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Statins tied to lower risk for parkinsonism
, new research suggests. An observational study showed older adults taking statins had a lower risk for parkinsonism than their counterparts not taking statins – an effect that may be partially mediated by less severe intracranial atherosclerosis in statin users.
“These findings further support the idea that cerebrovascular disease pathologies accumulating in older brains may be an unrecognized contributor to the common occurrence of parkinsonism in old age,” the investigators wrote. “More importantly, these findings suggest that statins may have a potential therapeutic role in decreasing the magnitude of parkinsonism in older adults,” they added.
The study was published online in Neurology.
No clinical recommendations ... yet
The findings are based on 2,841 older adults enrolled in one of three ongoing clinical pathological studies at Rush Alzheimer’s Disease Center, Chicago.
Participants’ average age at baseline was 76 years, and 75% were women. None had parkinsonism at the start of the study. One-third of participants (n = 936) were taking statins. During an average follow-up of 6 years, 1,432 (50%) participants developed parkinsonism.
After controlling for demographics, vascular risk factors, and diseases, use of a statin at baseline was associated with a 16% lower risk for parkinsonism (hazard ratio, 0.84; 95% confidence interval, 0.74-0.96; P = .008). Compared with low-intensity statin therapy, moderate- or high-intensity statin therapy was associated with a 7% lower risk for parkinsonism (HR, 0.93; 95% CI, 0.87-1.00; P = .043).
The researchers also examined the brains of 1,044 people who died during the study at a mean age of 89 years. They found statin use prior to death was associated with a 37% lower odds of cerebral atherosclerosis, compared with no statin use prior to death (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001).
In a mediation analysis, both a direct (OR, 0.73; 95% CI, 0.54-0.93; P = .008) and an indirect (OR, 0.92; 95% CI, 0.88-0.97; P = .002) pathway via less severe cerebrovascular disease linked statins to parkinsonism, indicating that cerebral atherosclerosis mediated 17% of the association between statins and parkinsonism.
In line with other studies, there was no association between statins and other neurodegenerative pathologies, including Parkinson’s disease pathology. However, even older adults with a clinical diagnosis of Parkinson’s disease often show mixed brain pathologies, including cerebrovascular disease pathologies.
“Therefore, we think that statins may be beneficial against parkinsonism in patients with Parkinson’s disease, dependent on how much cerebrovascular disease pathologies they have, including atherosclerosis,” said study investigator Shahram Oveisgharan, MD, with Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago.
However, since the results stem from an observational study, “we do not yet recommend using statins in large scale for older adults at risk for parkinsonism,” Dr. Oveisgharan said.
A mixed picture
Reached for comment, Shaheen Lakhan, MD, neurologist in Newton, Massachusetts, noted that since statins were first discovered in the fermented broth of a common soil fungus in the late 1970s, they have proven to reduce cholesterol, heart disease, and stroke.
“The jury is out, however, on [their] effects on diseases such as dementia, autoimmune/inflammatory conditions, bacterial/viral infections, cancer, and parkinsonism,” he said.
“Also, the question often remains whether any benefit gained from statins is from cholesterol-lowering or through another mechanism. When there is such a mixed picture, it generally means that the drug has an effect, but not for everyone,” Dr. Lakhan said. “Much work must now be done to stratify for which patients are statins effective, ineffective, or even harmful in these conditions,” he added.
The study was supported by the National Institutes of Health. Dr. Oveisgharan and Dr. Lakhan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. An observational study showed older adults taking statins had a lower risk for parkinsonism than their counterparts not taking statins – an effect that may be partially mediated by less severe intracranial atherosclerosis in statin users.
“These findings further support the idea that cerebrovascular disease pathologies accumulating in older brains may be an unrecognized contributor to the common occurrence of parkinsonism in old age,” the investigators wrote. “More importantly, these findings suggest that statins may have a potential therapeutic role in decreasing the magnitude of parkinsonism in older adults,” they added.
The study was published online in Neurology.
No clinical recommendations ... yet
The findings are based on 2,841 older adults enrolled in one of three ongoing clinical pathological studies at Rush Alzheimer’s Disease Center, Chicago.
Participants’ average age at baseline was 76 years, and 75% were women. None had parkinsonism at the start of the study. One-third of participants (n = 936) were taking statins. During an average follow-up of 6 years, 1,432 (50%) participants developed parkinsonism.
After controlling for demographics, vascular risk factors, and diseases, use of a statin at baseline was associated with a 16% lower risk for parkinsonism (hazard ratio, 0.84; 95% confidence interval, 0.74-0.96; P = .008). Compared with low-intensity statin therapy, moderate- or high-intensity statin therapy was associated with a 7% lower risk for parkinsonism (HR, 0.93; 95% CI, 0.87-1.00; P = .043).
The researchers also examined the brains of 1,044 people who died during the study at a mean age of 89 years. They found statin use prior to death was associated with a 37% lower odds of cerebral atherosclerosis, compared with no statin use prior to death (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001).
In a mediation analysis, both a direct (OR, 0.73; 95% CI, 0.54-0.93; P = .008) and an indirect (OR, 0.92; 95% CI, 0.88-0.97; P = .002) pathway via less severe cerebrovascular disease linked statins to parkinsonism, indicating that cerebral atherosclerosis mediated 17% of the association between statins and parkinsonism.
In line with other studies, there was no association between statins and other neurodegenerative pathologies, including Parkinson’s disease pathology. However, even older adults with a clinical diagnosis of Parkinson’s disease often show mixed brain pathologies, including cerebrovascular disease pathologies.
“Therefore, we think that statins may be beneficial against parkinsonism in patients with Parkinson’s disease, dependent on how much cerebrovascular disease pathologies they have, including atherosclerosis,” said study investigator Shahram Oveisgharan, MD, with Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago.
However, since the results stem from an observational study, “we do not yet recommend using statins in large scale for older adults at risk for parkinsonism,” Dr. Oveisgharan said.
A mixed picture
Reached for comment, Shaheen Lakhan, MD, neurologist in Newton, Massachusetts, noted that since statins were first discovered in the fermented broth of a common soil fungus in the late 1970s, they have proven to reduce cholesterol, heart disease, and stroke.
“The jury is out, however, on [their] effects on diseases such as dementia, autoimmune/inflammatory conditions, bacterial/viral infections, cancer, and parkinsonism,” he said.
“Also, the question often remains whether any benefit gained from statins is from cholesterol-lowering or through another mechanism. When there is such a mixed picture, it generally means that the drug has an effect, but not for everyone,” Dr. Lakhan said. “Much work must now be done to stratify for which patients are statins effective, ineffective, or even harmful in these conditions,” he added.
The study was supported by the National Institutes of Health. Dr. Oveisgharan and Dr. Lakhan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. An observational study showed older adults taking statins had a lower risk for parkinsonism than their counterparts not taking statins – an effect that may be partially mediated by less severe intracranial atherosclerosis in statin users.
“These findings further support the idea that cerebrovascular disease pathologies accumulating in older brains may be an unrecognized contributor to the common occurrence of parkinsonism in old age,” the investigators wrote. “More importantly, these findings suggest that statins may have a potential therapeutic role in decreasing the magnitude of parkinsonism in older adults,” they added.
The study was published online in Neurology.
No clinical recommendations ... yet
The findings are based on 2,841 older adults enrolled in one of three ongoing clinical pathological studies at Rush Alzheimer’s Disease Center, Chicago.
Participants’ average age at baseline was 76 years, and 75% were women. None had parkinsonism at the start of the study. One-third of participants (n = 936) were taking statins. During an average follow-up of 6 years, 1,432 (50%) participants developed parkinsonism.
After controlling for demographics, vascular risk factors, and diseases, use of a statin at baseline was associated with a 16% lower risk for parkinsonism (hazard ratio, 0.84; 95% confidence interval, 0.74-0.96; P = .008). Compared with low-intensity statin therapy, moderate- or high-intensity statin therapy was associated with a 7% lower risk for parkinsonism (HR, 0.93; 95% CI, 0.87-1.00; P = .043).
The researchers also examined the brains of 1,044 people who died during the study at a mean age of 89 years. They found statin use prior to death was associated with a 37% lower odds of cerebral atherosclerosis, compared with no statin use prior to death (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001).
In a mediation analysis, both a direct (OR, 0.73; 95% CI, 0.54-0.93; P = .008) and an indirect (OR, 0.92; 95% CI, 0.88-0.97; P = .002) pathway via less severe cerebrovascular disease linked statins to parkinsonism, indicating that cerebral atherosclerosis mediated 17% of the association between statins and parkinsonism.
In line with other studies, there was no association between statins and other neurodegenerative pathologies, including Parkinson’s disease pathology. However, even older adults with a clinical diagnosis of Parkinson’s disease often show mixed brain pathologies, including cerebrovascular disease pathologies.
“Therefore, we think that statins may be beneficial against parkinsonism in patients with Parkinson’s disease, dependent on how much cerebrovascular disease pathologies they have, including atherosclerosis,” said study investigator Shahram Oveisgharan, MD, with Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago.
However, since the results stem from an observational study, “we do not yet recommend using statins in large scale for older adults at risk for parkinsonism,” Dr. Oveisgharan said.
A mixed picture
Reached for comment, Shaheen Lakhan, MD, neurologist in Newton, Massachusetts, noted that since statins were first discovered in the fermented broth of a common soil fungus in the late 1970s, they have proven to reduce cholesterol, heart disease, and stroke.
“The jury is out, however, on [their] effects on diseases such as dementia, autoimmune/inflammatory conditions, bacterial/viral infections, cancer, and parkinsonism,” he said.
“Also, the question often remains whether any benefit gained from statins is from cholesterol-lowering or through another mechanism. When there is such a mixed picture, it generally means that the drug has an effect, but not for everyone,” Dr. Lakhan said. “Much work must now be done to stratify for which patients are statins effective, ineffective, or even harmful in these conditions,” he added.
The study was supported by the National Institutes of Health. Dr. Oveisgharan and Dr. Lakhan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Novel combo drug shows promise as first-line Parkinson’s disease treatment
, new research suggests. Results from a phase 3 trial of P2B001, a combination of pramipexole and rasagiline at currently unavailable low doses, showed the drug was more effective than its individual components and as effective as higher-dose pramipexole ER – with far less daytime sleepiness.
The combination drug is taken once per day and does not require titration, which investigators say make it a good option for first-line treatment of Parkinson’s disease.
“I don’t think people, including me, expected intuitively that if you used small doses and combined it with a little rasagiline it would be equal to full doses of pramipexole, but it appears that it is,” said lead investigator Warren Olanow, MD, professor and chair emeritus of neurology and professor emeritus of neuroscience at Icahn School of Medicine at Mount Sinai, New York.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
‘Synergistic effects’
Levodopa is considered to be the most effective treatment for Parkinson’s disease, but long-term use is associated with increased risk for motor complications, such as dyskinesia. Dopamine agonists such as pramipexole have been linked in previous research to excessive daytime sleepiness and impulse control disorders. In addition, monoamine oxidase-B inhibitors such as rasagiline are not as effective at controlling Parkinson’s disease as other treatment options.
“There is no consistent agreement on how to initiate treatment because no one treatment is ideal,” Dr. Olanow said.
P2B001, developed by Pharma Two B, is a combination of 0.6 mg of pramipexole and 0.75 mg of rasagiline. The drugs work by dual mechanisms, which investigators suspected might have “synergistic effects.”
Following promising results from an earlier trial, researches launched a phase 3, 12-week, international, randomized, double-blind trial to study the efficacy, safety, and tolerability of P2B001, compared with its individual components and with a calibration arm of pramipexole ER in 519 patients with early Parkinson’s disease.
Participants received P2B001, 0.6 mg of pramipexole ER, 0.75 mg of rasagiline ER, or pramipexole ER titrated to an optimal dose for each patient (1.5-4.5 mg).
New first-line treatment?
Results showed that the adjusted mean change from baseline in total Unified Parkinson’s Disease Rating Scale (UPDRS) score was -2.66 points for P2B001 versus pramipexole (P = .0018) and -3.30 points for P2B001 versus rasagiline (P = .0001).
There was no significant difference in UPDRS scores between P2B001 and pramipexole ER, but patients who received P2B001 reported significantly less daytime sleepiness.
The adjusted mean change from baseline in Epworth Sleepiness Scale score for P2B001 versus pramipexole ER was -2.66 points (P < .0001).
In addition, fewer dopaminergic adverse events were reported with the combination drug versus pramipexole ER (44.7% vs. 66.2%), including somnolence (14.7% vs. 31.1%) and orthostatic hypotension (2.7% vs. 12.2%).
As a first-line treatment, P2B001 could offer an effective option instead of levodopa, Dr. Olanow said. “It could be really good for patients because it would delay the introduction of levodopa and allow levodopa to be used in lower doses when the time comes and hopefully reduce the risk of complications,” he added.
Questions, cost concerns
Commenting on the study, Alfonso Fasano, MD, PhD, professor of neurology and chair in neuromodulation, University of Toronto, agreed that better therapeutic options are needed for Parkinson’s disease.
Combining available treatments into one pill “might help patients’ adherence, although this can compromise our ability to dose each compound individually,” said Dr. Fasano, who was not involved with the research.
He added that there are also questions about dosage modification as a patient’s disease progresses and whether a higher dose might pose safety problems. There is also the issue of cost. “Conducting large clinical trials like this one is expensive, and I wonder about the cost of the drug when approved,” Dr. Fasano noted. “Do we really need to invest in combination pills containing two already well-known compounds?”
Dr. Olanow, who is not directly involved with Pharma Two B, the developer of P2B001, said he has no information on what the drug might cost or how it might be marketed if approved for use.
“The advantage of the combination is the component doses are not replicable, they are both in an extended-release formulation, it doesn’t require titration, and it has been tested and proven to work,” he said.
The study was funded by Pharma Two B. Dr. Olanow is employed by Clintrex Research Corporation and owns stock in Clintrex Research Corporation. Dr. Fasano reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. Results from a phase 3 trial of P2B001, a combination of pramipexole and rasagiline at currently unavailable low doses, showed the drug was more effective than its individual components and as effective as higher-dose pramipexole ER – with far less daytime sleepiness.
The combination drug is taken once per day and does not require titration, which investigators say make it a good option for first-line treatment of Parkinson’s disease.
“I don’t think people, including me, expected intuitively that if you used small doses and combined it with a little rasagiline it would be equal to full doses of pramipexole, but it appears that it is,” said lead investigator Warren Olanow, MD, professor and chair emeritus of neurology and professor emeritus of neuroscience at Icahn School of Medicine at Mount Sinai, New York.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
‘Synergistic effects’
Levodopa is considered to be the most effective treatment for Parkinson’s disease, but long-term use is associated with increased risk for motor complications, such as dyskinesia. Dopamine agonists such as pramipexole have been linked in previous research to excessive daytime sleepiness and impulse control disorders. In addition, monoamine oxidase-B inhibitors such as rasagiline are not as effective at controlling Parkinson’s disease as other treatment options.
“There is no consistent agreement on how to initiate treatment because no one treatment is ideal,” Dr. Olanow said.
P2B001, developed by Pharma Two B, is a combination of 0.6 mg of pramipexole and 0.75 mg of rasagiline. The drugs work by dual mechanisms, which investigators suspected might have “synergistic effects.”
Following promising results from an earlier trial, researches launched a phase 3, 12-week, international, randomized, double-blind trial to study the efficacy, safety, and tolerability of P2B001, compared with its individual components and with a calibration arm of pramipexole ER in 519 patients with early Parkinson’s disease.
