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Food as Medicine: Diet’s Role in Parkinson’s Disease
For 15 years, John Duda, MD, national director of the VA Parkinson’s Disease Research, Education and Clinical Centers, has urged his patients to “keep waiting” for effective treatments to manage both motor and nonmotor symptoms of Parkinson’s disease.
However, Duda, who also serves as director of the Brain Wellness Clinic at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, Pennsylvania, recognized the persistent lack of effective drugs to address these symptoms. This prompted him to consider what other evidence-based strategies he could use to support his patients.
“I recognized that nutritional approaches within a broader program that includes medication review, stress management, social connections, adequate sleep, and physical exercise could make a real difference,” he said.
Observational studies have shown an inverse association between dietary patterns and Parkinson’s disease risk, age of onset, symptom severity, and mortality rates — particularly with the Mediterranean diet (MeDi) and the MIND diet, which combines elements of MeDi and the Dietary Approaches to Stop Hypertension (DASH) diet. Although randomized controlled trials are still limited, the epidemiologic evidence supporting dietary interventions is “compelling,” said Duda.
For example, a cross-sectional study comparing 167 participants with Parkinson’s disease vs 119 controls showed that later age of Parkinson’s disease onset correlated with adherence to the MIND diet in women, with a difference of up to 17.4 years (P < .001) between low and high dietary tertiles.
The MeDi was correlated with later onset in men, with differences of up to 8.4 years (P = .002). As previously reported, a healthy diet emphasizing vegetables, fruits, nuts, and grains was inversely associated with prodromal features of Parkinson’s disease, including constipation, excessive daytime sleepiness, and depression. In addition, lower rates of Parkinson’s disease have been shown in populations following vegetarian and vegan dietary patterns.
Does Parkinson’s disease Start in the Gut?
Parkinson’s disease is characterized by decreased short-chain fatty acid–producing bacteria and increased pro-inflammatory species linked to intestinal inflammation and alpha-synuclein aggregation. “There are reasons to believe that a-synuclein accumulation may start in the gut,” Duda noted.
Numerous studies implicate gut microbiome dysbiosis as a pathogenic mechanism in Parkinson’s disease, with gastrointestinal symptoms often predating motor symptoms. Dysbiosis might result in a pro-inflammatory state potentially linked to the recurrent gastrointestinal symptoms. Fecal microbiota transplant may restore a healthier gut environment and beneficially affect Parkinson’s disease symptoms, he said.
Some of the benefits conferred by the MeDi and other healthy diets may be mediated by improving the gut microbiome. Duda cited a study that showed that a 14-day ovo-lacto vegetarian diet intervention and a daily fecal enema for 8 days improved not only the microbiome but also Movement Disorder Society Unified Parkinson’s Disease Rating Scale—part III scores.
Duda also reviewed the role of dietary interventions in addressing common Parkinson’s disease symptoms, such as orthostatic hypotension. He recommended that Parkinson’s disease patients with this condition should avoid eating large meals, increase dietary salt intake, increase fluid intake, and decrease alcohol intake.
Malnutrition affects close to 25% of those with Parkinson’s disease, which is partially attributable to diminished olfaction. Because the experience of taste is largely driven by a sense of smell, patients may be less interested in eating. Duda recommended increasing herbs, spices, and other flavors in food. High caloric–density foods, including nuts, nut butters, and seeds, can boost weight, he said. However, he added, any patient with significant weight loss should consult a nutritionist.
Constipation is one of the most debilitating symptoms of Parkinson’s disease, affecting up to 66% of patients. Duda advised increasing fluid intake, exercise, and dietary fiber and use of stool softeners and laxatives. The MeDi may reduce symptoms of constipation and have a beneficial effect on gut microbiota.
Coffee may be helpful for sleepiness in Parkinson’s disease and may also confer neuroprotective, motor, and cognitive benefits. As an adjuvant treatment, caffeine may alter levodopa pharmacokinetics, reduce dyskinesia, improve gait in patients with freezing and may even reduce the risk of developing Parkinson’s disease, with a maximum benefit reached at approximately three cups of coffee daily.
Problematic Foods
There is also a growing body of evidence regarding the deleterious effects of ultraprocessed foods (UPFs), Duda said. He noted that a recent systematic review and meta-analysis of 28 studies showed that higher UPF intake was significantly associated with an enhanced risk for Parkinson’s disease (relative risk, 1.56; 95% CI, 1.21-2.02). As previously reported, UPFs have been tied to a host of adverse neurologic outcomes, including cognitive decline and stroke.
Although protein is a necessary nutrient, incorporating it into the diet of Parkinson’s disease patients taking levodopa is complicated. Levodopa, a large neutral amino acid (LNAA), competes with other LNAAs for transport to the brain from the small intestine, Duda explained.
“Some people notice that carbidopa-levodopa doesn’t work as well if taken with a high-protein meal.” He recommended taking carbidopa-levodopa 30 minutes before or 60 minutes after meals.
Rebecca Gilbert, MD, PhD, chief mission officer of the American Parkinson’s Disease Association, said that patients with Parkinson’s disease might want to avoid eating protein during the day, concentrating instead on carbohydrates and vegetables and saving the protein for the evening, which is closer to bedtime. Some evidence also supports the use of protein redistribution diets to enhance the clinical response to levodopa and reduce motor fluctuations.
What About Supplements?
It’s “hard to prove that one specific supplement can be protective against Parkinson’s disease because diet consists of many different components and the whole diet may be worth more than the sum of its parts,” Gilbert said. The evidence for individual supplements “isn’t robust enough to say they prevent or treat Parkinson’s disease.”
Research on the role of specific nutrients in Parkinson’s disease is conflicting, with no clear evidence supporting or refuting their benefits. For example, a study that followed participants for about 30 years showed no link between reduced Parkinson’s disease risk and vitamin B or folate intake.
On the other hand, there is research suggesting that certain vitamins may help reduce Parkinson’s disease risk, although these nutrients do not operate in isolation. For instance, one recent study showed a connection between vitamins C and E and reduced Parkinson’s disease risk, but factors such as body mass index and coffee consumption appeared to influence the strength of this association.
Consuming polyunsaturated fatty acids along with reducing saturated fatty acid intake has been tied to a reduced risk for Parkinson’s disease.
Additionally, certain foods may offer protective effects, including green and black tea, with consumption of three or more cups per day associated with a delay in motor symptom onset by 7.7 years. Foods high in nicotine content, such as those from the Solanaceae family — including peppers, tomatoes, tomato juice, and potatoes — have also been linked to potential protective benefits.
Diets rich in antioxidants, including carotenoids, lutein, and vitamins E and C, have been robustly linked to a reduced risk for parkinsonism and progression of parkinsonian symptoms in older adults.
Increasing the intake of dietary flavonoids, particularly tea, berry fruits, apples, red wine, and oranges or orange juice, can reduce Parkinson’s disease risk. One study showed that male participants in the highest quintile of total flavonoid consumption had a 40% lower Parkinson’s disease risk compared with those in the lowest quintile. Another study showed that flavonoid-rich foods were also associated with a lower risk for death in patients with Parkinson’s disease.
Food as Medicine
Although recent research shows that the drug development pipeline for Parkinson’s disease is robust, with a wide variety of approaches being developed and evaluated in phase 1 and 2, investigators note that only a limited number of disease-modifying treatments are transitioning to phase 3.
Duda noted that phytochemicals incorporated into the diet might target some of the same mechanisms that are targets of these drugs in development.
“Flavonoids have been shown to stabilize alpha-synuclein in vitro,” he said. “Caffeine, curcumin, resveratrol, and eliminating meat and dairy inhibit mTOR [mammalian target of rapamycin], and mTOR inhibition results in increased autophagy that may help clear alpha-synuclein. Genestein, an isoflavone in soybeans, protects dopaminergic neurons by inhibiting microglia activation. Flavonoids inhibit inflammation by inhibiting release of NO [nitric oxide] and pro-inflammatory cytokines,” he noted.
Ongoing studies of dietary interventions for Parkinson’s disease are exploring various areas, including the potential role of the ketogenic diet in protecting the gut microbiome, optimizing protein intake for muscle preservation and sleep, the effects of psyllium and wheat bran on weight and constipation, and the impact of a gluten-free diet.
Practical Tips for Healthy Eating
Gilbert emphasized that there are no medications or interventions currently available that can delay a Parkinson’s disease diagnosis by up to 17 years, as some dietary patterns have been shown to do, and she noted that it’s not possible to replicate the MeDi diet in a pill. However, she recommended a practical approach to eating that includes a diet low in ultraprocessed foods and high in beneficial nutrients. She encouraged people to shop for “real food” and enjoy a variety of colorful fruits and vegetables.
Duda acknowledged that motivating patients to follow a healthy diet can be difficult. As a result, the focus often shifts to making small adjustments and modifications. For example, he suggested that instead of pairing meat with French fries, people could opt for vegetables or add greens to their meals. Similarly, instead of having eggs and bacon for breakfast, they might choose oatmeal.
Preparing whole-food, plant-based meals may take more time than patients are accustomed to, so Duda suggests that, if possible, patients involve loved ones in both the meal preparation and the meal itself. He explained that a healthy meal can become an opportunity for bonding and that the key is educating them about new meal-related concepts.
Duda reported no relevant financial relationships with the pharmaceutical or food industries. He has received compensation from the Physicians Committee for Responsible Medicine for his lecture delivered at the conference and research grant support from the VA, the National Institutes of Health, the Michael J. Fox Foundation, and the Department of Defense unrelated to this topic. Gilbert reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
For 15 years, John Duda, MD, national director of the VA Parkinson’s Disease Research, Education and Clinical Centers, has urged his patients to “keep waiting” for effective treatments to manage both motor and nonmotor symptoms of Parkinson’s disease.
