Sonata for two pianos in D Major has become the “gold standard” in this type of research, Dr. Rektor said “it’s very probable” that other classical compositions with similar acoustic properties have the same effect in epilepsy.
The investigators are testing other musical pieces, both classical and nonclassical. The ultimate aim is to develop individualized musical patterns based on these acoustic features.
“If it works, we would like to use it as a noninvasive neurostimulation method,” Dr. Rektor said.
‘Inspiring research’
Commenting on the study, session chair Marte Bjørk, MD, PhD, associate professor, department of clinical medicine, University of Bergen, Norway, called it “inspiring.” She noted that she recently had a patient whose temporal lobe seizures were consistently triggered by music played on a children’s TV program. “So I have no doubt that music can be important for some patients,” Dr. Bjørk said.
She questioned whether factors other than gender may predict response to music.
The study authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
– and now researchers believe they know why.
Investigators conducting new research found that the acoustic characteristics of Mozart’s Sonata for Two Pianos in D Major (K448) suppresses brain activity in patients with epilepsy, while a piece by the 18th century classical composer Franz Joseph Haydn did not have this effect.
Listening to this Mozart sonata and perhaps other musical pieces may eventually become a treatment for preventing epileptic seizures, said study investigator Ivan Rektor, MD, CSc, Epilepsy Centre at the Hospital St. Anne and professor at the Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
“This research into the impact of listening to music could lead to the development of a music-related type of palliative neurostimulation therapy,” said Dr. Rektor.
The findings were presented at the 2021 Congress of the European Academy of Neurology and published online in the European Journal of Neurology.
Clinically controversial?
Epilepsy affects 6 million people in Europe. Furthermore, estimates show that about 15 million Europeans have had at least one seizure at some time in their lives. In addition, about 30% of patients with epilepsy are not adequately treated with antiseizure medications.
Researchers have been studying the impact of Mozart’s music on brain-wave activity since the 1990s. Various studies report a reduction in epileptiform discharges in patients with epileptic seizures, coma, and refractory nonconvulsive status.
A 2012 meta-analysis of 12 publications involving patients with epilepsy showed an overall reduction in the number of interictal epileptic discharges (IEDs) or abnormal electrical brain waves in 84% of participants who listened to Mozart’s music. A more recent meta-analysis also showed a significant reduction in epileptic seizures and IEDs.
American researchers also found Mozart’s music regulated abnormal interictal epileptiform activity (IEA), especially in those with a high baseline rate of interictal spikes.
However, the methodological quality of some of this research “has been limited,” Dr. Rektor noted. He added that use of music therapy in clinical practice is still considered “controversial.”
The new study included 18 treatment-resistant patients with epilepsy (50% men) who ranged in age from 19 to 55 years. Participants had intracerebral electrodes implanted in the brain before undergoing surgery.
Of the total study population, 15 had temporal lobe epilepsy and three had extratemporal epilepsy. Eleven were affected on the left side, six on the right side, and one bi-temporally. Duration of epilepsy ranged from 8 to 40 years.
Patients listened to the Mozart piece intermittently on one day and to Haydn’s “Surprise” Symphony No. 94 the next day. Researchers counted the number of ED discharges before, during, and after the patients listened to the music.
Surprising finding
Results showed that exposure to the Mozart piece was associated with a 32% reduction in IEDs, from 28 EDs pre-exposure to 19 during exposure. However, IEDs rose to 21 post-exposure.
Overall, the Haydn piece was associated with an increase in IEDs, from 23 pre-exposure to 26 during and post-exposure.
“We saw a clear decrease in epileptic spikes while listening and after listening to Mozart, while there was an increase in spikes while listening to Haydn,” Dr. Rektor said.
He added that all 18 patients responded “more or less” to the music and that the results were statistically significant.
Dr. Rektor noted that the investigators were not surprised by the Mozart effect but were somewhat taken aback by the opposite effect from listening to Haydn.
The impact differed between men and women. The Mozart piece had a larger effect on women. In addition, the Haydn piece led to a decrease in spikes in women but led to “a clear” increase in men, Dr. Rektor reported.
In an effort to explore why the two classical pieces had such different effects, the researchers examined the acoustic properties. They worked with acoustic engineers to examine three musical properties that might influence the number of spikes: rhythm (tempo or beats per minute), dynamics (energy), and timbre (how harsh or unpleasant, how noisy, and how many “high-frequency” parts the music has).
“We observed that K448 [Mozart’s piece] has a more harmonic spectrum and its spectral content doesn’t change quickly, which probably has a positive effect on epilepsy patients,” said Dr. Rektor.
Specific features of the music had a slightly different effect on men and women. Men were more sensitive to dissonance and high-frequency parts while women were more sensitive to energy.
A new theory
Researchers previously hypothesized that the Mozart effect in epilepsy was connected to the emotional impact of music. The neurotransmitter dopamine, which plays a role in the brain’s reward system, is released when listening to music. However, the new research seems to challenge that theory. The majority of the participants did not express a strong preference for classical music.
“We believe emotions didn’t play an important role in these patients,” Dr. Rektor said, adding that the impact was instead mostly related to acoustic signals.
The team also found that the reduction in IEDs was larger in the lateral temporal lobe, the part of the brain involved in translating acoustic signals, rather than in the mesiotemporal limbic region, which plays an important role in the emotional response to music.
Comparing men with women, there’s an “overlap” of brain activation in most brain areas. However, some areas are more activated in men and others in women, said Dr. Rektor.
While the Mozart Sonata for two pianos in D Major has become the “gold standard” in this type of research, Dr. Rektor said “it’s very probable” that other classical compositions with similar acoustic properties have the same effect in epilepsy.
The investigators are testing other musical pieces, both classical and nonclassical. The ultimate aim is to develop individualized musical patterns based on these acoustic features.
“If it works, we would like to use it as a noninvasive neurostimulation method,” Dr. Rektor said.
‘Inspiring research’
Commenting on the study, session chair Marte Bjørk, MD, PhD, associate professor, department of clinical medicine, University of Bergen, Norway, called it “inspiring.” She noted that she recently had a patient whose temporal lobe seizures were consistently triggered by music played on a children’s TV program. “So I have no doubt that music can be important for some patients,” Dr. Bjørk said.
She questioned whether factors other than gender may predict response to music.
The study authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM EAN 2021