Participants received P2B001, 0.6 mg of pramipexole ER, 0.75 mg of rasagiline ER, or pramipexole ER titrated to an optimal dose for each patient (1.5-4.5 mg).
New first-line treatment?
Results showed that the adjusted mean change from baseline in total Unified Parkinson’s Disease Rating Scale (UPDRS) score was -2.66 points for P2B001 versus pramipexole (P = .0018) and -3.30 points for P2B001 versus rasagiline (P = .0001).
There was no significant difference in UPDRS scores between P2B001 and pramipexole ER, but patients who received P2B001 reported significantly less daytime sleepiness.
The adjusted mean change from baseline in Epworth Sleepiness Scale score for P2B001 versus pramipexole ER was -2.66 points (P < .0001).
In addition, fewer dopaminergic adverse events were reported with the combination drug versus pramipexole ER (44.7% vs. 66.2%), including somnolence (14.7% vs. 31.1%) and orthostatic hypotension (2.7% vs. 12.2%).
As a first-line treatment, P2B001 could offer an effective option instead of levodopa, Dr. Olanow said. “It could be really good for patients because it would delay the introduction of levodopa and allow levodopa to be used in lower doses when the time comes and hopefully reduce the risk of complications,” he added.
Questions, cost concerns
Commenting on the study, Alfonso Fasano, MD, PhD, professor of neurology and chair in neuromodulation, University of Toronto, agreed that better therapeutic options are needed for Parkinson’s disease.
Combining available treatments into one pill “might help patients’ adherence, although this can compromise our ability to dose each compound individually,” said Dr. Fasano, who was not involved with the research.
He added that there are also questions about dosage modification as a patient’s disease progresses and whether a higher dose might pose safety problems. There is also the issue of cost. “Conducting large clinical trials like this one is expensive, and I wonder about the cost of the drug when approved,” Dr. Fasano noted. “Do we really need to invest in combination pills containing two already well-known compounds?”
Dr. Olanow, who is not directly involved with Pharma Two B, the developer of P2B001, said he has no information on what the drug might cost or how it might be marketed if approved for use.
“The advantage of the combination is the component doses are not replicable, they are both in an extended-release formulation, it doesn’t require titration, and it has been tested and proven to work,” he said.
The study was funded by Pharma Two B. Dr. Olanow is employed by Clintrex Research Corporation and owns stock in Clintrex Research Corporation. Dr. Fasano reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. Results from a phase 3 trial of P2B001, a combination of pramipexole and rasagiline at currently unavailable low doses, showed the drug was more effective than its individual components and as effective as higher-dose pramipexole ER – with far less daytime sleepiness.
The combination drug is taken once per day and does not require titration, which investigators say make it a good option for first-line treatment of Parkinson’s disease.
“I don’t think people, including me, expected intuitively that if you used small doses and combined it with a little rasagiline it would be equal to full doses of pramipexole, but it appears that it is,” said lead investigator Warren Olanow, MD, professor and chair emeritus of neurology and professor emeritus of neuroscience at Icahn School of Medicine at Mount Sinai, New York.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
‘Synergistic effects’
Levodopa is considered to be the most effective treatment for Parkinson’s disease, but long-term use is associated with increased risk for motor complications, such as dyskinesia. Dopamine agonists such as pramipexole have been linked in previous research to excessive daytime sleepiness and impulse control disorders. In addition, monoamine oxidase-B inhibitors such as rasagiline are not as effective at controlling Parkinson’s disease as other treatment options.
“There is no consistent agreement on how to initiate treatment because no one treatment is ideal,” Dr. Olanow said.
P2B001, developed by Pharma Two B, is a combination of 0.6 mg of pramipexole and 0.75 mg of rasagiline. The drugs work by dual mechanisms, which investigators suspected might have “synergistic effects.”
Following promising results from an earlier trial, researches launched a phase 3, 12-week, international, randomized, double-blind trial to study the efficacy, safety, and tolerability of P2B001, compared with its individual components and with a calibration arm of pramipexole ER in 519 patients with early Parkinson’s disease.
Participants received P2B001, 0.6 mg of pramipexole ER, 0.75 mg of rasagiline ER, or pramipexole ER titrated to an optimal dose for each patient (1.5-4.5 mg).
New first-line treatment?
Results showed that the adjusted mean change from baseline in total Unified Parkinson’s Disease Rating Scale (UPDRS) score was -2.66 points for P2B001 versus pramipexole (P = .0018) and -3.30 points for P2B001 versus rasagiline (P = .0001).
There was no significant difference in UPDRS scores between P2B001 and pramipexole ER, but patients who received P2B001 reported significantly less daytime sleepiness.
The adjusted mean change from baseline in Epworth Sleepiness Scale score for P2B001 versus pramipexole ER was -2.66 points (P < .0001).
In addition, fewer dopaminergic adverse events were reported with the combination drug versus pramipexole ER (44.7% vs. 66.2%), including somnolence (14.7% vs. 31.1%) and orthostatic hypotension (2.7% vs. 12.2%).
As a first-line treatment, P2B001 could offer an effective option instead of levodopa, Dr. Olanow said. “It could be really good for patients because it would delay the introduction of levodopa and allow levodopa to be used in lower doses when the time comes and hopefully reduce the risk of complications,” he added.
Questions, cost concerns
Commenting on the study, Alfonso Fasano, MD, PhD, professor of neurology and chair in neuromodulation, University of Toronto, agreed that better therapeutic options are needed for Parkinson’s disease.
Combining available treatments into one pill “might help patients’ adherence, although this can compromise our ability to dose each compound individually,” said Dr. Fasano, who was not involved with the research.
He added that there are also questions about dosage modification as a patient’s disease progresses and whether a higher dose might pose safety problems. There is also the issue of cost. “Conducting large clinical trials like this one is expensive, and I wonder about the cost of the drug when approved,” Dr. Fasano noted. “Do we really need to invest in combination pills containing two already well-known compounds?”
Dr. Olanow, who is not directly involved with Pharma Two B, the developer of P2B001, said he has no information on what the drug might cost or how it might be marketed if approved for use.
“The advantage of the combination is the component doses are not replicable, they are both in an extended-release formulation, it doesn’t require titration, and it has been tested and proven to work,” he said.
The study was funded by Pharma Two B. Dr. Olanow is employed by Clintrex Research Corporation and owns stock in Clintrex Research Corporation. Dr. Fasano reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAN 2022
Atypical anxiety offers intervention target in Parkinson’s disease
Anxiety is common in Parkinson’s disease (PD) and has been shown to increase functional disability and decrease quality of life, but atypical presentations of anxiety are underrecognized and often undertreated in PD patients, wrote Nadeeka N. Dissanayaka, PhD, of the University of Queensland, Brisbane, Australia, and colleagues.
In a study published in the American Journal of Geriatric Psychiatry , the researchers conducted a systematic review of 60 studies to better characterize atypical PD-related anxiety. Fourteen studies involved Anxiety Not Otherwise Specified (NOS), 31 included fluctuating anxiety symptoms, and 22 included Fear of Falling (FOF).
Overall, the average prevalence rate for anxiety disorders in the PD population was 31%.
Anxiety NOS, fluctuating anxiety, and FOF accounted for a weighted mean prevalence of 14.9%, 34.19%, and 51.5%, respectively.
The symptomatology of anxiety NOS included psychological distress about the PD diagnosis, insecurity about the future, fear of losing control of motor and bodily functions, and social embarrassment. Clinically, anxiety NOS was associated with a range of factors including minor depression, on-off motor symptoms, muscle cramps, poor quality of life, and gait impairment.
The symptomatology of fluctuating anxiety was assessed in 9 studies of the “on” motor state and 16 studies of both “on” and “off.” Symptoms associated with the off state included panic attacks, feeling anxious or sad, and avoiding situations, as well as palpitations, dizziness, chills, and hot flashes.
Clinically, studies showed that anxiety was more severe in the off-medication state, and symptoms were reduced in the on state. Data from some studies showed that fluctuating anxiety was more common in PD patients who were female, and who had a younger age of PD onset and longer disease duration.
The symptomatology of FOF included associations between FOF and difficulty with walking and gait: Using a walker or other device, more frequent freezing in place, hesitation when turning, and slower speed while walking. Clinically, characteristics associated with FOF included older age, needing assistance for activities of daily living, a history of falls, and reduced quality of life.
The results of the review were limited by several factors including the varying assessment techniques, and the lack of data on treatment for atypical anxiety in PD, the researchers noted. “To our knowledge there are no treatment trials focused on Anxiety NOS,” and studies on the treatment of fluctuating anxiety and FOF are preliminary, they said.
However, the results support the need for early identification and classification of PD-related anxiety to improve treatment strategies and long-term outcomes, the researchers concluded. In the absence of evidence-based treatment strategies, “Given the heterogeneity of anxiety presentations in PD, the importance of tailoring interventions to meet the specific needs and unique symptom profiles of each individual cannot be overstated,” and routine screening of PD patients for anxiety every 6-12 months is recommended, they emphasized.
Dr. Dissanayaka disclosed support from the National Health and Medical Research Boosting Dementia Research Leadership Fellowship.
Anxiety is common in Parkinson’s disease (PD) and has been shown to increase functional disability and decrease quality of life, but atypical presentations of anxiety are underrecognized and often undertreated in PD patients, wrote Nadeeka N. Dissanayaka, PhD, of the University of Queensland, Brisbane, Australia, and colleagues.
In a study published in the American Journal of Geriatric Psychiatry , the researchers conducted a systematic review of 60 studies to better characterize atypical PD-related anxiety. Fourteen studies involved Anxiety Not Otherwise Specified (NOS), 31 included fluctuating anxiety symptoms, and 22 included Fear of Falling (FOF).
Overall, the average prevalence rate for anxiety disorders in the PD population was 31%.
Anxiety NOS, fluctuating anxiety, and FOF accounted for a weighted mean prevalence of 14.9%, 34.19%, and 51.5%, respectively.
The symptomatology of anxiety NOS included psychological distress about the PD diagnosis, insecurity about the future, fear of losing control of motor and bodily functions, and social embarrassment. Clinically, anxiety NOS was associated with a range of factors including minor depression, on-off motor symptoms, muscle cramps, poor quality of life, and gait impairment.
The symptomatology of fluctuating anxiety was assessed in 9 studies of the “on” motor state and 16 studies of both “on” and “off.” Symptoms associated with the off state included panic attacks, feeling anxious or sad, and avoiding situations, as well as palpitations, dizziness, chills, and hot flashes.
Clinically, studies showed that anxiety was more severe in the off-medication state, and symptoms were reduced in the on state. Data from some studies showed that fluctuating anxiety was more common in PD patients who were female, and who had a younger age of PD onset and longer disease duration.
The symptomatology of FOF included associations between FOF and difficulty with walking and gait: Using a walker or other device, more frequent freezing in place, hesitation when turning, and slower speed while walking. Clinically, characteristics associated with FOF included older age, needing assistance for activities of daily living, a history of falls, and reduced quality of life.
The results of the review were limited by several factors including the varying assessment techniques, and the lack of data on treatment for atypical anxiety in PD, the researchers noted. “To our knowledge there are no treatment trials focused on Anxiety NOS,” and studies on the treatment of fluctuating anxiety and FOF are preliminary, they said.
However, the results support the need for early identification and classification of PD-related anxiety to improve treatment strategies and long-term outcomes, the researchers concluded. In the absence of evidence-based treatment strategies, “Given the heterogeneity of anxiety presentations in PD, the importance of tailoring interventions to meet the specific needs and unique symptom profiles of each individual cannot be overstated,” and routine screening of PD patients for anxiety every 6-12 months is recommended, they emphasized.
Dr. Dissanayaka disclosed support from the National Health and Medical Research Boosting Dementia Research Leadership Fellowship.
Anxiety is common in Parkinson’s disease (PD) and has been shown to increase functional disability and decrease quality of life, but atypical presentations of anxiety are underrecognized and often undertreated in PD patients, wrote Nadeeka N. Dissanayaka, PhD, of the University of Queensland, Brisbane, Australia, and colleagues.
In a study published in the American Journal of Geriatric Psychiatry , the researchers conducted a systematic review of 60 studies to better characterize atypical PD-related anxiety. Fourteen studies involved Anxiety Not Otherwise Specified (NOS), 31 included fluctuating anxiety symptoms, and 22 included Fear of Falling (FOF).
Overall, the average prevalence rate for anxiety disorders in the PD population was 31%.
Anxiety NOS, fluctuating anxiety, and FOF accounted for a weighted mean prevalence of 14.9%, 34.19%, and 51.5%, respectively.
The symptomatology of anxiety NOS included psychological distress about the PD diagnosis, insecurity about the future, fear of losing control of motor and bodily functions, and social embarrassment. Clinically, anxiety NOS was associated with a range of factors including minor depression, on-off motor symptoms, muscle cramps, poor quality of life, and gait impairment.
The symptomatology of fluctuating anxiety was assessed in 9 studies of the “on” motor state and 16 studies of both “on” and “off.” Symptoms associated with the off state included panic attacks, feeling anxious or sad, and avoiding situations, as well as palpitations, dizziness, chills, and hot flashes.
Clinically, studies showed that anxiety was more severe in the off-medication state, and symptoms were reduced in the on state. Data from some studies showed that fluctuating anxiety was more common in PD patients who were female, and who had a younger age of PD onset and longer disease duration.
The symptomatology of FOF included associations between FOF and difficulty with walking and gait: Using a walker or other device, more frequent freezing in place, hesitation when turning, and slower speed while walking. Clinically, characteristics associated with FOF included older age, needing assistance for activities of daily living, a history of falls, and reduced quality of life.
The results of the review were limited by several factors including the varying assessment techniques, and the lack of data on treatment for atypical anxiety in PD, the researchers noted. “To our knowledge there are no treatment trials focused on Anxiety NOS,” and studies on the treatment of fluctuating anxiety and FOF are preliminary, they said.
However, the results support the need for early identification and classification of PD-related anxiety to improve treatment strategies and long-term outcomes, the researchers concluded. In the absence of evidence-based treatment strategies, “Given the heterogeneity of anxiety presentations in PD, the importance of tailoring interventions to meet the specific needs and unique symptom profiles of each individual cannot be overstated,” and routine screening of PD patients for anxiety every 6-12 months is recommended, they emphasized.
Dr. Dissanayaka disclosed support from the National Health and Medical Research Boosting Dementia Research Leadership Fellowship.
FROM THE AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
New guidance on palliative care for neurologic disorders
Palliative care includes much more than hospice services, lead author of the new position statement Lynne P. Taylor, MD, University of Washington, Seattle, and a fellow of the AAN, said in a press release.
“Neurologists provide palliative care to people living with life-altering neurologic illnesses not just at the end of life but throughout the course of a disease, improving their lives with symptom control,” Dr. Taylor added.
The position paper, developed by a joint committee of the AAN, American Neurological Association, and Child Neurology Society, was published online March 8 in Neurology.
Guidance across the lifespan
The new paper, an update of previous position statements, includes palliative care guidance for different neurologic disorders across the lifespan. For example, neuropalliative care for neonates deserves “extra consideration,” because one-third of pediatric deaths occur during the neonatal period, most often in the neonatal intensive care unit, and after withdrawal of life-sustaining interventions, the authors note.
For older children, neuropalliative care consultation benefits families trying to maximize the quality of the remainder of their child’s life. Decisionmaking must consider the child’s cognitive abilities, the diagnosis, the perceived level of suffering, parental values, and the family’s understanding of the prognosis, the authors note.