However, Duda, who also serves as director of the Brain Wellness Clinic at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, Pennsylvania, recognized the persistent lack of effective drugs to address these symptoms. This prompted him to consider what other evidence-based strategies he could use to support his patients.
“I recognized that nutritional approaches within a broader program that includes medication review, stress management, social connections, adequate sleep, and physical exercise could make a real difference,” he said.
Observational studies have shown an inverse association between dietary patterns and Parkinson’s disease risk, age of onset, symptom severity, and mortality rates — particularly with the Mediterranean diet (MeDi) and the MIND diet, which combines elements of MeDi and the Dietary Approaches to Stop Hypertension (DASH) diet. Although randomized controlled trials are still limited, the epidemiologic evidence supporting dietary interventions is “compelling,” said Duda.
For example, a cross-sectional study comparing 167 participants with Parkinson’s disease vs 119 controls showed that later age of Parkinson’s disease onset correlated with adherence to the MIND diet in women, with a difference of up to 17.4 years (P < .001) between low and high dietary tertiles.
The MeDi was correlated with later onset in men, with differences of up to 8.4 years (P = .002). As previously reported, a healthy diet emphasizing vegetables, fruits, nuts, and grains was inversely associated with prodromal features of Parkinson’s disease, including constipation, excessive daytime sleepiness, and depression. In addition, lower rates of Parkinson’s disease have been shown in populations following vegetarian and vegan dietary patterns.
Does Parkinson’s disease Start in the Gut?
Parkinson’s disease is characterized by decreased short-chain fatty acid–producing bacteria and increased pro-inflammatory species linked to intestinal inflammation and alpha-synuclein aggregation. “There are reasons to believe that a-synuclein accumulation may start in the gut,” Duda noted.
Numerous studies implicate gut microbiome dysbiosis as a pathogenic mechanism in Parkinson’s disease, with gastrointestinal symptoms often predating motor symptoms. Dysbiosis might result in a pro-inflammatory state potentially linked to the recurrent gastrointestinal symptoms. Fecal microbiota transplant may restore a healthier gut environment and beneficially affect Parkinson’s disease symptoms, he said.
Some of the benefits conferred by the MeDi and other healthy diets may be mediated by improving the gut microbiome. Duda cited a study that showed that a 14-day ovo-lacto vegetarian diet intervention and a daily fecal enema for 8 days improved not only the microbiome but also Movement Disorder Society Unified Parkinson’s Disease Rating Scale—part III scores.
Duda also reviewed the role of dietary interventions in addressing common Parkinson’s disease symptoms, such as orthostatic hypotension. He recommended that Parkinson’s disease patients with this condition should avoid eating large meals, increase dietary salt intake, increase fluid intake, and decrease alcohol intake.
Malnutrition affects close to 25% of those with Parkinson’s disease, which is partially attributable to diminished olfaction. Because the experience of taste is largely driven by a sense of smell, patients may be less interested in eating. Duda recommended increasing herbs, spices, and other flavors in food. High caloric–density foods, including nuts, nut butters, and seeds, can boost weight, he said. However, he added, any patient with significant weight loss should consult a nutritionist.
Constipation is one of the most debilitating symptoms of Parkinson’s disease, affecting up to 66% of patients. Duda advised increasing fluid intake, exercise, and dietary fiber and use of stool softeners and laxatives. The MeDi may reduce symptoms of constipation and have a beneficial effect on gut microbiota.
Coffee may be helpful for sleepiness in Parkinson’s disease and may also confer neuroprotective, motor, and cognitive benefits. As an adjuvant treatment, caffeine may alter levodopa pharmacokinetics, reduce dyskinesia, improve gait in patients with freezing and may even reduce the risk of developing Parkinson’s disease, with a maximum benefit reached at approximately three cups of coffee daily.
Problematic Foods
There is also a growing body of evidence regarding the deleterious effects of ultraprocessed foods (UPFs), Duda said. He noted that a recent systematic review and meta-analysis of 28 studies showed that higher UPF intake was significantly associated with an enhanced risk for Parkinson’s disease (relative risk, 1.56; 95% CI, 1.21-2.02). As previously reported, UPFs have been tied to a host of adverse neurologic outcomes, including cognitive decline and stroke.
Although protein is a necessary nutrient, incorporating it into the diet of Parkinson’s disease patients taking levodopa is complicated. Levodopa, a large neutral amino acid (LNAA), competes with other LNAAs for transport to the brain from the small intestine, Duda explained.
“Some people notice that carbidopa-levodopa doesn’t work as well if taken with a high-protein meal.” He recommended taking carbidopa-levodopa 30 minutes before or 60 minutes after meals.
Rebecca Gilbert, MD, PhD, chief mission officer of the American Parkinson’s Disease Association, said that patients with Parkinson’s disease might want to avoid eating protein during the day, concentrating instead on carbohydrates and vegetables and saving the protein for the evening, which is closer to bedtime. Some evidence also supports the use of protein redistribution diets to enhance the clinical response to levodopa and reduce motor fluctuations.
What About Supplements?
It’s “hard to prove that one specific supplement can be protective against Parkinson’s disease because diet consists of many different components and the whole diet may be worth more than the sum of its parts,” Gilbert said. The evidence for individual supplements “isn’t robust enough to say they prevent or treat Parkinson’s disease.”
Research on the role of specific nutrients in Parkinson’s disease is conflicting, with no clear evidence supporting or refuting their benefits. For example, a study that followed participants for about 30 years showed no link between reduced Parkinson’s disease risk and vitamin B or folate intake.
On the other hand, there is research suggesting that certain vitamins may help reduce Parkinson’s disease risk, although these nutrients do not operate in isolation. For instance, one recent study showed a connection between vitamins C and E and reduced Parkinson’s disease risk, but factors such as body mass index and coffee consumption appeared to influence the strength of this association.
Consuming polyunsaturated fatty acids along with reducing saturated fatty acid intake has been tied to a reduced risk for Parkinson’s disease.
Additionally, certain foods may offer protective effects, including green and black tea, with consumption of three or more cups per day associated with a delay in motor symptom onset by 7.7 years. Foods high in nicotine content, such as those from the Solanaceae family — including peppers, tomatoes, tomato juice, and potatoes — have also been linked to potential protective benefits.
Diets rich in antioxidants, including carotenoids, lutein, and vitamins E and C, have been robustly linked to a reduced risk for parkinsonism and progression of parkinsonian symptoms in older adults.
Increasing the intake of dietary flavonoids, particularly tea, berry fruits, apples, red wine, and oranges or orange juice, can reduce Parkinson’s disease risk. One study showed that male participants in the highest quintile of total flavonoid consumption had a 40% lower Parkinson’s disease risk compared with those in the lowest quintile. Another study showed that flavonoid-rich foods were also associated with a lower risk for death in patients with Parkinson’s disease.
Food as Medicine
Although recent research shows that the drug development pipeline for Parkinson’s disease is robust, with a wide variety of approaches being developed and evaluated in phase 1 and 2, investigators note that only a limited number of disease-modifying treatments are transitioning to phase 3.
Duda noted that phytochemicals incorporated into the diet might target some of the same mechanisms that are targets of these drugs in development.
“Flavonoids have been shown to stabilize alpha-synuclein in vitro,” he said. “Caffeine, curcumin, resveratrol, and eliminating meat and dairy inhibit mTOR [mammalian target of rapamycin], and mTOR inhibition results in increased autophagy that may help clear alpha-synuclein. Genestein, an isoflavone in soybeans, protects dopaminergic neurons by inhibiting microglia activation. Flavonoids inhibit inflammation by inhibiting release of NO [nitric oxide] and pro-inflammatory cytokines,” he noted.
Ongoing studies of dietary interventions for Parkinson’s disease are exploring various areas, including the potential role of the ketogenic diet in protecting the gut microbiome, optimizing protein intake for muscle preservation and sleep, the effects of psyllium and wheat bran on weight and constipation, and the impact of a gluten-free diet.
Practical Tips for Healthy Eating
Gilbert emphasized that there are no medications or interventions currently available that can delay a Parkinson’s disease diagnosis by up to 17 years, as some dietary patterns have been shown to do, and she noted that it’s not possible to replicate the MeDi diet in a pill. However, she recommended a practical approach to eating that includes a diet low in ultraprocessed foods and high in beneficial nutrients. She encouraged people to shop for “real food” and enjoy a variety of colorful fruits and vegetables.
Duda acknowledged that motivating patients to follow a healthy diet can be difficult. As a result, the focus often shifts to making small adjustments and modifications. For example, he suggested that instead of pairing meat with French fries, people could opt for vegetables or add greens to their meals. Similarly, instead of having eggs and bacon for breakfast, they might choose oatmeal.
Preparing whole-food, plant-based meals may take more time than patients are accustomed to, so Duda suggests that, if possible, patients involve loved ones in both the meal preparation and the meal itself. He explained that a healthy meal can become an opportunity for bonding and that the key is educating them about new meal-related concepts.
Duda reported no relevant financial relationships with the pharmaceutical or food industries. He has received compensation from the Physicians Committee for Responsible Medicine for his lecture delivered at the conference and research grant support from the VA, the National Institutes of Health, the Michael J. Fox Foundation, and the Department of Defense unrelated to this topic. Gilbert reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
For 15 years, John Duda, MD, national director of the VA Parkinson’s Disease Research, Education and Clinical Centers, has urged his patients to “keep waiting” for effective treatments to manage both motor and nonmotor symptoms of Parkinson’s disease.
However, Duda, who also serves as director of the Brain Wellness Clinic at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, Pennsylvania, recognized the persistent lack of effective drugs to address these symptoms. This prompted him to consider what other evidence-based strategies he could use to support his patients.
“I recognized that nutritional approaches within a broader program that includes medication review, stress management, social connections, adequate sleep, and physical exercise could make a real difference,” he said.
Observational studies have shown an inverse association between dietary patterns and Parkinson’s disease risk, age of onset, symptom severity, and mortality rates — particularly with the Mediterranean diet (MeDi) and the MIND diet, which combines elements of MeDi and the Dietary Approaches to Stop Hypertension (DASH) diet. Although randomized controlled trials are still limited, the epidemiologic evidence supporting dietary interventions is “compelling,” said Duda.
For example, a cross-sectional study comparing 167 participants with Parkinson’s disease vs 119 controls showed that later age of Parkinson’s disease onset correlated with adherence to the MIND diet in women, with a difference of up to 17.4 years (P < .001) between low and high dietary tertiles.
The MeDi was correlated with later onset in men, with differences of up to 8.4 years (P = .002). As previously reported, a healthy diet emphasizing vegetables, fruits, nuts, and grains was inversely associated with prodromal features of Parkinson’s disease, including constipation, excessive daytime sleepiness, and depression. In addition, lower rates of Parkinson’s disease have been shown in populations following vegetarian and vegan dietary patterns.
Does Parkinson’s disease Start in the Gut?
Parkinson’s disease is characterized by decreased short-chain fatty acid–producing bacteria and increased pro-inflammatory species linked to intestinal inflammation and alpha-synuclein aggregation. “There are reasons to believe that a-synuclein accumulation may start in the gut,” Duda noted.
Numerous studies implicate gut microbiome dysbiosis as a pathogenic mechanism in Parkinson’s disease, with gastrointestinal symptoms often predating motor symptoms. Dysbiosis might result in a pro-inflammatory state potentially linked to the recurrent gastrointestinal symptoms. Fecal microbiota transplant may restore a healthier gut environment and beneficially affect Parkinson’s disease symptoms, he said.
Some of the benefits conferred by the MeDi and other healthy diets may be mediated by improving the gut microbiome. Duda cited a study that showed that a 14-day ovo-lacto vegetarian diet intervention and a daily fecal enema for 8 days improved not only the microbiome but also Movement Disorder Society Unified Parkinson’s Disease Rating Scale—part III scores.
Duda also reviewed the role of dietary interventions in addressing common Parkinson’s disease symptoms, such as orthostatic hypotension. He recommended that Parkinson’s disease patients with this condition should avoid eating large meals, increase dietary salt intake, increase fluid intake, and decrease alcohol intake.
Malnutrition affects close to 25% of those with Parkinson’s disease, which is partially attributable to diminished olfaction. Because the experience of taste is largely driven by a sense of smell, patients may be less interested in eating. Duda recommended increasing herbs, spices, and other flavors in food. High caloric–density foods, including nuts, nut butters, and seeds, can boost weight, he said. However, he added, any patient with significant weight loss should consult a nutritionist.
Constipation is one of the most debilitating symptoms of Parkinson’s disease, affecting up to 66% of patients. Duda advised increasing fluid intake, exercise, and dietary fiber and use of stool softeners and laxatives. The MeDi may reduce symptoms of constipation and have a beneficial effect on gut microbiota.
Coffee may be helpful for sleepiness in Parkinson’s disease and may also confer neuroprotective, motor, and cognitive benefits. As an adjuvant treatment, caffeine may alter levodopa pharmacokinetics, reduce dyskinesia, improve gait in patients with freezing and may even reduce the risk of developing Parkinson’s disease, with a maximum benefit reached at approximately three cups of coffee daily.
Problematic Foods
There is also a growing body of evidence regarding the deleterious effects of ultraprocessed foods (UPFs), Duda said. He noted that a recent systematic review and meta-analysis of 28 studies showed that higher UPF intake was significantly associated with an enhanced risk for Parkinson’s disease (relative risk, 1.56; 95% CI, 1.21-2.02). As previously reported, UPFs have been tied to a host of adverse neurologic outcomes, including cognitive decline and stroke.
Although protein is a necessary nutrient, incorporating it into the diet of Parkinson’s disease patients taking levodopa is complicated. Levodopa, a large neutral amino acid (LNAA), competes with other LNAAs for transport to the brain from the small intestine, Duda explained.
“Some people notice that carbidopa-levodopa doesn’t work as well if taken with a high-protein meal.” He recommended taking carbidopa-levodopa 30 minutes before or 60 minutes after meals.
Rebecca Gilbert, MD, PhD, chief mission officer of the American Parkinson’s Disease Association, said that patients with Parkinson’s disease might want to avoid eating protein during the day, concentrating instead on carbohydrates and vegetables and saving the protein for the evening, which is closer to bedtime. Some evidence also supports the use of protein redistribution diets to enhance the clinical response to levodopa and reduce motor fluctuations.
What About Supplements?
It’s “hard to prove that one specific supplement can be protective against Parkinson’s disease because diet consists of many different components and the whole diet may be worth more than the sum of its parts,” Gilbert said. The evidence for individual supplements “isn’t robust enough to say they prevent or treat Parkinson’s disease.”
Research on the role of specific nutrients in Parkinson’s disease is conflicting, with no clear evidence supporting or refuting their benefits. For example, a study that followed participants for about 30 years showed no link between reduced Parkinson’s disease risk and vitamin B or folate intake.
On the other hand, there is research suggesting that certain vitamins may help reduce Parkinson’s disease risk, although these nutrients do not operate in isolation. For instance, one recent study showed a connection between vitamins C and E and reduced Parkinson’s disease risk, but factors such as body mass index and coffee consumption appeared to influence the strength of this association.
Consuming polyunsaturated fatty acids along with reducing saturated fatty acid intake has been tied to a reduced risk for Parkinson’s disease.
Additionally, certain foods may offer protective effects, including green and black tea, with consumption of three or more cups per day associated with a delay in motor symptom onset by 7.7 years. Foods high in nicotine content, such as those from the Solanaceae family — including peppers, tomatoes, tomato juice, and potatoes — have also been linked to potential protective benefits.
Diets rich in antioxidants, including carotenoids, lutein, and vitamins E and C, have been robustly linked to a reduced risk for parkinsonism and progression of parkinsonian symptoms in older adults.
Increasing the intake of dietary flavonoids, particularly tea, berry fruits, apples, red wine, and oranges or orange juice, can reduce Parkinson’s disease risk. One study showed that male participants in the highest quintile of total flavonoid consumption had a 40% lower Parkinson’s disease risk compared with those in the lowest quintile. Another study showed that flavonoid-rich foods were also associated with a lower risk for death in patients with Parkinson’s disease.
Food as Medicine
Although recent research shows that the drug development pipeline for Parkinson’s disease is robust, with a wide variety of approaches being developed and evaluated in phase 1 and 2, investigators note that only a limited number of disease-modifying treatments are transitioning to phase 3.
Duda noted that phytochemicals incorporated into the diet might target some of the same mechanisms that are targets of these drugs in development.
“Flavonoids have been shown to stabilize alpha-synuclein in vitro,” he said. “Caffeine, curcumin, resveratrol, and eliminating meat and dairy inhibit mTOR [mammalian target of rapamycin], and mTOR inhibition results in increased autophagy that may help clear alpha-synuclein. Genestein, an isoflavone in soybeans, protects dopaminergic neurons by inhibiting microglia activation. Flavonoids inhibit inflammation by inhibiting release of NO [nitric oxide] and pro-inflammatory cytokines,” he noted.
Ongoing studies of dietary interventions for Parkinson’s disease are exploring various areas, including the potential role of the ketogenic diet in protecting the gut microbiome, optimizing protein intake for muscle preservation and sleep, the effects of psyllium and wheat bran on weight and constipation, and the impact of a gluten-free diet.
Practical Tips for Healthy Eating
Gilbert emphasized that there are no medications or interventions currently available that can delay a Parkinson’s disease diagnosis by up to 17 years, as some dietary patterns have been shown to do, and she noted that it’s not possible to replicate the MeDi diet in a pill. However, she recommended a practical approach to eating that includes a diet low in ultraprocessed foods and high in beneficial nutrients. She encouraged people to shop for “real food” and enjoy a variety of colorful fruits and vegetables.
Duda acknowledged that motivating patients to follow a healthy diet can be difficult. As a result, the focus often shifts to making small adjustments and modifications. For example, he suggested that instead of pairing meat with French fries, people could opt for vegetables or add greens to their meals. Similarly, instead of having eggs and bacon for breakfast, they might choose oatmeal.
Preparing whole-food, plant-based meals may take more time than patients are accustomed to, so Duda suggests that, if possible, patients involve loved ones in both the meal preparation and the meal itself. He explained that a healthy meal can become an opportunity for bonding and that the key is educating them about new meal-related concepts.
Duda reported no relevant financial relationships with the pharmaceutical or food industries. He has received compensation from the Physicians Committee for Responsible Medicine for his lecture delivered at the conference and research grant support from the VA, the National Institutes of Health, the Michael J. Fox Foundation, and the Department of Defense unrelated to this topic. Gilbert reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
FDA OKs Novel Levodopa-Based Continuous Sub-Q Regimen for Parkinson’s Disease
Due to the progressive nature of Parkinson’s disease, “oral medications are eventually no longer as effective at motor symptom control and surgical treatment may be required. This new, non-surgical regimen provides continuous delivery of levodopa morning, day, and night,” Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorder Center at the University of South Florida, Tampa, said in a news release.