They note that discussions about prognosis are often difficult but critical. Previous research “supports that patients desire prognostic information even when prognosis is uncertain and appreciate when their physicians disclose the presence of that uncertainty,” the authors note.
Also important is engaging in shared decisionmaking with patients and families. “This approach requires the physician to elicit a patient’s goals, make recommendations based on whether medical treatments are likely to achieve those goals, and work with patients and families to finalize a treatment plan,” according to the new guidance.
Ethical considerations
When treatments are physiologically futile, clinicians need to explain why interventions that may cause harm and have no benefit are not offered.
The authors cite cardiopulmonary resuscitation in the setting of cardiac arrest from irreversible herniation as an example of futility in the context of neurologic disease.
When life-prolonging care is no longer an option, clinicians have an obligation to shift the focus of care to preserving quality of life and comfort as much as possible, they add.
Hospices, which provide comfort-focused medical care as well as psychosocial and spiritual support, are reserved for patients believed to be in the last 6 months of their life if their disease follows the expected course.
The investigators also broached ethical considerations for individual neurologic conditions. Concerns for disorders of consciousness include misdiagnosis or inaccurate prognostication, and serial examinations are needed to re-evaluate levels of cognition, psychological state, decisionmaking capacity, and disease trajectory.
In patients with locked-in syndrome, a state of irreversible paralysis, often with respiratory and vocal paralysis, consciousness may range from a chronic minimally conscious state to intact cognition.
Without careful examination, patients with preserved consciousness may be mistaken as having a disorder of consciousness and risk their decisional capacity being ignored, the researchers note.
These patients may need assistance from speech pathologists to identify techniques to enhance communication, such as careful “yes/no” questioning, communication boards, or advanced eye-gaze technology, they add.
Stroke, dementia, Parkinson’s guidance
For stroke, the guidance suggests neurologists encourage patients with retained decisionmaking capacity to complete advance care planning given the risk of recurrent stroke and loss of capacity in the future.
For dementia, a proper and timely diagnosis can help patients and their families prepare for the consequences of cognitive dysfunction and loss of autonomy while respecting their identified values, the authors write.
They note that for Parkinson’s disease, which is marked by slow functional and cognitive decline, neurologists must aim to anticipate and treat symptoms, address psychosocial and spiritual distress and caregiver burden, and engage patients and families in advance care planning before onset of cognitive impairment.
For patients with amyotrophic lateral sclerosis (ALS) and related disorders, clinicians should aim to document goals and treatment preferences prior to extreme weakness and aphonia.
It is also important to anticipate patient preferences for future disability-specific decisions, such as those related to feeding tubes and mechanical ventilation, and to identify the patient’s minimal acceptable outcome from these life-sustaining interventions.
On the topic of withdrawal of treatment, the paper notes that competent patients have the right to refuse life-prolonging therapies, including artificial nutrition, hydration, mechanical ventilation, and antibiotics. If physicians have a moral objection to removing life-support systems, they are obligated to transfer the care of the patient to another physician, the authors add.
Once a decision is made to forgo life-sustaining treatment, physicians should minimize subsequent suffering. The investigators note most symptoms at the end of life can be managed without sedation.
In broaching the “gap” in neurology training programs, the statement referred to a survey of 49 neurology residency programs. Results showed that 42% of respondents reported being dissatisfied with their palliative care education.
Well-timed update
Kate T. Brizzi, MD, a Boston neurologist with experience in hospice and palliative care, said the updated position statement is “well-timed” as neuropalliative care has evolved dramatically over the last decade.
“In the last several years, I’ve witnessed a significant increase in trainee interest in the field, and there is growing recognition of how a palliative care approach can improve patient care and hopefully outcomes,” said Dr. Brizzi.
She praised the authors for doing “an excellent job” in highlighting the ethical challenges facing the neurology provider, particularly as it relates to prognostication in an uncertain setting.
Dr. Brizzi noted communication tools that help facilitate discussions around shared decisionmaking “have enhanced our ability to meet the palliative care needs of our patients and can be incorporated by any provider.”
However, she added that the paper only briefly comments on the role of the neurologist in “lawful physician-hastened death.”
“I anticipate that this will be an area of further discussion in the neurology and palliative care community in the future, as requests for hastened death are frequently encountered from patients with serious neurologic illness,” she said.
Dr. Brizzi also noted the importance of understanding the reasons behind the request – and addressing patient worries related to end-of-life care, which can frequently help alleviate distress.
There was no targeted funding for this paper. Coauthor Salvador Cruz-Flores, MD, department of neurology, Texas Tech University Center, El Paso, reported participation on member adjudication committees for clinical trials for Novo Nordisk, Sunovion, and Galapagos. The remaining authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Palliative care includes much more than hospice services, lead author of the new position statement Lynne P. Taylor, MD, University of Washington, Seattle, and a fellow of the AAN, said in a press release.
“Neurologists provide palliative care to people living with life-altering neurologic illnesses not just at the end of life but throughout the course of a disease, improving their lives with symptom control,” Dr. Taylor added.
The position paper, developed by a joint committee of the AAN, American Neurological Association, and Child Neurology Society, was published online March 8 in Neurology.
Guidance across the lifespan
The new paper, an update of previous position statements, includes palliative care guidance for different neurologic disorders across the lifespan. For example, neuropalliative care for neonates deserves “extra consideration,” because one-third of pediatric deaths occur during the neonatal period, most often in the neonatal intensive care unit, and after withdrawal of life-sustaining interventions, the authors note.
For older children, neuropalliative care consultation benefits families trying to maximize the quality of the remainder of their child’s life. Decisionmaking must consider the child’s cognitive abilities, the diagnosis, the perceived level of suffering, parental values, and the family’s understanding of the prognosis, the authors note.
They note that discussions about prognosis are often difficult but critical. Previous research “supports that patients desire prognostic information even when prognosis is uncertain and appreciate when their physicians disclose the presence of that uncertainty,” the authors note.
Also important is engaging in shared decisionmaking with patients and families. “This approach requires the physician to elicit a patient’s goals, make recommendations based on whether medical treatments are likely to achieve those goals, and work with patients and families to finalize a treatment plan,” according to the new guidance.
Ethical considerations
When treatments are physiologically futile, clinicians need to explain why interventions that may cause harm and have no benefit are not offered.
The authors cite cardiopulmonary resuscitation in the setting of cardiac arrest from irreversible herniation as an example of futility in the context of neurologic disease.
When life-prolonging care is no longer an option, clinicians have an obligation to shift the focus of care to preserving quality of life and comfort as much as possible, they add.
Hospices, which provide comfort-focused medical care as well as psychosocial and spiritual support, are reserved for patients believed to be in the last 6 months of their life if their disease follows the expected course.
The investigators also broached ethical considerations for individual neurologic conditions. Concerns for disorders of consciousness include misdiagnosis or inaccurate prognostication, and serial examinations are needed to re-evaluate levels of cognition, psychological state, decisionmaking capacity, and disease trajectory.
In patients with locked-in syndrome, a state of irreversible paralysis, often with respiratory and vocal paralysis, consciousness may range from a chronic minimally conscious state to intact cognition.
Without careful examination, patients with preserved consciousness may be mistaken as having a disorder of consciousness and risk their decisional capacity being ignored, the researchers note.
These patients may need assistance from speech pathologists to identify techniques to enhance communication, such as careful “yes/no” questioning, communication boards, or advanced eye-gaze technology, they add.
Stroke, dementia, Parkinson’s guidance
For stroke, the guidance suggests neurologists encourage patients with retained decisionmaking capacity to complete advance care planning given the risk of recurrent stroke and loss of capacity in the future.
For dementia, a proper and timely diagnosis can help patients and their families prepare for the consequences of cognitive dysfunction and loss of autonomy while respecting their identified values, the authors write.
They note that for Parkinson’s disease, which is marked by slow functional and cognitive decline, neurologists must aim to anticipate and treat symptoms, address psychosocial and spiritual distress and caregiver burden, and engage patients and families in advance care planning before onset of cognitive impairment.
For patients with amyotrophic lateral sclerosis (ALS) and related disorders, clinicians should aim to document goals and treatment preferences prior to extreme weakness and aphonia.
It is also important to anticipate patient preferences for future disability-specific decisions, such as those related to feeding tubes and mechanical ventilation, and to identify the patient’s minimal acceptable outcome from these life-sustaining interventions.
On the topic of withdrawal of treatment, the paper notes that competent patients have the right to refuse life-prolonging therapies, including artificial nutrition, hydration, mechanical ventilation, and antibiotics. If physicians have a moral objection to removing life-support systems, they are obligated to transfer the care of the patient to another physician, the authors add.
Once a decision is made to forgo life-sustaining treatment, physicians should minimize subsequent suffering. The investigators note most symptoms at the end of life can be managed without sedation.
In broaching the “gap” in neurology training programs, the statement referred to a survey of 49 neurology residency programs. Results showed that 42% of respondents reported being dissatisfied with their palliative care education.
Well-timed update
Kate T. Brizzi, MD, a Boston neurologist with experience in hospice and palliative care, said the updated position statement is “well-timed” as neuropalliative care has evolved dramatically over the last decade.
“In the last several years, I’ve witnessed a significant increase in trainee interest in the field, and there is growing recognition of how a palliative care approach can improve patient care and hopefully outcomes,” said Dr. Brizzi.
She praised the authors for doing “an excellent job” in highlighting the ethical challenges facing the neurology provider, particularly as it relates to prognostication in an uncertain setting.
Dr. Brizzi noted communication tools that help facilitate discussions around shared decisionmaking “have enhanced our ability to meet the palliative care needs of our patients and can be incorporated by any provider.”
However, she added that the paper only briefly comments on the role of the neurologist in “lawful physician-hastened death.”
“I anticipate that this will be an area of further discussion in the neurology and palliative care community in the future, as requests for hastened death are frequently encountered from patients with serious neurologic illness,” she said.
Dr. Brizzi also noted the importance of understanding the reasons behind the request – and addressing patient worries related to end-of-life care, which can frequently help alleviate distress.
There was no targeted funding for this paper. Coauthor Salvador Cruz-Flores, MD, department of neurology, Texas Tech University Center, El Paso, reported participation on member adjudication committees for clinical trials for Novo Nordisk, Sunovion, and Galapagos. The remaining authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Palliative care includes much more than hospice services, lead author of the new position statement Lynne P. Taylor, MD, University of Washington, Seattle, and a fellow of the AAN, said in a press release.
“Neurologists provide palliative care to people living with life-altering neurologic illnesses not just at the end of life but throughout the course of a disease, improving their lives with symptom control,” Dr. Taylor added.
The position paper, developed by a joint committee of the AAN, American Neurological Association, and Child Neurology Society, was published online March 8 in Neurology.
Guidance across the lifespan
The new paper, an update of previous position statements, includes palliative care guidance for different neurologic disorders across the lifespan. For example, neuropalliative care for neonates deserves “extra consideration,” because one-third of pediatric deaths occur during the neonatal period, most often in the neonatal intensive care unit, and after withdrawal of life-sustaining interventions, the authors note.
For older children, neuropalliative care consultation benefits families trying to maximize the quality of the remainder of their child’s life. Decisionmaking must consider the child’s cognitive abilities, the diagnosis, the perceived level of suffering, parental values, and the family’s understanding of the prognosis, the authors note.
They note that discussions about prognosis are often difficult but critical. Previous research “supports that patients desire prognostic information even when prognosis is uncertain and appreciate when their physicians disclose the presence of that uncertainty,” the authors note.
Also important is engaging in shared decisionmaking with patients and families. “This approach requires the physician to elicit a patient’s goals, make recommendations based on whether medical treatments are likely to achieve those goals, and work with patients and families to finalize a treatment plan,” according to the new guidance.
Ethical considerations
When treatments are physiologically futile, clinicians need to explain why interventions that may cause harm and have no benefit are not offered.
The authors cite cardiopulmonary resuscitation in the setting of cardiac arrest from irreversible herniation as an example of futility in the context of neurologic disease.
When life-prolonging care is no longer an option, clinicians have an obligation to shift the focus of care to preserving quality of life and comfort as much as possible, they add.
Hospices, which provide comfort-focused medical care as well as psychosocial and spiritual support, are reserved for patients believed to be in the last 6 months of their life if their disease follows the expected course.
The investigators also broached ethical considerations for individual neurologic conditions. Concerns for disorders of consciousness include misdiagnosis or inaccurate prognostication, and serial examinations are needed to re-evaluate levels of cognition, psychological state, decisionmaking capacity, and disease trajectory.
In patients with locked-in syndrome, a state of irreversible paralysis, often with respiratory and vocal paralysis, consciousness may range from a chronic minimally conscious state to intact cognition.
Without careful examination, patients with preserved consciousness may be mistaken as having a disorder of consciousness and risk their decisional capacity being ignored, the researchers note.
These patients may need assistance from speech pathologists to identify techniques to enhance communication, such as careful “yes/no” questioning, communication boards, or advanced eye-gaze technology, they add.
Stroke, dementia, Parkinson’s guidance
For stroke, the guidance suggests neurologists encourage patients with retained decisionmaking capacity to complete advance care planning given the risk of recurrent stroke and loss of capacity in the future.
For dementia, a proper and timely diagnosis can help patients and their families prepare for the consequences of cognitive dysfunction and loss of autonomy while respecting their identified values, the authors write.
They note that for Parkinson’s disease, which is marked by slow functional and cognitive decline, neurologists must aim to anticipate and treat symptoms, address psychosocial and spiritual distress and caregiver burden, and engage patients and families in advance care planning before onset of cognitive impairment.
For patients with amyotrophic lateral sclerosis (ALS) and related disorders, clinicians should aim to document goals and treatment preferences prior to extreme weakness and aphonia.
It is also important to anticipate patient preferences for future disability-specific decisions, such as those related to feeding tubes and mechanical ventilation, and to identify the patient’s minimal acceptable outcome from these life-sustaining interventions.
On the topic of withdrawal of treatment, the paper notes that competent patients have the right to refuse life-prolonging therapies, including artificial nutrition, hydration, mechanical ventilation, and antibiotics. If physicians have a moral objection to removing life-support systems, they are obligated to transfer the care of the patient to another physician, the authors add.
Once a decision is made to forgo life-sustaining treatment, physicians should minimize subsequent suffering. The investigators note most symptoms at the end of life can be managed without sedation.
In broaching the “gap” in neurology training programs, the statement referred to a survey of 49 neurology residency programs. Results showed that 42% of respondents reported being dissatisfied with their palliative care education.
Well-timed update
Kate T. Brizzi, MD, a Boston neurologist with experience in hospice and palliative care, said the updated position statement is “well-timed” as neuropalliative care has evolved dramatically over the last decade.
“In the last several years, I’ve witnessed a significant increase in trainee interest in the field, and there is growing recognition of how a palliative care approach can improve patient care and hopefully outcomes,” said Dr. Brizzi.
She praised the authors for doing “an excellent job” in highlighting the ethical challenges facing the neurology provider, particularly as it relates to prognostication in an uncertain setting.
Dr. Brizzi noted communication tools that help facilitate discussions around shared decisionmaking “have enhanced our ability to meet the palliative care needs of our patients and can be incorporated by any provider.”
However, she added that the paper only briefly comments on the role of the neurologist in “lawful physician-hastened death.”
“I anticipate that this will be an area of further discussion in the neurology and palliative care community in the future, as requests for hastened death are frequently encountered from patients with serious neurologic illness,” she said.