The FDA approval was supported by results of a 12-week, phase 3 study evaluating the efficacy of continuous subcutaneous infusion foscarbidopa/foslevodopa in adults with advanced Parkinson’s disease compared with oral immediate-release carbidopa/levodopa.
The study showed that patients treated with foscarbidopa/foslevodopa had superior improvement in motor fluctuations, with increased “on” time without troublesome dyskinesia and decreased “off” time, compared with peers receiving oral immediate-release carbidopa/levodopa.
At week 12, the increase in “on” time without troublesome dyskinesia was 2.72 hours for foscarbidopa/foslevodopa continuous infusion versus 0.97 hours for carbidopa/levodopa (P =.0083).
Improvements in “on” time were observed as early as the first week and persisted throughout the 12 weeks.
The approval of foscarbidopa/foslevodopa for advanced Parkinson’s disease was also supported by a 52-week, open-label study which evaluated the long-term safety and efficacy of the drug.
Most adverse reactions with foscarbidopa/foslevodopa were non-serious and mild or moderate in severity. The most frequent adverse reactions were infusion site events, hallucinations, and dyskinesia.
Full prescribing information is available online.
AbbVie said coverage for Medicare patients is expected in the second half of 2025.
A version of this article appeared on Medscape.com.
Due to the progressive nature of Parkinson’s disease, “oral medications are eventually no longer as effective at motor symptom control and surgical treatment may be required. This new, non-surgical regimen provides continuous delivery of levodopa morning, day, and night,” Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorder Center at the University of South Florida, Tampa, said in a news release.
The FDA approval was supported by results of a 12-week, phase 3 study evaluating the efficacy of continuous subcutaneous infusion foscarbidopa/foslevodopa in adults with advanced Parkinson’s disease compared with oral immediate-release carbidopa/levodopa.
The study showed that patients treated with foscarbidopa/foslevodopa had superior improvement in motor fluctuations, with increased “on” time without troublesome dyskinesia and decreased “off” time, compared with peers receiving oral immediate-release carbidopa/levodopa.
At week 12, the increase in “on” time without troublesome dyskinesia was 2.72 hours for foscarbidopa/foslevodopa continuous infusion versus 0.97 hours for carbidopa/levodopa (P =.0083).
Improvements in “on” time were observed as early as the first week and persisted throughout the 12 weeks.
The approval of foscarbidopa/foslevodopa for advanced Parkinson’s disease was also supported by a 52-week, open-label study which evaluated the long-term safety and efficacy of the drug.
Most adverse reactions with foscarbidopa/foslevodopa were non-serious and mild or moderate in severity. The most frequent adverse reactions were infusion site events, hallucinations, and dyskinesia.
Full prescribing information is available online.
AbbVie said coverage for Medicare patients is expected in the second half of 2025.
A version of this article appeared on Medscape.com.
Due to the progressive nature of Parkinson’s disease, “oral medications are eventually no longer as effective at motor symptom control and surgical treatment may be required. This new, non-surgical regimen provides continuous delivery of levodopa morning, day, and night,” Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorder Center at the University of South Florida, Tampa, said in a news release.
The FDA approval was supported by results of a 12-week, phase 3 study evaluating the efficacy of continuous subcutaneous infusion foscarbidopa/foslevodopa in adults with advanced Parkinson’s disease compared with oral immediate-release carbidopa/levodopa.
The study showed that patients treated with foscarbidopa/foslevodopa had superior improvement in motor fluctuations, with increased “on” time without troublesome dyskinesia and decreased “off” time, compared with peers receiving oral immediate-release carbidopa/levodopa.
At week 12, the increase in “on” time without troublesome dyskinesia was 2.72 hours for foscarbidopa/foslevodopa continuous infusion versus 0.97 hours for carbidopa/levodopa (P =.0083).
Improvements in “on” time were observed as early as the first week and persisted throughout the 12 weeks.
The approval of foscarbidopa/foslevodopa for advanced Parkinson’s disease was also supported by a 52-week, open-label study which evaluated the long-term safety and efficacy of the drug.
Most adverse reactions with foscarbidopa/foslevodopa were non-serious and mild or moderate in severity. The most frequent adverse reactions were infusion site events, hallucinations, and dyskinesia.
Full prescribing information is available online.
AbbVie said coverage for Medicare patients is expected in the second half of 2025.
A version of this article appeared on Medscape.com.
Is Pimavanserin a Better Option for Parkinson’s Psychosis?
PHILADELPHIA —
In the first prospective comparison of the two antipsychotics in this patient population, pimavanserin yielded significant improvement across all parameters of efficacy without worsening motor symptoms and was very well tolerated, said study investigator Amey Mane, MD, Sun Pharma Laboratories, Mumbai, India.
Psychosis occurs in about 50% patients with Parkinson’s disease and is a major risk factor for hospitalization, nursing home placement, and mortality.
Antipsychotics are used to treat Parkinson’s disease psychosis, but evidence for the efficacy of quetiapine is inconsistent and clozapine requires regular monitoring for agranulocytosis, said Dr. Mane. Cholinergic blockade by these drugs can also increase non-motor symptoms such as constipation, drooling, and cognitive impairment.
Pimavanserin is an oral 5-HT2A inverse agonist and antagonist and the only Food and Drug Administration–approved medication for Parkinson’s disease psychosis, he said. The drug was approved in 2016, and its label was updated in 2023 to clarify that it can be used to treat patients with Parkinson’s disease psychosis, who also have dementia.
“To the best of our understanding, this is the first completed prospective study of pimavanserin with an active comparator, quetiapine,” in Parkinson’s disease psychosis, he said.
The findings were presented in a late-breaking abstract session at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2024.
Primary Outcome at 56 Days
The assessor-blinded study enrolled 247 patients with Parkinson’s disease for at least 1 year, who were Hoehn and Yahr stage 3 or higher, with hallucinations and/or delusions on a stable dose of Parkinson’s disease medication for at least 4 weeks. The average duration of psychosis was 1.2 years.
Patients were randomly assigned to receive daily pimavanserin 34 mg or quetiapine 25-200 mg for 56 days and evaluated at baseline and days 14, 28, 42, and 56.
The mean change in Scale for the Assessment of Positive Symptoms–Parkinson’s disease (SAPS-PD) nine-item total scores improved from baseline in both groups at all visits (P < .0001) and was significantly greater at 42 days with pimavanserin than with quetiapine (−7.15 vs −6.33; P = .029).
The primary outcome of mean change in SAPS-PD total score at day 56 was −9.64 in the pimavanserin group and −8.37 in the quetiapine group (P = .008). The between-group difference was −1.27, and the upper bound of the 95% CI (−2.77 to 0.24) was lower than the prespecified margin of 0.9, demonstrating noninferiority, Dr. Mane said.
Secondary Endpoints and Safety
Pimavanserin was associated with significantly greater improvement than quetiapine for the following secondary outcomes:
- SAPS-Hallucinations and Delusions at day 42 (mean, −12.70 vs −11.40; P = .009) and day 56 (mean, −17.00 vs −15.60; P = .007)
- SAPS-Hallucinations at day 42 (mean, −5.61 vs −4.75; P = .01) and day 56 (mean, −7.33 vs −6.52; P = .02)
- Clinical Global Impression-Improvement score at day 56 (−1.90 vs −1.59; P = .01)
- Scales for Outcomes in Parkinson’s disease (SCOPA) scores for nighttime sleep at day 14 (−1.12 vs −0.85; P = .03) and SCOPA daytime wakefulness at day 28 (−2.42 vs −1.70; P = .01)
Treatment-emergent adverse events (TEAEs) were reported in 7.5% and 13.5% of the pimavanserin and quetiapine groups, respectively.
Five TEAEs, all of mild intensity, were reported as related to study drugs: Pyrexia (1), headache (1), and nasopharyngitis (2) with pimavanserin and headache (1) with quetiapine, Dr. Mane said. There was one unrelated fatal stroke in the quetiapine group. No drug discontinuations occurred because of TEAEs.
Delayed Onset of Action?
During a discussion of the results, Hubert Fernandez, MD, director, Center for Neurological Restoration, Cleveland Clinic in Ohio, asked whether the investigators observed a difference in onset between the two drugs.
“Our general impression in the United States is that pimavanserin has a slower uptake in efficacy as compared with quetiapine. If it [quetiapine] works, it works the next day or the day after, whereas with pimavanserin you have to wait for a week or 2. I was just wondering if that’s validated or just anecdotal experience,” he said.
Dr. Mane said the study showed no difference in efficacy at 14 days and greater improvement in efficacy between days 14 and 56.
Another attendee pointed out that quetiapine is particularly good at inducing sleep and asked whether some of the observed differences, especially early on, were due to the need to rapidly titrate quetiapine to induce sleep and get the sleep-wake cycle back on track.
“We did discuss this with most of our investigators, and they gave the same reason. It’s the titration with the quetiapine, and that’s why it’s seen in the early parts,” said Dr. Mane.
Reached for comment, Regina Katzenschlager, MD, Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Klinik Donaustadt, Vienna, Austria, said the majority of drugs commonly used for other types of psychosis cannot be used in PD because of motor worsening.
“Quetiapine is one of the very, very few options we have to treat people with Parkinson’s psychosis because it leads to little, if any, worsening and is the best tolerated,” she said. “Everything else is almost absolutely contraindicated. So that’s why an additional drug — this one has a slightly different mechanism — is incredibly helpful in the clinic because not everyone responds to quetiapine.”
Dr. Katzenschlager pointed out that pimavanserin is not approved in Europe and that the present study was conducted for regulatory purposes in India.
Dr. Mane is an employee of Sun Pharma Laboratories. Dr. Katzenschlager reported having no relevant financial relationships.
A version of this article appeared on Medscape.com.
PHILADELPHIA —
In the first prospective comparison of the two antipsychotics in this patient population, pimavanserin yielded significant improvement across all parameters of efficacy without worsening motor symptoms and was very well tolerated, said study investigator Amey Mane, MD, Sun Pharma Laboratories, Mumbai, India.
Psychosis occurs in about 50% patients with Parkinson’s disease and is a major risk factor for hospitalization, nursing home placement, and mortality.
Antipsychotics are used to treat Parkinson’s disease psychosis, but evidence for the efficacy of quetiapine is inconsistent and clozapine requires regular monitoring for agranulocytosis, said Dr. Mane. Cholinergic blockade by these drugs can also increase non-motor symptoms such as constipation, drooling, and cognitive impairment.
Pimavanserin is an oral 5-HT2A inverse agonist and antagonist and the only Food and Drug Administration–approved medication for Parkinson’s disease psychosis, he said. The drug was approved in 2016, and its label was updated in 2023 to clarify that it can be used to treat patients with Parkinson’s disease psychosis, who also have dementia.
“To the best of our understanding, this is the first completed prospective study of pimavanserin with an active comparator, quetiapine,” in Parkinson’s disease psychosis, he said.
The findings were presented in a late-breaking abstract session at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2024.
Primary Outcome at 56 Days
The assessor-blinded study enrolled 247 patients with Parkinson’s disease for at least 1 year, who were Hoehn and Yahr stage 3 or higher, with hallucinations and/or delusions on a stable dose of Parkinson’s disease medication for at least 4 weeks. The average duration of psychosis was 1.2 years.
Patients were randomly assigned to receive daily pimavanserin 34 mg or quetiapine 25-200 mg for 56 days and evaluated at baseline and days 14, 28, 42, and 56.
The mean change in Scale for the Assessment of Positive Symptoms–Parkinson’s disease (SAPS-PD) nine-item total scores improved from baseline in both groups at all visits (P < .0001) and was significantly greater at 42 days with pimavanserin than with quetiapine (−7.15 vs −6.33; P = .029).
The primary outcome of mean change in SAPS-PD total score at day 56 was −9.64 in the pimavanserin group and −8.37 in the quetiapine group (P = .008). The between-group difference was −1.27, and the upper bound of the 95% CI (−2.77 to 0.24) was lower than the prespecified margin of 0.9, demonstrating noninferiority, Dr. Mane said.
Secondary Endpoints and Safety
Pimavanserin was associated with significantly greater improvement than quetiapine for the following secondary outcomes:
- SAPS-Hallucinations and Delusions at day 42 (mean, −12.70 vs −11.40; P = .009) and day 56 (mean, −17.00 vs −15.60; P = .007)
- SAPS-Hallucinations at day 42 (mean, −5.61 vs −4.75; P = .01) and day 56 (mean, −7.33 vs −6.52; P = .02)
- Clinical Global Impression-Improvement score at day 56 (−1.90 vs −1.59; P = .01)
- Scales for Outcomes in Parkinson’s disease (SCOPA) scores for nighttime sleep at day 14 (−1.12 vs −0.85; P = .03) and SCOPA daytime wakefulness at day 28 (−2.42 vs −1.70; P = .01)
Treatment-emergent adverse events (TEAEs) were reported in 7.5% and 13.5% of the pimavanserin and quetiapine groups, respectively.
Five TEAEs, all of mild intensity, were reported as related to study drugs: Pyrexia (1), headache (1), and nasopharyngitis (2) with pimavanserin and headache (1) with quetiapine, Dr. Mane said. There was one unrelated fatal stroke in the quetiapine group. No drug discontinuations occurred because of TEAEs.
Delayed Onset of Action?
During a discussion of the results, Hubert Fernandez, MD, director, Center for Neurological Restoration, Cleveland Clinic in Ohio, asked whether the investigators observed a difference in onset between the two drugs.
“Our general impression in the United States is that pimavanserin has a slower uptake in efficacy as compared with quetiapine. If it [quetiapine] works, it works the next day or the day after, whereas with pimavanserin you have to wait for a week or 2. I was just wondering if that’s validated or just anecdotal experience,” he said.
Dr. Mane said the study showed no difference in efficacy at 14 days and greater improvement in efficacy between days 14 and 56.
Another attendee pointed out that quetiapine is particularly good at inducing sleep and asked whether some of the observed differences, especially early on, were due to the need to rapidly titrate quetiapine to induce sleep and get the sleep-wake cycle back on track.
“We did discuss this with most of our investigators, and they gave the same reason. It’s the titration with the quetiapine, and that’s why it’s seen in the early parts,” said Dr. Mane.
Reached for comment, Regina Katzenschlager, MD, Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Klinik Donaustadt, Vienna, Austria, said the majority of drugs commonly used for other types of psychosis cannot be used in PD because of motor worsening.
“Quetiapine is one of the very, very few options we have to treat people with Parkinson’s psychosis because it leads to little, if any, worsening and is the best tolerated,” she said. “Everything else is almost absolutely contraindicated. So that’s why an additional drug — this one has a slightly different mechanism — is incredibly helpful in the clinic because not everyone responds to quetiapine.”
Dr. Katzenschlager pointed out that pimavanserin is not approved in Europe and that the present study was conducted for regulatory purposes in India.
Dr. Mane is an employee of Sun Pharma Laboratories. Dr. Katzenschlager reported having no relevant financial relationships.
A version of this article appeared on Medscape.com.
PHILADELPHIA —
In the first prospective comparison of the two antipsychotics in this patient population, pimavanserin yielded significant improvement across all parameters of efficacy without worsening motor symptoms and was very well tolerated, said study investigator Amey Mane, MD, Sun Pharma Laboratories, Mumbai, India.
Psychosis occurs in about 50% patients with Parkinson’s disease and is a major risk factor for hospitalization, nursing home placement, and mortality.
Antipsychotics are used to treat Parkinson’s disease psychosis, but evidence for the efficacy of quetiapine is inconsistent and clozapine requires regular monitoring for agranulocytosis, said Dr. Mane. Cholinergic blockade by these drugs can also increase non-motor symptoms such as constipation, drooling, and cognitive impairment.
Pimavanserin is an oral 5-HT2A inverse agonist and antagonist and the only Food and Drug Administration–approved medication for Parkinson’s disease psychosis, he said. The drug was approved in 2016, and its label was updated in 2023 to clarify that it can be used to treat patients with Parkinson’s disease psychosis, who also have dementia.
“To the best of our understanding, this is the first completed prospective study of pimavanserin with an active comparator, quetiapine,” in Parkinson’s disease psychosis, he said.
The findings were presented in a late-breaking abstract session at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2024.
Primary Outcome at 56 Days
The assessor-blinded study enrolled 247 patients with Parkinson’s disease for at least 1 year, who were Hoehn and Yahr stage 3 or higher, with hallucinations and/or delusions on a stable dose of Parkinson’s disease medication for at least 4 weeks. The average duration of psychosis was 1.2 years.
Patients were randomly assigned to receive daily pimavanserin 34 mg or quetiapine 25-200 mg for 56 days and evaluated at baseline and days 14, 28, 42, and 56.
The mean change in Scale for the Assessment of Positive Symptoms–Parkinson’s disease (SAPS-PD) nine-item total scores improved from baseline in both groups at all visits (P < .0001) and was significantly greater at 42 days with pimavanserin than with quetiapine (−7.15 vs −6.33; P = .029).
The primary outcome of mean change in SAPS-PD total score at day 56 was −9.64 in the pimavanserin group and −8.37 in the quetiapine group (P = .008). The between-group difference was −1.27, and the upper bound of the 95% CI (−2.77 to 0.24) was lower than the prespecified margin of 0.9, demonstrating noninferiority, Dr. Mane said.
Secondary Endpoints and Safety
Pimavanserin was associated with significantly greater improvement than quetiapine for the following secondary outcomes:
- SAPS-Hallucinations and Delusions at day 42 (mean, −12.70 vs −11.40; P = .009) and day 56 (mean, −17.00 vs −15.60; P = .007)
- SAPS-Hallucinations at day 42 (mean, −5.61 vs −4.75; P = .01) and day 56 (mean, −7.33 vs −6.52; P = .02)
- Clinical Global Impression-Improvement score at day 56 (−1.90 vs −1.59; P = .01)
- Scales for Outcomes in Parkinson’s disease (SCOPA) scores for nighttime sleep at day 14 (−1.12 vs −0.85; P = .03) and SCOPA daytime wakefulness at day 28 (−2.42 vs −1.70; P = .01)
Treatment-emergent adverse events (TEAEs) were reported in 7.5% and 13.5% of the pimavanserin and quetiapine groups, respectively.
Five TEAEs, all of mild intensity, were reported as related to study drugs: Pyrexia (1), headache (1), and nasopharyngitis (2) with pimavanserin and headache (1) with quetiapine, Dr. Mane said. There was one unrelated fatal stroke in the quetiapine group. No drug discontinuations occurred because of TEAEs.
Delayed Onset of Action?