Dr. Brizzi also noted the importance of understanding the reasons behind the request – and addressing patient worries related to end-of-life care, which can frequently help alleviate distress.
There was no targeted funding for this paper. Coauthor Salvador Cruz-Flores, MD, department of neurology, Texas Tech University Center, El Paso, reported participation on member adjudication committees for clinical trials for Novo Nordisk, Sunovion, and Galapagos. The remaining authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From Neurology
Tremors and memory loss precede Parkinson’s in diverse population
Tremors and memory symptoms were identified among individuals in a primary care setting as early as 10 years before a Parkinson’s disease diagnosis in a new study.
Most research on the causes and early signs of Parkinson’s disease (PD) have involved patients of Northern European ancestry, Cristina Simonet, MD, of Queen Mary University of London, and colleagues wrote in their paper, published in JAMA Neurology.
Additionally, data on how PD might manifest in different ethnic groups are limited, they said.
In their nested case-control, the researchers examined data from electronic health records of an ethnically diverse population of 1,016,277 adults seen in primary care practices between 1990 and Feb. 6, 2018. They compared individuals with PD with those without PD or other neurologic conditions.
The researchers identified 10 age and sex-matched controls for each PD case, and also conducted an unmatched analysis after adjusting for age and sex. The final study population included 1,055 patients with PD and 1,009,523 controls. The population of PD cases was 15.7% Black, 19.7% South Asian, 50.9% White, and 8.3% other; the population of controls was 13.3% Black, 21.5% South Asian, 43.7% White, and 11.3% other.
“We observed a constellation of symptoms noted by general practitioners up to a decade before diagnosis of PD,” the researchers said. Symptoms were identified across three time intervals (less than 2 years, 2-5 years, and 5-10 years before diagnosis) to better evaluate exposure outcome associations.
In the matched analysis of midlife risk factors, epilepsy showed the strongest association with PD diagnosis across all time periods, and type 2 diabetes or hypertension 5-10 years before diagnosis was associated with later PD.
Prediagnostic signs of PD included both motor and nonmotor manifestations.
The matched analysis revealed a significant increased association between tremor and memory symptoms less than 2 years before diagnosis (adjusted odds ratios of 151.24 and 8.73, respectively) as well as up to 10 years before diagnosis for tremors and up to 5 years for memory symptoms (aOR, 11.4 and 3.09, respectively) in PD patients, compared with controls.
Other strong associations between PD and early nonmotor features in cases, compared with controls, included hypotension (aOR, 6.81), constipation (aOR, 3.29), and depression (aOR, 4.61).
In addition, the researchers found associations for epilepsy that had not been identified in previous studies, and these associations persisted in a replication analysis.
The study findings were limited by several factors, mainly the use of routine primary care data with underascertained factors of interest, and potential mislabeling of PD, the researchers noted. Other limitations included the lack of data on prescription medication for PD, and the recording of memory problems in primary care without supportive testing to confirm cognitive impairment.
The results support a range of comorbidities and symptoms that may present in primary care, and clinicians should consider PD as a possible cause, the researchers wrote.
Make early referral a priority
The study is important because of the lack of diversity in Parkinson’s disease research, lead author Dr. Simonet said in an interview.
“Over the last decade, the global population suffering from Parkinson’s disease has more than doubled,” she said. Causes may include the increasing numbers of older people with longer life expectancy. “However, it seems there are other factors, including environmental, genetic, and lifestyle, that might play a role in increasing the prevalence of Parkinson’s disease.”
“More representative studies, including minority ethnic groups and those living in areas of high social and economic deprivation, are needed,” Dr. Simonet emphasized.
She said that there is little research on the association with epilepsy and hearing loss in early PD, and “for that reason, our results should encourage further studies to confirm a possible link between these manifestations and Parkinson’s disease.”
Early detection may drive better diagnoses
The current study is important for understanding the prediagnostic features and risk factors that may allow for earlier detection of Parkinson’s disease, William Hung, MD, a geriatrics and palliative care specialist of the Icahn School of Medicine at Mount Sinai, New York, said in an interview. “Prior to this study, there was limited understanding of these features.
“One surprise [in the findings] was that ethnicity and socioeconomic deprivation do not appear to be associated with the risk of PD, in contrast to other illnesses such as dementia,” said Dr. Hung. “The array of prediagnostic features associated with PD is not surprising, but nonetheless important for clinicians to know to consider whether PD could be the underlying cause.”
The take-home message for primary care is that “there are features, such as hearing loss, history of epilepsy, autonomic symptoms, motor symptoms, among others, for which clinicians should consider PD as part of the differential diagnosis as underlying cause and consider referral to specialists for diagnostic clarification,” said Dr. Hung.
“Additional research is needed to translate these findings to care, perhaps developing decision aids, interventions that may help with diagnosis and evaluation,” as is work on understanding the link between PD and symptoms such as hearing loss and epilepsy, he said.
Primary care offers opportunity to identify risk factors
The current study represents an important step in early recognition of PD, with implications for helping patients access treatments promptly and improve their quality of life, Bhavana Patel, DO, Shannon Chiu, MD, and Melissa J. Armstrong, MD, of the University of Florida, Gainesville, wrote in an accompanying editorial.
“The primary care setting is commonly where symptoms heralding the onset of PD are first discussed. However, little is known regarding the prediagnostic manifestations of PD that are seen in primary care clinics, particularly in underserved populations,” they wrote.
The study included many risk factors and prodromal markers associated with research criteria for prodromal PD, but did not include several risk and prodromal markers in the Movement Disorders Society research criteria, “such as symptoms suggestive of REM sleep behavior disorder, excessive daytime sleepiness (which overlaps with, but is distinct from, fatigue), urinary dysfunction, pesticide and solvent exposure, caffeine use, level of physical activity, and family history,” they said.
Even in individuals with diagnosed PD, certain symptoms, particularly nonmotor symptoms, are commonly underreported,” and primary care clinicians may not recognize these symptoms as PD risk factors, the authors noted.
However, “in addition to contributing to possible models of modifiable risk factors for PD, study results may also further inform algorithms designed to predict PD diagnoses in primary care,” they said. The study also highlights the need for more multivariable models to better identify PD risk factors and strategies for early identification of PD in primary care.
Several study coauthors received funding related to the study from Barts Charity, Health Data Research UK, the Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities, as well as the National Institute for Health Research UCLH Biomedical Research Centre. Lead author Dr. Simonet and Dr. Hung had no financial conflicts to disclose. Dr. Patel disclosed support from the National Institute on Aging, the Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia, and the American Brain Foundation and the Mary E. Groff Charitable Trust. Dr. Chiu reported receiving grants from Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia and the Smallwood Foundation. Dr. Armstrong disclosed funding from the National Institute on Aging, the Florida Department of Health, the Lewy Body Dementia Association, the Alzheimer’s Therapeutic Research Institute/Alzheimer’s Clinical Trial Consortium, the Alzheimer’s Disease Cooperative Study as Data Safety Monitoring Board the Parkinson’s Foundation, and the American Academy of Neurology.
Tremors and memory symptoms were identified among individuals in a primary care setting as early as 10 years before a Parkinson’s disease diagnosis in a new study.
Most research on the causes and early signs of Parkinson’s disease (PD) have involved patients of Northern European ancestry, Cristina Simonet, MD, of Queen Mary University of London, and colleagues wrote in their paper, published in JAMA Neurology.
Additionally, data on how PD might manifest in different ethnic groups are limited, they said.
In their nested case-control, the researchers examined data from electronic health records of an ethnically diverse population of 1,016,277 adults seen in primary care practices between 1990 and Feb. 6, 2018. They compared individuals with PD with those without PD or other neurologic conditions.
The researchers identified 10 age and sex-matched controls for each PD case, and also conducted an unmatched analysis after adjusting for age and sex. The final study population included 1,055 patients with PD and 1,009,523 controls. The population of PD cases was 15.7% Black, 19.7% South Asian, 50.9% White, and 8.3% other; the population of controls was 13.3% Black, 21.5% South Asian, 43.7% White, and 11.3% other.
“We observed a constellation of symptoms noted by general practitioners up to a decade before diagnosis of PD,” the researchers said. Symptoms were identified across three time intervals (less than 2 years, 2-5 years, and 5-10 years before diagnosis) to better evaluate exposure outcome associations.
In the matched analysis of midlife risk factors, epilepsy showed the strongest association with PD diagnosis across all time periods, and type 2 diabetes or hypertension 5-10 years before diagnosis was associated with later PD.
Prediagnostic signs of PD included both motor and nonmotor manifestations.
The matched analysis revealed a significant increased association between tremor and memory symptoms less than 2 years before diagnosis (adjusted odds ratios of 151.24 and 8.73, respectively) as well as up to 10 years before diagnosis for tremors and up to 5 years for memory symptoms (aOR, 11.4 and 3.09, respectively) in PD patients, compared with controls.
Other strong associations between PD and early nonmotor features in cases, compared with controls, included hypotension (aOR, 6.81), constipation (aOR, 3.29), and depression (aOR, 4.61).
In addition, the researchers found associations for epilepsy that had not been identified in previous studies, and these associations persisted in a replication analysis.
The study findings were limited by several factors, mainly the use of routine primary care data with underascertained factors of interest, and potential mislabeling of PD, the researchers noted. Other limitations included the lack of data on prescription medication for PD, and the recording of memory problems in primary care without supportive testing to confirm cognitive impairment.
The results support a range of comorbidities and symptoms that may present in primary care, and clinicians should consider PD as a possible cause, the researchers wrote.
Make early referral a priority
The study is important because of the lack of diversity in Parkinson’s disease research, lead author Dr. Simonet said in an interview.
“Over the last decade, the global population suffering from Parkinson’s disease has more than doubled,” she said. Causes may include the increasing numbers of older people with longer life expectancy. “However, it seems there are other factors, including environmental, genetic, and lifestyle, that might play a role in increasing the prevalence of Parkinson’s disease.”
“More representative studies, including minority ethnic groups and those living in areas of high social and economic deprivation, are needed,” Dr. Simonet emphasized.
She said that there is little research on the association with epilepsy and hearing loss in early PD, and “for that reason, our results should encourage further studies to confirm a possible link between these manifestations and Parkinson’s disease.”
Early detection may drive better diagnoses
The current study is important for understanding the prediagnostic features and risk factors that may allow for earlier detection of Parkinson’s disease, William Hung, MD, a geriatrics and palliative care specialist of the Icahn School of Medicine at Mount Sinai, New York, said in an interview. “Prior to this study, there was limited understanding of these features.
“One surprise [in the findings] was that ethnicity and socioeconomic deprivation do not appear to be associated with the risk of PD, in contrast to other illnesses such as dementia,” said Dr. Hung. “The array of prediagnostic features associated with PD is not surprising, but nonetheless important for clinicians to know to consider whether PD could be the underlying cause.”
The take-home message for primary care is that “there are features, such as hearing loss, history of epilepsy, autonomic symptoms, motor symptoms, among others, for which clinicians should consider PD as part of the differential diagnosis as underlying cause and consider referral to specialists for diagnostic clarification,” said Dr. Hung.
“Additional research is needed to translate these findings to care, perhaps developing decision aids, interventions that may help with diagnosis and evaluation,” as is work on understanding the link between PD and symptoms such as hearing loss and epilepsy, he said.
Primary care offers opportunity to identify risk factors
The current study represents an important step in early recognition of PD, with implications for helping patients access treatments promptly and improve their quality of life, Bhavana Patel, DO, Shannon Chiu, MD, and Melissa J. Armstrong, MD, of the University of Florida, Gainesville, wrote in an accompanying editorial.
“The primary care setting is commonly where symptoms heralding the onset of PD are first discussed. However, little is known regarding the prediagnostic manifestations of PD that are seen in primary care clinics, particularly in underserved populations,” they wrote.
The study included many risk factors and prodromal markers associated with research criteria for prodromal PD, but did not include several risk and prodromal markers in the Movement Disorders Society research criteria, “such as symptoms suggestive of REM sleep behavior disorder, excessive daytime sleepiness (which overlaps with, but is distinct from, fatigue), urinary dysfunction, pesticide and solvent exposure, caffeine use, level of physical activity, and family history,” they said.
Even in individuals with diagnosed PD, certain symptoms, particularly nonmotor symptoms, are commonly underreported,” and primary care clinicians may not recognize these symptoms as PD risk factors, the authors noted.
However, “in addition to contributing to possible models of modifiable risk factors for PD, study results may also further inform algorithms designed to predict PD diagnoses in primary care,” they said. The study also highlights the need for more multivariable models to better identify PD risk factors and strategies for early identification of PD in primary care.
Several study coauthors received funding related to the study from Barts Charity, Health Data Research UK, the Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities, as well as the National Institute for Health Research UCLH Biomedical Research Centre. Lead author Dr. Simonet and Dr. Hung had no financial conflicts to disclose. Dr. Patel disclosed support from the National Institute on Aging, the Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia, and the American Brain Foundation and the Mary E. Groff Charitable Trust. Dr. Chiu reported receiving grants from Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia and the Smallwood Foundation. Dr. Armstrong disclosed funding from the National Institute on Aging, the Florida Department of Health, the Lewy Body Dementia Association, the Alzheimer’s Therapeutic Research Institute/Alzheimer’s Clinical Trial Consortium, the Alzheimer’s Disease Cooperative Study as Data Safety Monitoring Board the Parkinson’s Foundation, and the American Academy of Neurology.
Tremors and memory symptoms were identified among individuals in a primary care setting as early as 10 years before a Parkinson’s disease diagnosis in a new study.
Most research on the causes and early signs of Parkinson’s disease (PD) have involved patients of Northern European ancestry, Cristina Simonet, MD, of Queen Mary University of London, and colleagues wrote in their paper, published in JAMA Neurology.
Additionally, data on how PD might manifest in different ethnic groups are limited, they said.
In their nested case-control, the researchers examined data from electronic health records of an ethnically diverse population of 1,016,277 adults seen in primary care practices between 1990 and Feb. 6, 2018. They compared individuals with PD with those without PD or other neurologic conditions.
The researchers identified 10 age and sex-matched controls for each PD case, and also conducted an unmatched analysis after adjusting for age and sex. The final study population included 1,055 patients with PD and 1,009,523 controls. The population of PD cases was 15.7% Black, 19.7% South Asian, 50.9% White, and 8.3% other; the population of controls was 13.3% Black, 21.5% South Asian, 43.7% White, and 11.3% other.
“We observed a constellation of symptoms noted by general practitioners up to a decade before diagnosis of PD,” the researchers said. Symptoms were identified across three time intervals (less than 2 years, 2-5 years, and 5-10 years before diagnosis) to better evaluate exposure outcome associations.
In the matched analysis of midlife risk factors, epilepsy showed the strongest association with PD diagnosis across all time periods, and type 2 diabetes or hypertension 5-10 years before diagnosis was associated with later PD.
Prediagnostic signs of PD included both motor and nonmotor manifestations.
The matched analysis revealed a significant increased association between tremor and memory symptoms less than 2 years before diagnosis (adjusted odds ratios of 151.24 and 8.73, respectively) as well as up to 10 years before diagnosis for tremors and up to 5 years for memory symptoms (aOR, 11.4 and 3.09, respectively) in PD patients, compared with controls.
Other strong associations between PD and early nonmotor features in cases, compared with controls, included hypotension (aOR, 6.81), constipation (aOR, 3.29), and depression (aOR, 4.61).