During a discussion of the results, Hubert Fernandez, MD, director, Center for Neurological Restoration, Cleveland Clinic in Ohio, asked whether the investigators observed a difference in onset between the two drugs.
“Our general impression in the United States is that pimavanserin has a slower uptake in efficacy as compared with quetiapine. If it [quetiapine] works, it works the next day or the day after, whereas with pimavanserin you have to wait for a week or 2. I was just wondering if that’s validated or just anecdotal experience,” he said.
Dr. Mane said the study showed no difference in efficacy at 14 days and greater improvement in efficacy between days 14 and 56.
Another attendee pointed out that quetiapine is particularly good at inducing sleep and asked whether some of the observed differences, especially early on, were due to the need to rapidly titrate quetiapine to induce sleep and get the sleep-wake cycle back on track.
“We did discuss this with most of our investigators, and they gave the same reason. It’s the titration with the quetiapine, and that’s why it’s seen in the early parts,” said Dr. Mane.
Reached for comment, Regina Katzenschlager, MD, Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Klinik Donaustadt, Vienna, Austria, said the majority of drugs commonly used for other types of psychosis cannot be used in PD because of motor worsening.
“Quetiapine is one of the very, very few options we have to treat people with Parkinson’s psychosis because it leads to little, if any, worsening and is the best tolerated,” she said. “Everything else is almost absolutely contraindicated. So that’s why an additional drug — this one has a slightly different mechanism — is incredibly helpful in the clinic because not everyone responds to quetiapine.”
Dr. Katzenschlager pointed out that pimavanserin is not approved in Europe and that the present study was conducted for regulatory purposes in India.
Dr. Mane is an employee of Sun Pharma Laboratories. Dr. Katzenschlager reported having no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM MDS 2024
SGLT2 Inhibitor Reduces Risk for Neurodegenerative Diseases in T2D
MADRID — Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) show significant reductions in the risk of developing neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and Parkinson’s disease, compared with those treated with other antidiabetic drugs, results from a large population-based cohort show.
“This was the largest nationwide population-based longitudinal cohort study to investigate the association between the use of SGLT2 inhibitors and the incidence of all-cause dementia and Parkinson’s disease,” said first author Hae Kyung Kim, MD, of the Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, in presenting the findings at the annual meeting of the European Association for the Study of Diabetes.
Type 2 diabetes is known to increase the risk for neurodegenerative diseases such as dementia or Alzheimer’s disease, said Dr. Kim. Key factors attributed to the risk include shared pathophysiological mechanisms such as central nervous system insulin resistance and reduced cerebral glucose metabolism.
While research is lacking on the role of antidiabetic drugs in the treatment of neurodegenerative diseases, the researcher noted that “SGLT2 inhibitors, which have shown significant cardiorenal benefits and enhanced energy metabolism through ketogenesis, offer promise.”
To further investigate, Dr. Kim and her colleagues conducted the retrospective study, evaluating data on more than 1.3 million enrollees in Korea’s National Health Insurance Service Database who were aged 40 years or older, diagnosed with type 2 diabetes, and had initiated antidiabetic drugs between September 2014 and December 2019.
In the propensity score analysis, 358,862 patients were matched 1:1, in groups of 179,431 participants each, based on whether they were treated with SGLT2is or other oral antidiabetic drugs. Patients with a history of neurodegenerative disease, cancer, or use of glucagon-like peptide 1 receptor agonists were excluded.
The patients had a mean age of 57.8 years, 57.9% were men, and 6837 had incident dementia or Parkinson’s disease events reported.
With a mean follow-up of 2.88 years, after adjustment for key variables, those treated with SGLT2is had a 19% reduced risk of developing Alzheimer’s disease (adjusted hazard ratio [aHR], 0.81), a 31% reduced risk for vascular dementia (aHR, 0.69), and a 20% reduced risk for Parkinson’s disease (aHR, 0.80) compared with the non-SGLT2i group.
Furthermore, those receiving SGLT2i treatment had a 21% reduced risk for all-cause dementia (aHR, 0.79) and a 22% reduced risk for all-cause dementia and Parkinson’s disease compared with the oral antidiabetic drug group (aHR, 0.78) with a 6-month drug use lag period.
The association was observed regardless of SGLT2i exposure duration. Subgroup analyses indicated that the reductions in neurodegenerative disorders among those receiving SGLT2is were not associated with factors including age, sex, body mass index, blood pressure, glucose, lipid profiles, kidney function, health behaviors, comorbidities, diabetic complications, or other medication use.
Dr. Kim speculated that mechanisms underlying the reduced dementia risk could include SGLT2i effects of mitigating the common severe risk factors of type 2 diabetes and neurodegenerative diseases, including hypertension, heart failure, and chronic kidney disease, and improving hyperperfusion in the heart and cerebral vascular insufficiency.
Commenting on the study to this news organization, Erik H. Serné, MD, of the VU University Medical Centre, Amsterdam, the Netherlands, who comoderated the session, noted that “people with type 2 diabetes have a 50%-100% increased risk of developing dementia, particularly Alzheimer’s disease and vascular dementia.”
“The increasing prevalence of both conditions poses significant public health challenges, highlighting the need for effective prevention strategies and interventions.”
Currently, treatments for dementia are limited, with most primarily addressing symptoms and not the underlying cause of the neurodegenerative disease, he said.
He noted that, in addition to the effects mentioned by Dr. Kim, SGLT2is are also speculated to provide potential neuroprotective effects through improved glycemic control and insulin sensitivity, reduced inflammation and oxidative stress, enhanced mitochondrial function and energy metabolism, and reduced beta-amyloid and tau pathology.
“These mechanisms collectively may reduce the risk of cognitive decline, particularly in diabetic patients, and warrant further investigation in clinical trials to solidify the neuroprotective role of SGLT2 inhibitors,” said Dr. Serné.
In addition to their benefits in type 2 diabetes, SGLT2is “now offer hope in the prevention of dementia, a disease that has very limited therapeutic options thus far. The current data [presented by Dr. Kim] seem to corroborate this,” he added.
Dr. Kim and Dr. Serné had no disclosures to report.
A version of this article first appeared on Medscape.com.
MADRID — Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) show significant reductions in the risk of developing neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and Parkinson’s disease, compared with those treated with other antidiabetic drugs, results from a large population-based cohort show.
“This was the largest nationwide population-based longitudinal cohort study to investigate the association between the use of SGLT2 inhibitors and the incidence of all-cause dementia and Parkinson’s disease,” said first author Hae Kyung Kim, MD, of the Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, in presenting the findings at the annual meeting of the European Association for the Study of Diabetes.
Type 2 diabetes is known to increase the risk for neurodegenerative diseases such as dementia or Alzheimer’s disease, said Dr. Kim. Key factors attributed to the risk include shared pathophysiological mechanisms such as central nervous system insulin resistance and reduced cerebral glucose metabolism.
While research is lacking on the role of antidiabetic drugs in the treatment of neurodegenerative diseases, the researcher noted that “SGLT2 inhibitors, which have shown significant cardiorenal benefits and enhanced energy metabolism through ketogenesis, offer promise.”
To further investigate, Dr. Kim and her colleagues conducted the retrospective study, evaluating data on more than 1.3 million enrollees in Korea’s National Health Insurance Service Database who were aged 40 years or older, diagnosed with type 2 diabetes, and had initiated antidiabetic drugs between September 2014 and December 2019.
In the propensity score analysis, 358,862 patients were matched 1:1, in groups of 179,431 participants each, based on whether they were treated with SGLT2is or other oral antidiabetic drugs. Patients with a history of neurodegenerative disease, cancer, or use of glucagon-like peptide 1 receptor agonists were excluded.
The patients had a mean age of 57.8 years, 57.9% were men, and 6837 had incident dementia or Parkinson’s disease events reported.
With a mean follow-up of 2.88 years, after adjustment for key variables, those treated with SGLT2is had a 19% reduced risk of developing Alzheimer’s disease (adjusted hazard ratio [aHR], 0.81), a 31% reduced risk for vascular dementia (aHR, 0.69), and a 20% reduced risk for Parkinson’s disease (aHR, 0.80) compared with the non-SGLT2i group.
Furthermore, those receiving SGLT2i treatment had a 21% reduced risk for all-cause dementia (aHR, 0.79) and a 22% reduced risk for all-cause dementia and Parkinson’s disease compared with the oral antidiabetic drug group (aHR, 0.78) with a 6-month drug use lag period.
The association was observed regardless of SGLT2i exposure duration. Subgroup analyses indicated that the reductions in neurodegenerative disorders among those receiving SGLT2is were not associated with factors including age, sex, body mass index, blood pressure, glucose, lipid profiles, kidney function, health behaviors, comorbidities, diabetic complications, or other medication use.
Dr. Kim speculated that mechanisms underlying the reduced dementia risk could include SGLT2i effects of mitigating the common severe risk factors of type 2 diabetes and neurodegenerative diseases, including hypertension, heart failure, and chronic kidney disease, and improving hyperperfusion in the heart and cerebral vascular insufficiency.
Commenting on the study to this news organization, Erik H. Serné, MD, of the VU University Medical Centre, Amsterdam, the Netherlands, who comoderated the session, noted that “people with type 2 diabetes have a 50%-100% increased risk of developing dementia, particularly Alzheimer’s disease and vascular dementia.”
“The increasing prevalence of both conditions poses significant public health challenges, highlighting the need for effective prevention strategies and interventions.”
Currently, treatments for dementia are limited, with most primarily addressing symptoms and not the underlying cause of the neurodegenerative disease, he said.
He noted that, in addition to the effects mentioned by Dr. Kim, SGLT2is are also speculated to provide potential neuroprotective effects through improved glycemic control and insulin sensitivity, reduced inflammation and oxidative stress, enhanced mitochondrial function and energy metabolism, and reduced beta-amyloid and tau pathology.
“These mechanisms collectively may reduce the risk of cognitive decline, particularly in diabetic patients, and warrant further investigation in clinical trials to solidify the neuroprotective role of SGLT2 inhibitors,” said Dr. Serné.
In addition to their benefits in type 2 diabetes, SGLT2is “now offer hope in the prevention of dementia, a disease that has very limited therapeutic options thus far. The current data [presented by Dr. Kim] seem to corroborate this,” he added.
Dr. Kim and Dr. Serné had no disclosures to report.
A version of this article first appeared on Medscape.com.
MADRID — Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) show significant reductions in the risk of developing neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and Parkinson’s disease, compared with those treated with other antidiabetic drugs, results from a large population-based cohort show.
“This was the largest nationwide population-based longitudinal cohort study to investigate the association between the use of SGLT2 inhibitors and the incidence of all-cause dementia and Parkinson’s disease,” said first author Hae Kyung Kim, MD, of the Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, in presenting the findings at the annual meeting of the European Association for the Study of Diabetes.
Type 2 diabetes is known to increase the risk for neurodegenerative diseases such as dementia or Alzheimer’s disease, said Dr. Kim. Key factors attributed to the risk include shared pathophysiological mechanisms such as central nervous system insulin resistance and reduced cerebral glucose metabolism.
While research is lacking on the role of antidiabetic drugs in the treatment of neurodegenerative diseases, the researcher noted that “SGLT2 inhibitors, which have shown significant cardiorenal benefits and enhanced energy metabolism through ketogenesis, offer promise.”
To further investigate, Dr. Kim and her colleagues conducted the retrospective study, evaluating data on more than 1.3 million enrollees in Korea’s National Health Insurance Service Database who were aged 40 years or older, diagnosed with type 2 diabetes, and had initiated antidiabetic drugs between September 2014 and December 2019.
In the propensity score analysis, 358,862 patients were matched 1:1, in groups of 179,431 participants each, based on whether they were treated with SGLT2is or other oral antidiabetic drugs. Patients with a history of neurodegenerative disease, cancer, or use of glucagon-like peptide 1 receptor agonists were excluded.
The patients had a mean age of 57.8 years, 57.9% were men, and 6837 had incident dementia or Parkinson’s disease events reported.
With a mean follow-up of 2.88 years, after adjustment for key variables, those treated with SGLT2is had a 19% reduced risk of developing Alzheimer’s disease (adjusted hazard ratio [aHR], 0.81), a 31% reduced risk for vascular dementia (aHR, 0.69), and a 20% reduced risk for Parkinson’s disease (aHR, 0.80) compared with the non-SGLT2i group.
Furthermore, those receiving SGLT2i treatment had a 21% reduced risk for all-cause dementia (aHR, 0.79) and a 22% reduced risk for all-cause dementia and Parkinson’s disease compared with the oral antidiabetic drug group (aHR, 0.78) with a 6-month drug use lag period.
The association was observed regardless of SGLT2i exposure duration. Subgroup analyses indicated that the reductions in neurodegenerative disorders among those receiving SGLT2is were not associated with factors including age, sex, body mass index, blood pressure, glucose, lipid profiles, kidney function, health behaviors, comorbidities, diabetic complications, or other medication use.
Dr. Kim speculated that mechanisms underlying the reduced dementia risk could include SGLT2i effects of mitigating the common severe risk factors of type 2 diabetes and neurodegenerative diseases, including hypertension, heart failure, and chronic kidney disease, and improving hyperperfusion in the heart and cerebral vascular insufficiency.
Commenting on the study to this news organization, Erik H. Serné, MD, of the VU University Medical Centre, Amsterdam, the Netherlands, who comoderated the session, noted that “people with type 2 diabetes have a 50%-100% increased risk of developing dementia, particularly Alzheimer’s disease and vascular dementia.”
“The increasing prevalence of both conditions poses significant public health challenges, highlighting the need for effective prevention strategies and interventions.”
Currently, treatments for dementia are limited, with most primarily addressing symptoms and not the underlying cause of the neurodegenerative disease, he said.
He noted that, in addition to the effects mentioned by Dr. Kim, SGLT2is are also speculated to provide potential neuroprotective effects through improved glycemic control and insulin sensitivity, reduced inflammation and oxidative stress, enhanced mitochondrial function and energy metabolism, and reduced beta-amyloid and tau pathology.
“These mechanisms collectively may reduce the risk of cognitive decline, particularly in diabetic patients, and warrant further investigation in clinical trials to solidify the neuroprotective role of SGLT2 inhibitors,” said Dr. Serné.
In addition to their benefits in type 2 diabetes, SGLT2is “now offer hope in the prevention of dementia, a disease that has very limited therapeutic options thus far. The current data [presented by Dr. Kim] seem to corroborate this,” he added.
Dr. Kim and Dr. Serné had no disclosures to report.
A version of this article first appeared on Medscape.com.
FROM EASD 2024
Parkinson’s Risk in Women and History of Migraine: New Data
TOPLINE:
A history of migraine is not associated with an elevated risk for Parkinson’s disease (PD) in women, regardless of headache frequency or migraine subtype, a new study suggests.
METHODOLOGY:
- Researchers analyzed data on 39,312 women health professionals aged ≥ 45 years and having no history of PD who enrolled in the Women’s Health Study between 1992 and 1995 and were followed until 2021.
- At baseline, 7321 women (18.6%) had migraine.
- The mean follow-up duration was 22 years.
- The primary outcome was a self-reported, physician-confirmed diagnosis of PD.
TAKEAWAY:
- During the study period, 685 women self-reported a diagnosis of PD.
- Of these, 18.7% of reported cases were in women with any migraine and 81.3% in women without migraine.
- No significant association was found between PD risk and a history of migraine, migraine subtypes (with or without aura), or migraine frequency.
- Migraine was not associated with a higher risk for PD than that of nonmigraine headaches.
IN PRACTICE:
“These results are reassuring for women who have migraine, which itself causes many burdens, that they don’t have to worry about an increased risk of Parkinson’s disease in the future,” study author Tobias Kurth, Charité - Universitätsmedizin Berlin, Germany, said in a press release.
SOURCE:
The study was led by Ricarda S. Schulz, MSc, Charité - Universitätsmedizin Berlin. It was published online in Neurology.
LIMITATIONS:
The study’s findings may not be generalizable to other populations, such as men and non-White individuals. The self-reported data on migraine and PD may be subject to inaccuracies. PD is often not diagnosed until symptoms have reached an advanced stage, potentially leading to cases being underreported. Changes in the status and frequency of migraine over the study period were not accounted for, which may have affected the results.
DISCLOSURES:
The authors did not disclose any specific funding for this work. The Women’s Health Study was supported by the National Cancer Institute and National Heart, Lung, and Blood Institute. Two authors reported having financial ties outside this work. Full disclosures are available in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
A history of migraine is not associated with an elevated risk for Parkinson’s disease (PD) in women, regardless of headache frequency or migraine subtype, a new study suggests.
METHODOLOGY:
- Researchers analyzed data on 39,312 women health professionals aged ≥ 45 years and having no history of PD who enrolled in the Women’s Health Study between 1992 and 1995 and were followed until 2021.
- At baseline, 7321 women (18.6%) had migraine.
- The mean follow-up duration was 22 years.
- The primary outcome was a self-reported, physician-confirmed diagnosis of PD.
TAKEAWAY:
- During the study period, 685 women self-reported a diagnosis of PD.
- Of these, 18.7% of reported cases were in women with any migraine and 81.3% in women without migraine.
- No significant association was found between PD risk and a history of migraine, migraine subtypes (with or without aura), or migraine frequency.
- Migraine was not associated with a higher risk for PD than that of nonmigraine headaches.
IN PRACTICE:
“These results are reassuring for women who have migraine, which itself causes many burdens, that they don’t have to worry about an increased risk of Parkinson’s disease in the future,” study author Tobias Kurth, Charité - Universitätsmedizin Berlin, Germany, said in a press release.
SOURCE:
The study was led by Ricarda S. Schulz, MSc, Charité - Universitätsmedizin Berlin. It was published online in Neurology.
LIMITATIONS:
The study’s findings may not be generalizable to other populations, such as men and non-White individuals. The self-reported data on migraine and PD may be subject to inaccuracies. PD is often not diagnosed until symptoms have reached an advanced stage, potentially leading to cases being underreported. Changes in the status and frequency of migraine over the study period were not accounted for, which may have affected the results.
DISCLOSURES:
The authors did not disclose any specific funding for this work. The Women’s Health Study was supported by the National Cancer Institute and National Heart, Lung, and Blood Institute. Two authors reported having financial ties outside this work. Full disclosures are available in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
A history of migraine is not associated with an elevated risk for Parkinson’s disease (PD) in women, regardless of headache frequency or migraine subtype, a new study suggests.
METHODOLOGY:
- Researchers analyzed data on 39,312 women health professionals aged ≥ 45 years and having no history of PD who enrolled in the Women’s Health Study between 1992 and 1995 and were followed until 2021.
- At baseline, 7321 women (18.6%) had migraine.
- The mean follow-up duration was 22 years.
- The primary outcome was a self-reported, physician-confirmed diagnosis of PD.