In addition, the researchers found associations for epilepsy that had not been identified in previous studies, and these associations persisted in a replication analysis.
The study findings were limited by several factors, mainly the use of routine primary care data with underascertained factors of interest, and potential mislabeling of PD, the researchers noted. Other limitations included the lack of data on prescription medication for PD, and the recording of memory problems in primary care without supportive testing to confirm cognitive impairment.
The results support a range of comorbidities and symptoms that may present in primary care, and clinicians should consider PD as a possible cause, the researchers wrote.
Make early referral a priority
The study is important because of the lack of diversity in Parkinson’s disease research, lead author Dr. Simonet said in an interview.
“Over the last decade, the global population suffering from Parkinson’s disease has more than doubled,” she said. Causes may include the increasing numbers of older people with longer life expectancy. “However, it seems there are other factors, including environmental, genetic, and lifestyle, that might play a role in increasing the prevalence of Parkinson’s disease.”
“More representative studies, including minority ethnic groups and those living in areas of high social and economic deprivation, are needed,” Dr. Simonet emphasized.
She said that there is little research on the association with epilepsy and hearing loss in early PD, and “for that reason, our results should encourage further studies to confirm a possible link between these manifestations and Parkinson’s disease.”
Early detection may drive better diagnoses
The current study is important for understanding the prediagnostic features and risk factors that may allow for earlier detection of Parkinson’s disease, William Hung, MD, a geriatrics and palliative care specialist of the Icahn School of Medicine at Mount Sinai, New York, said in an interview. “Prior to this study, there was limited understanding of these features.
“One surprise [in the findings] was that ethnicity and socioeconomic deprivation do not appear to be associated with the risk of PD, in contrast to other illnesses such as dementia,” said Dr. Hung. “The array of prediagnostic features associated with PD is not surprising, but nonetheless important for clinicians to know to consider whether PD could be the underlying cause.”
The take-home message for primary care is that “there are features, such as hearing loss, history of epilepsy, autonomic symptoms, motor symptoms, among others, for which clinicians should consider PD as part of the differential diagnosis as underlying cause and consider referral to specialists for diagnostic clarification,” said Dr. Hung.
“Additional research is needed to translate these findings to care, perhaps developing decision aids, interventions that may help with diagnosis and evaluation,” as is work on understanding the link between PD and symptoms such as hearing loss and epilepsy, he said.
Primary care offers opportunity to identify risk factors
The current study represents an important step in early recognition of PD, with implications for helping patients access treatments promptly and improve their quality of life, Bhavana Patel, DO, Shannon Chiu, MD, and Melissa J. Armstrong, MD, of the University of Florida, Gainesville, wrote in an accompanying editorial.
“The primary care setting is commonly where symptoms heralding the onset of PD are first discussed. However, little is known regarding the prediagnostic manifestations of PD that are seen in primary care clinics, particularly in underserved populations,” they wrote.
The study included many risk factors and prodromal markers associated with research criteria for prodromal PD, but did not include several risk and prodromal markers in the Movement Disorders Society research criteria, “such as symptoms suggestive of REM sleep behavior disorder, excessive daytime sleepiness (which overlaps with, but is distinct from, fatigue), urinary dysfunction, pesticide and solvent exposure, caffeine use, level of physical activity, and family history,” they said.
Even in individuals with diagnosed PD, certain symptoms, particularly nonmotor symptoms, are commonly underreported,” and primary care clinicians may not recognize these symptoms as PD risk factors, the authors noted.
However, “in addition to contributing to possible models of modifiable risk factors for PD, study results may also further inform algorithms designed to predict PD diagnoses in primary care,” they said. The study also highlights the need for more multivariable models to better identify PD risk factors and strategies for early identification of PD in primary care.
Several study coauthors received funding related to the study from Barts Charity, Health Data Research UK, the Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities, as well as the National Institute for Health Research UCLH Biomedical Research Centre. Lead author Dr. Simonet and Dr. Hung had no financial conflicts to disclose. Dr. Patel disclosed support from the National Institute on Aging, the Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia, and the American Brain Foundation and the Mary E. Groff Charitable Trust. Dr. Chiu reported receiving grants from Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia and the Smallwood Foundation. Dr. Armstrong disclosed funding from the National Institute on Aging, the Florida Department of Health, the Lewy Body Dementia Association, the Alzheimer’s Therapeutic Research Institute/Alzheimer’s Clinical Trial Consortium, the Alzheimer’s Disease Cooperative Study as Data Safety Monitoring Board the Parkinson’s Foundation, and the American Academy of Neurology.
FROM JAMA NEUROLOGY
Imaging links insula and frontal cortex to anxiety in Parkinson’s disease
Anxiety occurs in approximately 31% of Parkinson’s disease patients, but the underlying mechanisms are not well understood, wrote Nacim Betrouni, MD, of the University of Lille, France, and colleagues. Previous research has shown associations between anxiety severity and increased activity in brain areas of emotion processing, based on MRI and positron emission tomography, but electroencephalography (EEG) has not been widely used, they said.
In a study published in Neurophysiologie Clinique , the researchers compared EEG spectral patterns and functional resting-state networks in Parkinson’s disease patients with and without anxiety disorders. They identified data from 33 PD patients who met criteria for anxiety, and 75 without anxiety. The average age of the patients was 65 years, and the average disease duration was 9.76 years in anxiety patients and 7.83 years in patients without anxiety.
Overall, findings on spectral analysis showed an association between anxiety and changes in the alpha activity in the right frontal cortex, the researchers said. They also found the relative power in the alpha1 frequency band in the right prefrontal cortex was lower in patients with anxiety than without; this finding was significantly associated with avoidance behavior on a subscale of the Parkinson’s Anxiety Scale (PAS_C, P = .035). A trend toward a significant association with episodic anxiety was noted (PAS_B, P = .06), but no significant associations were noted for persistent anxiety or the total scale score.
The imaging also showed an increased connectivity between the insula and the posterior cingulate cortex in several frequency bands in the anxiety patients, the researchers said. “The increased connectivity observed here may be a marker of the maintenance of avoidance behaviors that characterize anxiety in PD,” they noted.
The study findings were limited by several factors including the small and unbalanced proportion of the study population with anxiety, and the consideration of global anxiety only, without distinguishing anxiety subtypes, the researchers noted. Another limitation was the use only of static EEC patterns, without using dynamic patterns, they said.
The study is the first known to use EEG to explore the mechanisms of PD-related anxiety and “the reported results provide new insights, supporting findings of previous studies using other modalities, mainly rs-fMRI, and show that EEG could be a relevant technique to explore these disorders,” the researchers wrote.
However, more research is needed to confirm the findings in patients with a larger panel of anxiety disorders, they concluded.
The study was supported by the Michael J. Fox Foundation. The researchers had no financial conflicts to disclose.
Anxiety occurs in approximately 31% of Parkinson’s disease patients, but the underlying mechanisms are not well understood, wrote Nacim Betrouni, MD, of the University of Lille, France, and colleagues. Previous research has shown associations between anxiety severity and increased activity in brain areas of emotion processing, based on MRI and positron emission tomography, but electroencephalography (EEG) has not been widely used, they said.
In a study published in Neurophysiologie Clinique , the researchers compared EEG spectral patterns and functional resting-state networks in Parkinson’s disease patients with and without anxiety disorders. They identified data from 33 PD patients who met criteria for anxiety, and 75 without anxiety. The average age of the patients was 65 years, and the average disease duration was 9.76 years in anxiety patients and 7.83 years in patients without anxiety.
Overall, findings on spectral analysis showed an association between anxiety and changes in the alpha activity in the right frontal cortex, the researchers said. They also found the relative power in the alpha1 frequency band in the right prefrontal cortex was lower in patients with anxiety than without; this finding was significantly associated with avoidance behavior on a subscale of the Parkinson’s Anxiety Scale (PAS_C, P = .035). A trend toward a significant association with episodic anxiety was noted (PAS_B, P = .06), but no significant associations were noted for persistent anxiety or the total scale score.
The imaging also showed an increased connectivity between the insula and the posterior cingulate cortex in several frequency bands in the anxiety patients, the researchers said. “The increased connectivity observed here may be a marker of the maintenance of avoidance behaviors that characterize anxiety in PD,” they noted.
The study findings were limited by several factors including the small and unbalanced proportion of the study population with anxiety, and the consideration of global anxiety only, without distinguishing anxiety subtypes, the researchers noted. Another limitation was the use only of static EEC patterns, without using dynamic patterns, they said.
The study is the first known to use EEG to explore the mechanisms of PD-related anxiety and “the reported results provide new insights, supporting findings of previous studies using other modalities, mainly rs-fMRI, and show that EEG could be a relevant technique to explore these disorders,” the researchers wrote.
However, more research is needed to confirm the findings in patients with a larger panel of anxiety disorders, they concluded.
The study was supported by the Michael J. Fox Foundation. The researchers had no financial conflicts to disclose.
Anxiety occurs in approximately 31% of Parkinson’s disease patients, but the underlying mechanisms are not well understood, wrote Nacim Betrouni, MD, of the University of Lille, France, and colleagues. Previous research has shown associations between anxiety severity and increased activity in brain areas of emotion processing, based on MRI and positron emission tomography, but electroencephalography (EEG) has not been widely used, they said.
In a study published in Neurophysiologie Clinique , the researchers compared EEG spectral patterns and functional resting-state networks in Parkinson’s disease patients with and without anxiety disorders. They identified data from 33 PD patients who met criteria for anxiety, and 75 without anxiety. The average age of the patients was 65 years, and the average disease duration was 9.76 years in anxiety patients and 7.83 years in patients without anxiety.
Overall, findings on spectral analysis showed an association between anxiety and changes in the alpha activity in the right frontal cortex, the researchers said. They also found the relative power in the alpha1 frequency band in the right prefrontal cortex was lower in patients with anxiety than without; this finding was significantly associated with avoidance behavior on a subscale of the Parkinson’s Anxiety Scale (PAS_C, P = .035). A trend toward a significant association with episodic anxiety was noted (PAS_B, P = .06), but no significant associations were noted for persistent anxiety or the total scale score.
The imaging also showed an increased connectivity between the insula and the posterior cingulate cortex in several frequency bands in the anxiety patients, the researchers said. “The increased connectivity observed here may be a marker of the maintenance of avoidance behaviors that characterize anxiety in PD,” they noted.
The study findings were limited by several factors including the small and unbalanced proportion of the study population with anxiety, and the consideration of global anxiety only, without distinguishing anxiety subtypes, the researchers noted. Another limitation was the use only of static EEC patterns, without using dynamic patterns, they said.
The study is the first known to use EEG to explore the mechanisms of PD-related anxiety and “the reported results provide new insights, supporting findings of previous studies using other modalities, mainly rs-fMRI, and show that EEG could be a relevant technique to explore these disorders,” the researchers wrote.
However, more research is needed to confirm the findings in patients with a larger panel of anxiety disorders, they concluded.
The study was supported by the Michael J. Fox Foundation. The researchers had no financial conflicts to disclose.
FROM NEUROPHYSIOLOGIE CLINIQUE
Berries, red wine linked to lower mortality in Parkinson’s disease
(PD), new research suggests.
In a prospective analysis of more than 1,200 participants with an eventual PD diagnosis, those who ate three or more servings of flavonoid-rich foods a week had a 70% lower mortality versus those consuming one or fewer servings of such foods per month.
“Adopting a healthy dietary pattern that is high in colorful fruits and veggies like berries, even after a Parkinson diagnosis, could slow disease progression and improve survival rate,” study investigator Xiang Gao, MD, PhD, professor and director, Nutritional Epidemiology Lab, department of nutritional sciences, Penn State University, University Park, said in an interview.
The findings were published online Jan. 26, 2022, in Neurology.
First evidence of survival advantage
Flavonoids are plant-derived polyphenolic molecules found in fruits such as berries, apples, and oranges; vegetables such as kale and broccoli; and beverages, including tea and red wine. They are the dietary components that give many foods their vibrant color.
Certain flavonoids have been shown previously to have antioxidant and anti-inflammatory properties.
A previous study by Dr. Gao and colleagues showed that flavonoids were associated with a lower future risk for developing PD. However, it did not provide evidence these nutrients improved survival rates among PD patients.
The new analysis included participants from the ongoing Nurses’ Health Study (NHS) of female registered nurses, which began in 1976, and male participants from the ongoing Health Professionals Follow-up Study (HPFS), which began in 1986.
All participants answered questionnaires at baseline and then biennially to update information on demographics, lifestyle, medical history, and occurrence of chronic disease.
Using validated food-frequency questionnaires completed every 4 years, researchers assessed dietary intakes of total flavonoid, six flavonoid subclasses, and flavonoid-rich foods such as tea, apples, berries, oranges and orange juice, and red wine.
They examined flavonoid intake both before and after a PD diagnosis to minimize the potential for reverse causality. The investigators noted that patients with PD have difficulty swallowing and handling food and cutlery, which could impact their consumption of flavonoid-rich foods.
Frequency of consumption of flavonoid-rich foods was categorized into four groups: one or less servings per month (the reference group), one to three servings per month, one to two servings per week, and three or more servings per week.
The analysis included 599 women and 652 men who were newly diagnosed with PD. The mean age at PD diagnosis was 72 years, and the mean time between the last prediagnosis dietary assessment and PD diagnosis was 32 months.
The primary outcome measure was all-cause mortality. There were 528 deaths in men and 416 deaths in women during an average of 33 years of follow-up.
Neuroprotective pathway?
After controlling for age, lifestyle behaviors, medical history, and total energy and caffeine intake, results showed that higher total flavonoid intake before PD diagnosis was associated with a lower risk for all-cause mortality after diagnosis in men, with a hazard ratio of 0.53 (95% confidence interval, 0.39-0.71) when comparing the highest and lowest quartiles (P for trend < .001).
However, this association was not found in women (HR, 0.93; 95% CI, 0.68-1.28; P for trend = .69).
The pooled HR was 0.70 (95% CI, 0.40-1.22; P for trend = .25) with significant heterogeneity (P = .01).
There were significant associations between a higher prediagnosis intake of certain flavonoids and lower mortality risk. The pooled HR comparing the highest versus lowest intake quartiles was 0.66 for anthocyanin, 0.78 for flavones, and 0.69 for flavan-3-ols (P < .05 for all).
Compared with participants who consumed less than one serving a month, those consuming more than three servings a week prediagnosis of berries or red wine had a lower mortality risk (pooled HR, 0.77; 95% CI, 0.58-1.02 for berries and HR, 0.68; 95% CI, 0.51-0.91 for red wine).
After PD diagnosis, higher flavonoid consumption was associated with better survival rates in both men and women.
It’s unclear why there was a gender difference in the association between prediagnosis flavonoid intake and mortality but not for postdiagnosis flavonoid intakes, Dr. Gao said.
A potential neuroprotective pathway by which flavonoids reduce mortality in PD involves direct radical scavenging, which lowers oxidative stress and chronic neuroinflammation levels, he noted.
“Certain flavonoids, for example, anthocyanins, have been shown to exert antiapoptosis effects and protect cognition and motor functions. They could also increase dopamine release,” Dr. Gao added.
Study limitations included not having detailed information on participants’ PD disease severity and that both the NHS and HPFS include predominantly White health care professionals, which limits the generalizability of the results, the investigators noted.
No direct link
Commenting on the findings, Michael S. Okun, MD, medical advisor at the Parkinson’s Foundation and director of the Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, said the study adds to growing evidence suggesting “subsets of flavonoids and especially berries and wine will have benefits pre- and post–Parkinson’s disease diagnosis.”
However, he emphasized that patients should not take up drinking red wine just to improve survival.
“We don’t recommend that folks who are already diagnosed with Parkinson’s drink alcohol, especially without physician supervision,” said Dr. Okun, who was not involved with the research.
Also commenting for this article, Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England), said because the study doesn’t appear to adjust for socioeconomic status, the results may be driven by factors such as income and education and not food intake.
The study found a beneficial association with anthocyanins, which are mainly found in expensive berries, and with flavan-3-ols found mainly in tea, which in the United States is often a marker of higher income, said Dr. Kuhnle.
The advantage of assessing dietary intake of flavonoids using a food-frequency questionnaire, as was done in this study, is that it captures long-term patterns. However, the disadvantage is a loss in “resolution” by combining similar foods, Dr. Kuhnle noted.
Since flavonoids are found in most fruits and vegetables, high flavonoid intake “might simply be a marker of fruit and vegetable intake and therefore a ‘healthy’ dietary pattern,” he concluded.
The study received funding from the National Institute of Neurological Disorders and Stroke. Dr. Gao and Dr. Okun reported no relevant financial relationships. Dr. Kuhnle has conducted research into the associations between flavanol and health, some of which has been funded by Mars.
A version of this article first appeared on Medscape.com.
(PD), new research suggests.
In a prospective analysis of more than 1,200 participants with an eventual PD diagnosis, those who ate three or more servings of flavonoid-rich foods a week had a 70% lower mortality versus those consuming one or fewer servings of such foods per month.
“Adopting a healthy dietary pattern that is high in colorful fruits and veggies like berries, even after a Parkinson diagnosis, could slow disease progression and improve survival rate,” study investigator Xiang Gao, MD, PhD, professor and director, Nutritional Epidemiology Lab, department of nutritional sciences, Penn State University, University Park, said in an interview.
The findings were published online Jan. 26, 2022, in Neurology.
First evidence of survival advantage
Flavonoids are plant-derived polyphenolic molecules found in fruits such as berries, apples, and oranges; vegetables such as kale and broccoli; and beverages, including tea and red wine. They are the dietary components that give many foods their vibrant color.
Certain flavonoids have been shown previously to have antioxidant and anti-inflammatory properties.
A previous study by Dr. Gao and colleagues showed that flavonoids were associated with a lower future risk for developing PD. However, it did not provide evidence these nutrients improved survival rates among PD patients.
The new analysis included participants from the ongoing Nurses’ Health Study (NHS) of female registered nurses, which began in 1976, and male participants from the ongoing Health Professionals Follow-up Study (HPFS), which began in 1986.
All participants answered questionnaires at baseline and then biennially to update information on demographics, lifestyle, medical history, and occurrence of chronic disease.
Using validated food-frequency questionnaires completed every 4 years, researchers assessed dietary intakes of total flavonoid, six flavonoid subclasses, and flavonoid-rich foods such as tea, apples, berries, oranges and orange juice, and red wine.
They examined flavonoid intake both before and after a PD diagnosis to minimize the potential for reverse causality. The investigators noted that patients with PD have difficulty swallowing and handling food and cutlery, which could impact their consumption of flavonoid-rich foods.
Frequency of consumption of flavonoid-rich foods was categorized into four groups: one or less servings per month (the reference group), one to three servings per month, one to two servings per week, and three or more servings per week.
The analysis included 599 women and 652 men who were newly diagnosed with PD. The mean age at PD diagnosis was 72 years, and the mean time between the last prediagnosis dietary assessment and PD diagnosis was 32 months.
The primary outcome measure was all-cause mortality. There were 528 deaths in men and 416 deaths in women during an average of 33 years of follow-up.
Neuroprotective pathway?
After controlling for age, lifestyle behaviors, medical history, and total energy and caffeine intake, results showed that higher total flavonoid intake before PD diagnosis was associated with a lower risk for all-cause mortality after diagnosis in men, with a hazard ratio of 0.53 (95% confidence interval, 0.39-0.71) when comparing the highest and lowest quartiles (P for trend < .001).
However, this association was not found in women (HR, 0.93; 95% CI, 0.68-1.28; P for trend = .69).
The pooled HR was 0.70 (95% CI, 0.40-1.22; P for trend = .25) with significant heterogeneity (P = .01).
There were significant associations between a higher prediagnosis intake of certain flavonoids and lower mortality risk. The pooled HR comparing the highest versus lowest intake quartiles was 0.66 for anthocyanin, 0.78 for flavones, and 0.69 for flavan-3-ols (P < .05 for all).
Compared with participants who consumed less than one serving a month, those consuming more than three servings a week prediagnosis of berries or red wine had a lower mortality risk (pooled HR, 0.77; 95% CI, 0.58-1.02 for berries and HR, 0.68; 95% CI, 0.51-0.91 for red wine).
After PD diagnosis, higher flavonoid consumption was associated with better survival rates in both men and women.
It’s unclear why there was a gender difference in the association between prediagnosis flavonoid intake and mortality but not for postdiagnosis flavonoid intakes, Dr. Gao said.
A potential neuroprotective pathway by which flavonoids reduce mortality in PD involves direct radical scavenging, which lowers oxidative stress and chronic neuroinflammation levels, he noted.
“Certain flavonoids, for example, anthocyanins, have been shown to exert antiapoptosis effects and protect cognition and motor functions. They could also increase dopamine release,” Dr. Gao added.
Study limitations included not having detailed information on participants’ PD disease severity and that both the NHS and HPFS include predominantly White health care professionals, which limits the generalizability of the results, the investigators noted.
No direct link
Commenting on the findings, Michael S. Okun, MD, medical advisor at the Parkinson’s Foundation and director of the Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, said the study adds to growing evidence suggesting “subsets of flavonoids and especially berries and wine will have benefits pre- and post–Parkinson’s disease diagnosis.”
However, he emphasized that patients should not take up drinking red wine just to improve survival.
“We don’t recommend that folks who are already diagnosed with Parkinson’s drink alcohol, especially without physician supervision,” said Dr. Okun, who was not involved with the research.
Also commenting for this article, Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England), said because the study doesn’t appear to adjust for socioeconomic status, the results may be driven by factors such as income and education and not food intake.
The study found a beneficial association with anthocyanins, which are mainly found in expensive berries, and with flavan-3-ols found mainly in tea, which in the United States is often a marker of higher income, said Dr. Kuhnle.
The advantage of assessing dietary intake of flavonoids using a food-frequency questionnaire, as was done in this study, is that it captures long-term patterns. However, the disadvantage is a loss in “resolution” by combining similar foods, Dr. Kuhnle noted.
Since flavonoids are found in most fruits and vegetables, high flavonoid intake “might simply be a marker of fruit and vegetable intake and therefore a ‘healthy’ dietary pattern,” he concluded.
The study received funding from the National Institute of Neurological Disorders and Stroke. Dr. Gao and Dr. Okun reported no relevant financial relationships. Dr. Kuhnle has conducted research into the associations between flavanol and health, some of which has been funded by Mars.
A version of this article first appeared on Medscape.com.
(PD), new research suggests.
In a prospective analysis of more than 1,200 participants with an eventual PD diagnosis, those who ate three or more servings of flavonoid-rich foods a week had a 70% lower mortality versus those consuming one or fewer servings of such foods per month.
“Adopting a healthy dietary pattern that is high in colorful fruits and veggies like berries, even after a Parkinson diagnosis, could slow disease progression and improve survival rate,” study investigator Xiang Gao, MD, PhD, professor and director, Nutritional Epidemiology Lab, department of nutritional sciences, Penn State University, University Park, said in an interview.
The findings were published online Jan. 26, 2022, in Neurology.
First evidence of survival advantage
Flavonoids are plant-derived polyphenolic molecules found in fruits such as berries, apples, and oranges; vegetables such as kale and broccoli; and beverages, including tea and red wine. They are the dietary components that give many foods their vibrant color.
Certain flavonoids have been shown previously to have antioxidant and anti-inflammatory properties.
A previous study by Dr. Gao and colleagues showed that flavonoids were associated with a lower future risk for developing PD. However, it did not provide evidence these nutrients improved survival rates among PD patients.
The new analysis included participants from the ongoing Nurses’ Health Study (NHS) of female registered nurses, which began in 1976, and male participants from the ongoing Health Professionals Follow-up Study (HPFS), which began in 1986.
All participants answered questionnaires at baseline and then biennially to update information on demographics, lifestyle, medical history, and occurrence of chronic disease.
Using validated food-frequency questionnaires completed every 4 years, researchers assessed dietary intakes of total flavonoid, six flavonoid subclasses, and flavonoid-rich foods such as tea, apples, berries, oranges and orange juice, and red wine.
They examined flavonoid intake both before and after a PD diagnosis to minimize the potential for reverse causality. The investigators noted that patients with PD have difficulty swallowing and handling food and cutlery, which could impact their consumption of flavonoid-rich foods.
Frequency of consumption of flavonoid-rich foods was categorized into four groups: one or less servings per month (the reference group), one to three servings per month, one to two servings per week, and three or more servings per week.
The analysis included 599 women and 652 men who were newly diagnosed with PD. The mean age at PD diagnosis was 72 years, and the mean time between the last prediagnosis dietary assessment and PD diagnosis was 32 months.
The primary outcome measure was all-cause mortality. There were 528 deaths in men and 416 deaths in women during an average of 33 years of follow-up.
Neuroprotective pathway?
After controlling for age, lifestyle behaviors, medical history, and total energy and caffeine intake, results showed that higher total flavonoid intake before PD diagnosis was associated with a lower risk for all-cause mortality after diagnosis in men, with a hazard ratio of 0.53 (95% confidence interval, 0.39-0.71) when comparing the highest and lowest quartiles (P for trend < .001).
However, this association was not found in women (HR, 0.93; 95% CI, 0.68-1.28; P for trend = .69).
The pooled HR was 0.70 (95% CI, 0.40-1.22; P for trend = .25) with significant heterogeneity (P = .01).
There were significant associations between a higher prediagnosis intake of certain flavonoids and lower mortality risk. The pooled HR comparing the highest versus lowest intake quartiles was 0.66 for anthocyanin, 0.78 for flavones, and 0.69 for flavan-3-ols (P < .05 for all).
Compared with participants who consumed less than one serving a month, those consuming more than three servings a week prediagnosis of berries or red wine had a lower mortality risk (pooled HR, 0.77; 95% CI, 0.58-1.02 for berries and HR, 0.68; 95% CI, 0.51-0.91 for red wine).
After PD diagnosis, higher flavonoid consumption was associated with better survival rates in both men and women.
It’s unclear why there was a gender difference in the association between prediagnosis flavonoid intake and mortality but not for postdiagnosis flavonoid intakes, Dr. Gao said.
A potential neuroprotective pathway by which flavonoids reduce mortality in PD involves direct radical scavenging, which lowers oxidative stress and chronic neuroinflammation levels, he noted.
“Certain flavonoids, for example, anthocyanins, have been shown to exert antiapoptosis effects and protect cognition and motor functions. They could also increase dopamine release,” Dr. Gao added.
Study limitations included not having detailed information on participants’ PD disease severity and that both the NHS and HPFS include predominantly White health care professionals, which limits the generalizability of the results, the investigators noted.
No direct link
Commenting on the findings, Michael S. Okun, MD, medical advisor at the Parkinson’s Foundation and director of the Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, said the study adds to growing evidence suggesting “subsets of flavonoids and especially berries and wine will have benefits pre- and post–Parkinson’s disease diagnosis.”
However, he emphasized that patients should not take up drinking red wine just to improve survival.
“We don’t recommend that folks who are already diagnosed with Parkinson’s drink alcohol, especially without physician supervision,” said Dr. Okun, who was not involved with the research.
Also commenting for this article, Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England), said because the study doesn’t appear to adjust for socioeconomic status, the results may be driven by factors such as income and education and not food intake.
The study found a beneficial association with anthocyanins, which are mainly found in expensive berries, and with flavan-3-ols found mainly in tea, which in the United States is often a marker of higher income, said Dr. Kuhnle.
The advantage of assessing dietary intake of flavonoids using a food-frequency questionnaire, as was done in this study, is that it captures long-term patterns. However, the disadvantage is a loss in “resolution” by combining similar foods, Dr. Kuhnle noted.
Since flavonoids are found in most fruits and vegetables, high flavonoid intake “might simply be a marker of fruit and vegetable intake and therefore a ‘healthy’ dietary pattern,” he concluded.
The study received funding from the National Institute of Neurological Disorders and Stroke. Dr. Gao and Dr. Okun reported no relevant financial relationships. Dr. Kuhnle has conducted research into the associations between flavanol and health, some of which has been funded by Mars.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Dairy intake may increase risk of Parkinson’s disease in men
according to investigators. Men of European ancestry with a genetic marker predicting dairy consumption had significantly greater risk of Parkinson’s disease than individuals without the marker, suggesting a causal relationship between dairy intake and Parkinson’s disease, lead author Cloé Domenighetti, MSc, a PhD student at UVSQ, Université Paris Sud, and colleagues reported.
“Previous studies highlighted dairy intake as a risk factor of Parkinson’s disease,” the investigators wrote in Movement Disorders. “A meta-analysis of prospective studies reported a 40% increased Parkinson’s disease risk in participants with the highest intake. It is unclear whether the association is causal or explained by confounding or reverse causation, given the long prodromal phase of Parkinson’s disease.”
A Mendelian randomization study
The investigators evaluated this link by comparing 9,823 cases of Parkinson’s disease with 8,376 controls, all individuals of European ancestry from the Courage-Parkinson’s disease consortium, comprising 23 studies. Data were analyzed by two-sample Mendelian randomization, a technique that uses genotype to predict behavior, thereby replacing conventional methods of capturing behavior, such as questionnaires. In this case, the investigators screened all participants for rs4988235, a single-nucleotide polymorphism (SNP) upstream of the lactase gene that is well documented to predict dairy intake among individuals of European ancestry.
“Mendelian randomization uses genetic variants associated with exposures as instrumental variables to estimate causal relationships between exposures and outcomes,” the investigators wrote. “Mendelian randomization analyses are less likely to be biased by confounding or reverse causation than observational studies if a set of assumptions are met.”
The approach uncovered a significant association between rs4988235 and Parkinson’s disease, with a 70% increase in disease risk per one serving of dairy per day (odds ratio, 1.70; 95% confidence interval, 1.12-2.60; P = .013). Further analysis revealed that this finding was driven by men, who had a 2.5-fold increased risk of Parkinson’s disease per one serving per day (OR, 2.50; 95% CI, 1.37-4.56; P = .003) versus women, among whom there was no significant association (OR, 1.04; 95% CI, 0.56-1.92; P = .91). No significant associations were observed among individuals grouped by age or Parkinson’s disease duration.
“Our findings suggest that dairy intake increases Parkinson’s disease risk,” the investigators concluded. “Therefore, diets with limited milk intake (e.g., Mediterranean diet) may be beneficial with respect to Parkinson’s disease.”
Further evidence supporting a link between diet and Parkinson’s disease
According to Silke Appel-Cresswell, MD, Marg Meikle Professor for Parkinson’s Research at the University of British Columbia, Vancouver, the findings align with previous prospective cohort studies demonstrating an increased risk of Parkinson’s disease with greater consumption of dairy.
“What the current study adds,” Dr. Appel-Cresswell said, “is a complementary approach to assess the association where the risk of reverse causation and of confounding are minimized. Like in some of the previous studies, the authors find sex differences with an increased risk for men but not women.”
Dr. Appel-Cresswell noted that an increasing body of evidence supports a link between diet and Parkinson’s disease, including a study of her own published last year, which showed later onset of Parkinson’s disease among individuals with a Mediterranean-style diet.
“We are accumulating evidence for a role of diet (or more broadly, the food exposome) for the risk to develop Parkinson’s disease,” Dr. Appel-Cresswell said, noting that “key pieces are still missing, including mechanisms underlying associations, clinical trials in individuals with established Parkinson’s disease and – eventually – preventive interventions. This research is urgently needed and analyses will need to take sex differences and a large range of potential other factors into account.”
A ‘modest’ contributing factor?
Vikas Kotagal, MD, associate professor of neurology at the University of Michigan, Ann Arbor, offered a perspective on the study methodology, and suggested that a causal link between dairy intake and Parkinson’s disease, if present, is likely minimal.
“Limitations to the study include the fact that participants weren’t actually asked or tested for how much dairy they truly consumed,” Dr. Kotagal said*. “Their dairy intake was estimated based on their genetic background – there are certainly many assumptions baked into this analytic approach which may or may not be true. It is also worth noting the fact that this causal association was seen in men and not women, suggesting that even if dairy intake was truly causal, it is likely to be a modest contributing factor and not a significant cause of Parkinson’s disease in the broader population in general.”
Still, Dr. Kotagal agreed with Dr. Appel-Cresswell that underlying mechanisms need further investigation.
“The biggest takeaway here is to heighten the urgency for researchers and funders to explore whether factors that might cluster with dairy intake – including pesticide exposure in milk or even the make-up of bacterial populations in different peoples’ intestines – might deserve closer scrutiny as a missing link connecting dairy consumption to increased Parkinson’s disease risk,” Dr. Kotagal said.
Dietary advice
Considering all available evidence, Dr. Appel-Cresswell offered some dietary advice with benefits that may extend beyond prevention of Parkinson’s disease.
“From a clinical point of view, I suggest to limit dairy intake to a moderate amount,” she said. “Mediterranean diets so far have the best supporting evidence for a lower Parkinson’s disease risk, although data is lacking for benefits in established Parkinson’s disease. Given the low risk of the Mediterranean diet and the established benefits for a host of other medical conditions, this is generally a safe and delicious recommendation whether one is living with Parkinson’s or not.”
The study was supported by the European Union Joint Program for Neurodegenerative Disease Research, the National Centre of Excellence in Research on Parkinson’s Disease, the National Institutes of Health, and others. The investigators disclosed additional relationships with Astellas Pharma, Sanofi, Pfizer, and others. Dr. Kotagal and Dr. Appel-Cresswell reported no relevant conflicts of interest.
*Correction, 2/10/22: An earlier version of this article misstated Dr. Kotagal's name in certain instances, including a photo caption.
according to investigators. Men of European ancestry with a genetic marker predicting dairy consumption had significantly greater risk of Parkinson’s disease than individuals without the marker, suggesting a causal relationship between dairy intake and Parkinson’s disease, lead author Cloé Domenighetti, MSc, a PhD student at UVSQ, Université Paris Sud, and colleagues reported.
“Previous studies highlighted dairy intake as a risk factor of Parkinson’s disease,” the investigators wrote in Movement Disorders. “A meta-analysis of prospective studies reported a 40% increased Parkinson’s disease risk in participants with the highest intake. It is unclear whether the association is causal or explained by confounding or reverse causation, given the long prodromal phase of Parkinson’s disease.”
A Mendelian randomization study
The investigators evaluated this link by comparing 9,823 cases of Parkinson’s disease with 8,376 controls, all individuals of European ancestry from the Courage-Parkinson’s disease consortium, comprising 23 studies. Data were analyzed by two-sample Mendelian randomization, a technique that uses genotype to predict behavior, thereby replacing conventional methods of capturing behavior, such as questionnaires. In this case, the investigators screened all participants for rs4988235, a single-nucleotide polymorphism (SNP) upstream of the lactase gene that is well documented to predict dairy intake among individuals of European ancestry.
“Mendelian randomization uses genetic variants associated with exposures as instrumental variables to estimate causal relationships between exposures and outcomes,” the investigators wrote. “Mendelian randomization analyses are less likely to be biased by confounding or reverse causation than observational studies if a set of assumptions are met.”
The approach uncovered a significant association between rs4988235 and Parkinson’s disease, with a 70% increase in disease risk per one serving of dairy per day (odds ratio, 1.70; 95% confidence interval, 1.12-2.60; P = .013). Further analysis revealed that this finding was driven by men, who had a 2.5-fold increased risk of Parkinson’s disease per one serving per day (OR, 2.50; 95% CI, 1.37-4.56; P = .003) versus women, among whom there was no significant association (OR, 1.04; 95% CI, 0.56-1.92; P = .91). No significant associations were observed among individuals grouped by age or Parkinson’s disease duration.
“Our findings suggest that dairy intake increases Parkinson’s disease risk,” the investigators concluded. “Therefore, diets with limited milk intake (e.g., Mediterranean diet) may be beneficial with respect to Parkinson’s disease.”
Further evidence supporting a link between diet and Parkinson’s disease
According to Silke Appel-Cresswell, MD, Marg Meikle Professor for Parkinson’s Research at the University of British Columbia, Vancouver, the findings align with previous prospective cohort studies demonstrating an increased risk of Parkinson’s disease with greater consumption of dairy.
“What the current study adds,” Dr. Appel-Cresswell said, “is a complementary approach to assess the association where the risk of reverse causation and of confounding are minimized. Like in some of the previous studies, the authors find sex differences with an increased risk for men but not women.”
Dr. Appel-Cresswell noted that an increasing body of evidence supports a link between diet and Parkinson’s disease, including a study of her own published last year, which showed later onset of Parkinson’s disease among individuals with a Mediterranean-style diet.
“We are accumulating evidence for a role of diet (or more broadly, the food exposome) for the risk to develop Parkinson’s disease,” Dr. Appel-Cresswell said, noting that “key pieces are still missing, including mechanisms underlying associations, clinical trials in individuals with established Parkinson’s disease and – eventually – preventive interventions. This research is urgently needed and analyses will need to take sex differences and a large range of potential other factors into account.”
A ‘modest’ contributing factor?
Vikas Kotagal, MD, associate professor of neurology at the University of Michigan, Ann Arbor, offered a perspective on the study methodology, and suggested that a causal link between dairy intake and Parkinson’s disease, if present, is likely minimal.
“Limitations to the study include the fact that participants weren’t actually asked or tested for how much dairy they truly consumed,” Dr. Kotagal said*. “Their dairy intake was estimated based on their genetic background – there are certainly many assumptions baked into this analytic approach which may or may not be true. It is also worth noting the fact that this causal association was seen in men and not women, suggesting that even if dairy intake was truly causal, it is likely to be a modest contributing factor and not a significant cause of Parkinson’s disease in the broader population in general.”
Still, Dr. Kotagal agreed with Dr. Appel-Cresswell that underlying mechanisms need further investigation.
“The biggest takeaway here is to heighten the urgency for researchers and funders to explore whether factors that might cluster with dairy intake – including pesticide exposure in milk or even the make-up of bacterial populations in different peoples’ intestines – might deserve closer scrutiny as a missing link connecting dairy consumption to increased Parkinson’s disease risk,” Dr. Kotagal said.
Dietary advice
Considering all available evidence, Dr. Appel-Cresswell offered some dietary advice with benefits that may extend beyond prevention of Parkinson’s disease.
“From a clinical point of view, I suggest to limit dairy intake to a moderate amount,” she said. “Mediterranean diets so far have the best supporting evidence for a lower Parkinson’s disease risk, although data is lacking for benefits in established Parkinson’s disease. Given the low risk of the Mediterranean diet and the established benefits for a host of other medical conditions, this is generally a safe and delicious recommendation whether one is living with Parkinson’s or not.”
The study was supported by the European Union Joint Program for Neurodegenerative Disease Research, the National Centre of Excellence in Research on Parkinson’s Disease, the National Institutes of Health, and others. The investigators disclosed additional relationships with Astellas Pharma, Sanofi, Pfizer, and others. Dr. Kotagal and Dr. Appel-Cresswell reported no relevant conflicts of interest.
*Correction, 2/10/22: An earlier version of this article misstated Dr. Kotagal's name in certain instances, including a photo caption.
according to investigators. Men of European ancestry with a genetic marker predicting dairy consumption had significantly greater risk of Parkinson’s disease than individuals without the marker, suggesting a causal relationship between dairy intake and Parkinson’s disease, lead author Cloé Domenighetti, MSc, a PhD student at UVSQ, Université Paris Sud, and colleagues reported.
“Previous studies highlighted dairy intake as a risk factor of Parkinson’s disease,” the investigators wrote in Movement Disorders. “A meta-analysis of prospective studies reported a 40% increased Parkinson’s disease risk in participants with the highest intake. It is unclear whether the association is causal or explained by confounding or reverse causation, given the long prodromal phase of Parkinson’s disease.”
A Mendelian randomization study
The investigators evaluated this link by comparing 9,823 cases of Parkinson’s disease with 8,376 controls, all individuals of European ancestry from the Courage-Parkinson’s disease consortium, comprising 23 studies. Data were analyzed by two-sample Mendelian randomization, a technique that uses genotype to predict behavior, thereby replacing conventional methods of capturing behavior, such as questionnaires. In this case, the investigators screened all participants for rs4988235, a single-nucleotide polymorphism (SNP) upstream of the lactase gene that is well documented to predict dairy intake among individuals of European ancestry.
“Mendelian randomization uses genetic variants associated with exposures as instrumental variables to estimate causal relationships between exposures and outcomes,” the investigators wrote. “Mendelian randomization analyses are less likely to be biased by confounding or reverse causation than observational studies if a set of assumptions are met.”
The approach uncovered a significant association between rs4988235 and Parkinson’s disease, with a 70% increase in disease risk per one serving of dairy per day (odds ratio, 1.70; 95% confidence interval, 1.12-2.60; P = .013). Further analysis revealed that this finding was driven by men, who had a 2.5-fold increased risk of Parkinson’s disease per one serving per day (OR, 2.50; 95% CI, 1.37-4.56; P = .003) versus women, among whom there was no significant association (OR, 1.04; 95% CI, 0.56-1.92; P = .91). No significant associations were observed among individuals grouped by age or Parkinson’s disease duration.
“Our findings suggest that dairy intake increases Parkinson’s disease risk,” the investigators concluded. “Therefore, diets with limited milk intake (e.g., Mediterranean diet) may be beneficial with respect to Parkinson’s disease.”
Further evidence supporting a link between diet and Parkinson’s disease
According to Silke Appel-Cresswell, MD, Marg Meikle Professor for Parkinson’s Research at the University of British Columbia, Vancouver, the findings align with previous prospective cohort studies demonstrating an increased risk of Parkinson’s disease with greater consumption of dairy.
“What the current study adds,” Dr. Appel-Cresswell said, “is a complementary approach to assess the association where the risk of reverse causation and of confounding are minimized. Like in some of the previous studies, the authors find sex differences with an increased risk for men but not women.”
Dr. Appel-Cresswell noted that an increasing body of evidence supports a link between diet and Parkinson’s disease, including a study of her own published last year, which showed later onset of Parkinson’s disease among individuals with a Mediterranean-style diet.
“We are accumulating evidence for a role of diet (or more broadly, the food exposome) for the risk to develop Parkinson’s disease,” Dr. Appel-Cresswell said, noting that “key pieces are still missing, including mechanisms underlying associations, clinical trials in individuals with established Parkinson’s disease and – eventually – preventive interventions. This research is urgently needed and analyses will need to take sex differences and a large range of potential other factors into account.”
A ‘modest’ contributing factor?
Vikas Kotagal, MD, associate professor of neurology at the University of Michigan, Ann Arbor, offered a perspective on the study methodology, and suggested that a causal link between dairy intake and Parkinson’s disease, if present, is likely minimal.
“Limitations to the study include the fact that participants weren’t actually asked or tested for how much dairy they truly consumed,” Dr. Kotagal said*. “Their dairy intake was estimated based on their genetic background – there are certainly many assumptions baked into this analytic approach which may or may not be true. It is also worth noting the fact that this causal association was seen in men and not women, suggesting that even if dairy intake was truly causal, it is likely to be a modest contributing factor and not a significant cause of Parkinson’s disease in the broader population in general.”
Still, Dr. Kotagal agreed with Dr. Appel-Cresswell that underlying mechanisms need further investigation.
“The biggest takeaway here is to heighten the urgency for researchers and funders to explore whether factors that might cluster with dairy intake – including pesticide exposure in milk or even the make-up of bacterial populations in different peoples’ intestines – might deserve closer scrutiny as a missing link connecting dairy consumption to increased Parkinson’s disease risk,” Dr. Kotagal said.
Dietary advice
Considering all available evidence, Dr. Appel-Cresswell offered some dietary advice with benefits that may extend beyond prevention of Parkinson’s disease.
“From a clinical point of view, I suggest to limit dairy intake to a moderate amount,” she said. “Mediterranean diets so far have the best supporting evidence for a lower Parkinson’s disease risk, although data is lacking for benefits in established Parkinson’s disease. Given the low risk of the Mediterranean diet and the established benefits for a host of other medical conditions, this is generally a safe and delicious recommendation whether one is living with Parkinson’s or not.”
The study was supported by the European Union Joint Program for Neurodegenerative Disease Research, the National Centre of Excellence in Research on Parkinson’s Disease, the National Institutes of Health, and others. The investigators disclosed additional relationships with Astellas Pharma, Sanofi, Pfizer, and others. Dr. Kotagal and Dr. Appel-Cresswell reported no relevant conflicts of interest.
*Correction, 2/10/22: An earlier version of this article misstated Dr. Kotagal's name in certain instances, including a photo caption.
FROM MOVEMENT DISORDERS
Positive phase 3 topline results for early Parkinson’s drug
Topline results from a phase 3 trial of P2B001, a fixed-dose combination of extended release (ER) formulations of pramipexole and rasagiline, showed it was superior to its individual components as a first-line treatment for early Parkinson’s disease.
Study participants also reported less daytime sleepiness with P2B001, according to a statement from the drug’s manufacturer.
while mitigating the side effects typically associated with this class of medicine such as somnolence, orthostatic hypotension, and hallucinations,” Sheila Oren, MD, chief executive officer of Pharma Two B, said in a statement.
“This is important for PD patients of all ages and is critical for the elderly, who typically do not tolerate side effects of dopamine agonists,” Dr. Oren added.
Promising results
The 12-week, international, randomized, double-blind trial was designed to study the efficacy, safety, and tolerability of P2B001 compared to its individual components and to a calibration arm of pramipexole ER in 544 patients with early PD.
Participants received P2B001, a once-daily ER combination product composed of pramipexole 0.6 mg and rasagiline 0.75 mg; pramipexole ER capsule 0.6 mg once daily; rasagiline ER capsule 0.75 mg once daily; or the currently marketed product pramipexole ER capsules titrated to an optimal dose for each individual patient (1.5-4.5 mg).
The adjusted mean change from baseline in total Unified Parkinson’s Disease Rating Scale (UPDRS) score was –2.66 points for P2B001 versus pramipexole (P = .0018) and –3.30 points for P2B001 versus rasagiline (P = .0001). There was no significant difference in UPDRS scores between P2B001 and pramipexole ER.
The adjusted mean change from baseline in the Epworth Sleepiness Scale score for P2B001 versus pramipexole ER was –2.66 points (P < .0001).
Treatment-related adverse events were mostly mild or moderate and were similar among groups.
“The initiation of treatment of patients with Parkinson’s disease represents an area of unmet need due to the side effects associated with current treatments,” Warren Olanow, MD, professor emeritus of neurology and neuroscience at the Icahn School of Medicine at Mount Sinai in New York, said in a statement from the manufacturer.
“Based on the data from this well-designed, rigorous, active-controlled study, P2B001 has the potential to become a leading treatment option for PD, particularly as first line therapy for early-stage patients of all ages,” Dr. Olanow added.
The company plans to file a new drug application in 2022.
A version of this article first appeared on Medscape.com.
Topline results from a phase 3 trial of P2B001, a fixed-dose combination of extended release (ER) formulations of pramipexole and rasagiline, showed it was superior to its individual components as a first-line treatment for early Parkinson’s disease.
Study participants also reported less daytime sleepiness with P2B001, according to a statement from the drug’s manufacturer.
while mitigating the side effects typically associated with this class of medicine such as somnolence, orthostatic hypotension, and hallucinations,” Sheila Oren, MD, chief executive officer of Pharma Two B, said in a statement.
“This is important for PD patients of all ages and is critical for the elderly, who typically do not tolerate side effects of dopamine agonists,” Dr. Oren added.
Promising results
The 12-week, international, randomized, double-blind trial was designed to study the efficacy, safety, and tolerability of P2B001 compared to its individual components and to a calibration arm of pramipexole ER in 544 patients with early PD.
Participants received P2B001, a once-daily ER combination product composed of pramipexole 0.6 mg and rasagiline 0.75 mg; pramipexole ER capsule 0.6 mg once daily; rasagiline ER capsule 0.75 mg once daily; or the currently marketed product pramipexole ER capsules titrated to an optimal dose for each individual patient (1.5-4.5 mg).
The adjusted mean change from baseline in total Unified Parkinson’s Disease Rating Scale (UPDRS) score was –2.66 points for P2B001 versus pramipexole (P = .0018) and –3.30 points for P2B001 versus rasagiline (P = .0001). There was no significant difference in UPDRS scores between P2B001 and pramipexole ER.
The adjusted mean change from baseline in the Epworth Sleepiness Scale score for P2B001 versus pramipexole ER was –2.66 points (P < .0001).
Treatment-related adverse events were mostly mild or moderate and were similar among groups.
“The initiation of treatment of patients with Parkinson’s disease represents an area of unmet need due to the side effects associated with current treatments,” Warren Olanow, MD, professor emeritus of neurology and neuroscience at the Icahn School of Medicine at Mount Sinai in New York, said in a statement from the manufacturer.
“Based on the data from this well-designed, rigorous, active-controlled study, P2B001 has the potential to become a leading treatment option for PD, particularly as first line therapy for early-stage patients of all ages,” Dr. Olanow added.
The company plans to file a new drug application in 2022.
A version of this article first appeared on Medscape.com.
Topline results from a phase 3 trial of P2B001, a fixed-dose combination of extended release (ER) formulations of pramipexole and rasagiline, showed it was superior to its individual components as a first-line treatment for early Parkinson’s disease.
Study participants also reported less daytime sleepiness with P2B001, according to a statement from the drug’s manufacturer.
while mitigating the side effects typically associated with this class of medicine such as somnolence, orthostatic hypotension, and hallucinations,” Sheila Oren, MD, chief executive officer of Pharma Two B, said in a statement.
“This is important for PD patients of all ages and is critical for the elderly, who typically do not tolerate side effects of dopamine agonists,” Dr. Oren added.
Promising results
The 12-week, international, randomized, double-blind trial was designed to study the efficacy, safety, and tolerability of P2B001 compared to its individual components and to a calibration arm of pramipexole ER in 544 patients with early PD.
Participants received P2B001, a once-daily ER combination product composed of pramipexole 0.6 mg and rasagiline 0.75 mg; pramipexole ER capsule 0.6 mg once daily; rasagiline ER capsule 0.75 mg once daily; or the currently marketed product pramipexole ER capsules titrated to an optimal dose for each individual patient (1.5-4.5 mg).
The adjusted mean change from baseline in total Unified Parkinson’s Disease Rating Scale (UPDRS) score was –2.66 points for P2B001 versus pramipexole (P = .0018) and –3.30 points for P2B001 versus rasagiline (P = .0001). There was no significant difference in UPDRS scores between P2B001 and pramipexole ER.
The adjusted mean change from baseline in the Epworth Sleepiness Scale score for P2B001 versus pramipexole ER was –2.66 points (P < .0001).
Treatment-related adverse events were mostly mild or moderate and were similar among groups.
“The initiation of treatment of patients with Parkinson’s disease represents an area of unmet need due to the side effects associated with current treatments,” Warren Olanow, MD, professor emeritus of neurology and neuroscience at the Icahn School of Medicine at Mount Sinai in New York, said in a statement from the manufacturer.
“Based on the data from this well-designed, rigorous, active-controlled study, P2B001 has the potential to become a leading treatment option for PD, particularly as first line therapy for early-stage patients of all ages,” Dr. Olanow added.
The company plans to file a new drug application in 2022.
A version of this article first appeared on Medscape.com.
Diabetes tied to Parkinson’s risk, more rapid disease progression
Diabetes mellitus (DM) is associated with Parkinson’s disease (PD) development, as well as more severe symptoms and more rapid disease progression, new research suggests.
In a systematic review, patients with type 2 diabetes were 34% more likely to develop PD than those without comorbid DM. In addition, patients with both conditions had significantly worse scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) and worse cognitive performance.
Together, the results suggest that “DM may be a facilitating factor of neurodegeneration,” wrote the investigators, led by Gennaro Pagano, MD, PhD, expert medical director at Roche Pharma Research and Early Development, in Basel, Switzerland.
The findings were published in a recent issue of the Journal of Parkinson’s Disease.
Unanswered questions
Researchers have long proposed a potential relationship between diabetes and PD. However, case-control studies have yielded conflicting results about this relationship – and previous systematic reviews have failed to clarify the question.
In the current systematic review and meta-analysis, investigators identified relevant studies in databases such as MEDLINE/PubMed, Cochrane CENTRAL, and Scopus.
Eligible studies reported prevalence of DM in patients with PD, reported incidence of PD in those with and those without DM, and analyzed Parkinson’s phenotype and progression in those with and those without DM.
The researchers identified 3,829 articles in their initial search, evaluated 90 articles in detail, and included 43 studies in their analysis. Study quality was judged to be moderate or good, and the investigators did not find significant publication bias.
Twenty-one studies that encompassed 11,396 patients were examined to determine prevalence of DM in PD. This prevalence was calculated to be 10.02%, which is similar to the global prevalence of 9.3% reported in 2019.
The researchers also analyzed 12 cohort studies that included 17,797,221 patients to calculate risk for PD in patients with comorbid diabetes. The pooled summary odds ratio for incident PD among patients with type 2 diabetes was 1.34.
The evaluation of the effect of diabetes on PD severity was based on 10 studies that included 603 patients with both diseases. Because data on motor symptoms were not available for all studies, the researchers considered Hoehn and Yahr stage, UPDRS score, and cognitive impairment.
Patients with both conditions had a worse Hoehn and Yahr stage (standardized mean difference, 0.36; P < .001), and higher UPDRS score (SMD, 0.60; P < .001). In 7 of the 10 studies, diabetes was associated with worse cognitive performance in patients with PD.
Mechanisms uncertain
The mechanisms of the effect of diabetes on risk for and severity of PD are uncertain, but the researchers have developed hypotheses.
“Overlapping mechanisms between insulin resistance, mitochondrial dysfunction, oxidative stress, and alpha-synuclein expression could influence the development of the neurodegeneration process,” they wrote.
Because the current analysis demonstrated a trend toward more pronounced cognitive decline in patients with the comorbidities, clinicians should pay particular attention to the progression of motor and cognitive symptoms in patients with these diseases, the investigators noted.
“Additional studies are needed in order to better define the clinical phenotype of PD-DM patients and explore the role of antidiabetic drugs on PD progression,” they wrote.
They add that future studies also are needed to evaluate whether antidiabetic drugs might reduce risk for PD in these patients.
The investigators noted several limitations of their research. In many of the studies they examined, for example, diagnostic criteria of type 2 diabetes and PD were based only on medical records or self-reported health questionnaires. The diagnoses were rarely confirmed.
In addition, not all studies clearly stated that their populations presented with type 2 diabetes. Finally, patients with diabetes may be at increased risk for cardiovascular death, which could affect follow-up related to the development of PD, the investigators noted.
A version of this article first appeared on Medscape.com.
Diabetes mellitus (DM) is associated with Parkinson’s disease (PD) development, as well as more severe symptoms and more rapid disease progression, new research suggests.
In a systematic review, patients with type 2 diabetes were 34% more likely to develop PD than those without comorbid DM. In addition, patients with both conditions had significantly worse scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) and worse cognitive performance.
Together, the results suggest that “DM may be a facilitating factor of neurodegeneration,” wrote the investigators, led by Gennaro Pagano, MD, PhD, expert medical director at Roche Pharma Research and Early Development, in Basel, Switzerland.
The findings were published in a recent issue of the Journal of Parkinson’s Disease.
Unanswered questions
Researchers have long proposed a potential relationship between diabetes and PD. However, case-control studies have yielded conflicting results about this relationship – and previous systematic reviews have failed to clarify the question.
In the current systematic review and meta-analysis, investigators identified relevant studies in databases such as MEDLINE/PubMed, Cochrane CENTRAL, and Scopus.
Eligible studies reported prevalence of DM in patients with PD, reported incidence of PD in those with and those without DM, and analyzed Parkinson’s phenotype and progression in those with and those without DM.
The researchers identified 3,829 articles in their initial search, evaluated 90 articles in detail, and included 43 studies in their analysis. Study quality was judged to be moderate or good, and the investigators did not find significant publication bias.
Twenty-one studies that encompassed 11,396 patients were examined to determine prevalence of DM in PD. This prevalence was calculated to be 10.02%, which is similar to the global prevalence of 9.3% reported in 2019.
The researchers also analyzed 12 cohort studies that included 17,797,221 patients to calculate risk for PD in patients with comorbid diabetes. The pooled summary odds ratio for incident PD among patients with type 2 diabetes was 1.34.
The evaluation of the effect of diabetes on PD severity was based on 10 studies that included 603 patients with both diseases. Because data on motor symptoms were not available for all studies, the researchers considered Hoehn and Yahr stage, UPDRS score, and cognitive impairment.
Patients with both conditions had a worse Hoehn and Yahr stage (standardized mean difference, 0.36; P < .001), and higher UPDRS score (SMD, 0.60; P < .001). In 7 of the 10 studies, diabetes was associated with worse cognitive performance in patients with PD.
Mechanisms uncertain
The mechanisms of the effect of diabetes on risk for and severity of PD are uncertain, but the researchers have developed hypotheses.
“Overlapping mechanisms between insulin resistance, mitochondrial dysfunction, oxidative stress, and alpha-synuclein expression could influence the development of the neurodegeneration process,” they wrote.
Because the current analysis demonstrated a trend toward more pronounced cognitive decline in patients with the comorbidities, clinicians should pay particular attention to the progression of motor and cognitive symptoms in patients with these diseases, the investigators noted.
“Additional studies are needed in order to better define the clinical phenotype of PD-DM patients and explore the role of antidiabetic drugs on PD progression,” they wrote.
They add that future studies also are needed to evaluate whether antidiabetic drugs might reduce risk for PD in these patients.
The investigators noted several limitations of their research. In many of the studies they examined, for example, diagnostic criteria of type 2 diabetes and PD were based only on medical records or self-reported health questionnaires. The diagnoses were rarely confirmed.
In addition, not all studies clearly stated that their populations presented with type 2 diabetes. Finally, patients with diabetes may be at increased risk for cardiovascular death, which could affect follow-up related to the development of PD, the investigators noted.
A version of this article first appeared on Medscape.com.
Diabetes mellitus (DM) is associated with Parkinson’s disease (PD) development, as well as more severe symptoms and more rapid disease progression, new research suggests.
In a systematic review, patients with type 2 diabetes were 34% more likely to develop PD than those without comorbid DM. In addition, patients with both conditions had significantly worse scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) and worse cognitive performance.
Together, the results suggest that “DM may be a facilitating factor of neurodegeneration,” wrote the investigators, led by Gennaro Pagano, MD, PhD, expert medical director at Roche Pharma Research and Early Development, in Basel, Switzerland.
The findings were published in a recent issue of the Journal of Parkinson’s Disease.
Unanswered questions
Researchers have long proposed a potential relationship between diabetes and PD. However, case-control studies have yielded conflicting results about this relationship – and previous systematic reviews have failed to clarify the question.
In the current systematic review and meta-analysis, investigators identified relevant studies in databases such as MEDLINE/PubMed, Cochrane CENTRAL, and Scopus.
Eligible studies reported prevalence of DM in patients with PD, reported incidence of PD in those with and those without DM, and analyzed Parkinson’s phenotype and progression in those with and those without DM.
The researchers identified 3,829 articles in their initial search, evaluated 90 articles in detail, and included 43 studies in their analysis. Study quality was judged to be moderate or good, and the investigators did not find significant publication bias.
Twenty-one studies that encompassed 11,396 patients were examined to determine prevalence of DM in PD. This prevalence was calculated to be 10.02%, which is similar to the global prevalence of 9.3% reported in 2019.
The researchers also analyzed 12 cohort studies that included 17,797,221 patients to calculate risk for PD in patients with comorbid diabetes. The pooled summary odds ratio for incident PD among patients with type 2 diabetes was 1.34.
The evaluation of the effect of diabetes on PD severity was based on 10 studies that included 603 patients with both diseases. Because data on motor symptoms were not available for all studies, the researchers considered Hoehn and Yahr stage, UPDRS score, and cognitive impairment.
Patients with both conditions had a worse Hoehn and Yahr stage (standardized mean difference, 0.36; P < .001), and higher UPDRS score (SMD, 0.60; P < .001). In 7 of the 10 studies, diabetes was associated with worse cognitive performance in patients with PD.
Mechanisms uncertain
The mechanisms of the effect of diabetes on risk for and severity of PD are uncertain, but the researchers have developed hypotheses.
“Overlapping mechanisms between insulin resistance, mitochondrial dysfunction, oxidative stress, and alpha-synuclein expression could influence the development of the neurodegeneration process,” they wrote.
Because the current analysis demonstrated a trend toward more pronounced cognitive decline in patients with the comorbidities, clinicians should pay particular attention to the progression of motor and cognitive symptoms in patients with these diseases, the investigators noted.
“Additional studies are needed in order to better define the clinical phenotype of PD-DM patients and explore the role of antidiabetic drugs on PD progression,” they wrote.
They add that future studies also are needed to evaluate whether antidiabetic drugs might reduce risk for PD in these patients.
The investigators noted several limitations of their research. In many of the studies they examined, for example, diagnostic criteria of type 2 diabetes and PD were based only on medical records or self-reported health questionnaires. The diagnoses were rarely confirmed.
In addition, not all studies clearly stated that their populations presented with type 2 diabetes. Finally, patients with diabetes may be at increased risk for cardiovascular death, which could affect follow-up related to the development of PD, the investigators noted.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF PARKINSON’S DISEASE