TAKEAWAY:
- During the study period, 685 women self-reported a diagnosis of PD.
- Of these, 18.7% of reported cases were in women with any migraine and 81.3% in women without migraine.
- No significant association was found between PD risk and a history of migraine, migraine subtypes (with or without aura), or migraine frequency.
- Migraine was not associated with a higher risk for PD than that of nonmigraine headaches.
IN PRACTICE:
“These results are reassuring for women who have migraine, which itself causes many burdens, that they don’t have to worry about an increased risk of Parkinson’s disease in the future,” study author Tobias Kurth, Charité - Universitätsmedizin Berlin, Germany, said in a press release.
SOURCE:
The study was led by Ricarda S. Schulz, MSc, Charité - Universitätsmedizin Berlin. It was published online in Neurology.
LIMITATIONS:
The study’s findings may not be generalizable to other populations, such as men and non-White individuals. The self-reported data on migraine and PD may be subject to inaccuracies. PD is often not diagnosed until symptoms have reached an advanced stage, potentially leading to cases being underreported. Changes in the status and frequency of migraine over the study period were not accounted for, which may have affected the results.
DISCLOSURES:
The authors did not disclose any specific funding for this work. The Women’s Health Study was supported by the National Cancer Institute and National Heart, Lung, and Blood Institute. Two authors reported having financial ties outside this work. Full disclosures are available in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Fecal Transplant: A New Approach for Parkinson’s Disease?
, results of a new, randomized placebo-controlled trial show.
However, investigators discovered some interesting insights from the study, which they believe may help in designing future “improved, and hopefully successful, trials” with the intervention.
“Further studies — for example, through modified fecal microbiota transplantation approaches or bowel cleansing — are warranted,” they concluded.
The study was published online in JAMA Neurology.
Gut Dysfunction: An Early Symptom
Investigators led by Filip Scheperjans, MD, Helsinki University Hospital, Finland, explained that gut dysfunction is a prevalent, early symptom in Parkinson’s disease and is associated with more rapid disease progression.
Interventions targeting gut microbiota, such as FMT, have shown promising symptomatic, and potentially neuroprotective, effects in animal models of Parkinson’s disease.
Although several randomized clinical trials suggest efficacy of probiotics for Parkinson’s disease-related constipation, only limited clinical information on FMT is available.
In the current trial, 48 patients with Parkinson’s disease aged 35-75 years with mild to moderate symptoms and dysbiosis of fecal microbiota were randomized in a 2:1 ratio to receive FMT or placebo infused into the cecum via colonoscopy.
All patients had whole-bowel lavage starting the day before the colonoscopy. Fecal microbiota transplantation was administered as a single-dose and without antibiotic pretreatment.
Active treatment was a freeze-stored preparation of 30 g of feces from one of two donors who were healthy individuals without dysbiosis. The preparation was mixed with 150 mL of sterile physiologic saline and 20 mL of 85% glycerol for cryoprotection to improve viability of microbes. Placebo was the carrier solution alone, consisting of 180 mL of sterile physiologic saline and 20 mL of 85% glycerol.
The primary endpoint, a change in Parkinson’s disease symptoms as assessed on the Unified Parkinson’s Disease Rating Scale (UPDRS) at 6 months, did not differ between the two study groups.
Gastrointestinal adverse events were more frequent in the FMT group, occurring in 16 patients (53%) versus one patient (7%) in the placebo group. But no major safety concerns were observed.
Secondary outcomes and post hoc analyses showed a greater increase in dopaminergic medication, which may indicate faster disease progression, but also improvement in certain motor and nonmotor outcomes in the placebo group.
Microbiota changes were more pronounced after FMT, but dysbiosis status was reversed more frequently in the placebo group.
The researchers noted that the apparent futility in this trial is in contrast to several previous small clinical studies of fecal transplant that have suggested the potential for improvement of Parkinson’s disease symptoms.
In addition, encouraging results from the probiotics field suggest that an impact on motor and nonmotor Parkinson’s disease symptoms through gut microbiota manipulation is possible.
The researchers raised the possibility that the placebo procedure was not an inert comparator, given the relatively strong and sustained gut microbiota alteration and dysbiosis conversion observed in the placebo group, and suggested that the colonic cleansing procedure may also have had some beneficial effect.
“It seems possible that, after cleansing of a dysbiotic gut microbiota, recolonization leads to a more physiologic gut microbiota composition with symptom improvement in the placebo group. This warrants further exploration of modified fecal microbiota transplantation approaches and bowel cleansing in Parkinson’s disease,” they concluded.
Distinct Gut Microbiome
In an accompanying editorial, Timothy R. Sampson, PhD, assistant professor, Department of Cell Biology, Emory University School of Medicine, Atlanta, pointed out that dozens of independent studies have now demonstrated a distinct gut microbiome composition associated with Parkinson’s disease, and experimental data suggest that this has the capacity to incite inflammatory responses; degrade intestinal mucosa; and dysregulate a number of neuroactive and amyloidogenic molecules, which could contribute to the disease.
He noted that three other small placebo-controlled studies of fecal transplantation in Parkinson’s disease showed slightly more robust responses in the active treatment group, including improvements in UPDRS scores and gastrointestinal symptoms.
However, these studies tested different FMT procedures, including lyophilized oral capsules given at different dosing frequencies and either nasojejunal or colonic transfusion following a standard bowel preparation.
In addition, there is no consensus on pretransplant procedures, such as antibiotics or bowel clearance, and the choice of donor microbiome is probably essential, because there may be certain microbes required to shift the entire community, Dr. Sampson wrote.
Understanding how microbial contributions directly relate to Parkinson’s disease would identify individuals more likely to respond to peripheral interventions, and further exploration is needed to shed light on particular microbes that warrant targeting for either enrichment or depletion, he added.
“Despite a lack of primary end point efficacy in this latest study, in-depth comparison across these studies may reveal opportunities to refine fecal microbiota transplantation approaches. Together, these studies will continue to refine the hypothesis of a microbial contribution to Parkinson’s disease and reveal new therapeutic avenues,” Dr. Sampson concluded.
‘Planting Grass in a Yard Full of Weeds’
Commenting on the research, James Beck, PhD, chief scientific officer of the Parkinson’s Foundation, New York, said that whether FMT are helpful remains to be determined.
“The key question that needs to be solved is how to best perform these transplants. One issue is that you cannot plant grass when the yard is full of weeds. However, if you take too hard an approach killing the weeds — that is, with powerful antibiotics — you jeopardize the new grass, or in this case, the bacteria in the transplant. Solving that issue will be important as we consider whether this is effective or not.”
Dr. Beck added that there is still much to be learned from research into the gut microbiota. “I am hopeful with additional effort we will have answers soon.”
A version of this article appeared on Medscape.com.
, results of a new, randomized placebo-controlled trial show.
However, investigators discovered some interesting insights from the study, which they believe may help in designing future “improved, and hopefully successful, trials” with the intervention.
“Further studies — for example, through modified fecal microbiota transplantation approaches or bowel cleansing — are warranted,” they concluded.
The study was published online in JAMA Neurology.
Gut Dysfunction: An Early Symptom
Investigators led by Filip Scheperjans, MD, Helsinki University Hospital, Finland, explained that gut dysfunction is a prevalent, early symptom in Parkinson’s disease and is associated with more rapid disease progression.
Interventions targeting gut microbiota, such as FMT, have shown promising symptomatic, and potentially neuroprotective, effects in animal models of Parkinson’s disease.
Although several randomized clinical trials suggest efficacy of probiotics for Parkinson’s disease-related constipation, only limited clinical information on FMT is available.
In the current trial, 48 patients with Parkinson’s disease aged 35-75 years with mild to moderate symptoms and dysbiosis of fecal microbiota were randomized in a 2:1 ratio to receive FMT or placebo infused into the cecum via colonoscopy.
All patients had whole-bowel lavage starting the day before the colonoscopy. Fecal microbiota transplantation was administered as a single-dose and without antibiotic pretreatment.
Active treatment was a freeze-stored preparation of 30 g of feces from one of two donors who were healthy individuals without dysbiosis. The preparation was mixed with 150 mL of sterile physiologic saline and 20 mL of 85% glycerol for cryoprotection to improve viability of microbes. Placebo was the carrier solution alone, consisting of 180 mL of sterile physiologic saline and 20 mL of 85% glycerol.
The primary endpoint, a change in Parkinson’s disease symptoms as assessed on the Unified Parkinson’s Disease Rating Scale (UPDRS) at 6 months, did not differ between the two study groups.
Gastrointestinal adverse events were more frequent in the FMT group, occurring in 16 patients (53%) versus one patient (7%) in the placebo group. But no major safety concerns were observed.
Secondary outcomes and post hoc analyses showed a greater increase in dopaminergic medication, which may indicate faster disease progression, but also improvement in certain motor and nonmotor outcomes in the placebo group.
Microbiota changes were more pronounced after FMT, but dysbiosis status was reversed more frequently in the placebo group.
The researchers noted that the apparent futility in this trial is in contrast to several previous small clinical studies of fecal transplant that have suggested the potential for improvement of Parkinson’s disease symptoms.
In addition, encouraging results from the probiotics field suggest that an impact on motor and nonmotor Parkinson’s disease symptoms through gut microbiota manipulation is possible.
The researchers raised the possibility that the placebo procedure was not an inert comparator, given the relatively strong and sustained gut microbiota alteration and dysbiosis conversion observed in the placebo group, and suggested that the colonic cleansing procedure may also have had some beneficial effect.
“It seems possible that, after cleansing of a dysbiotic gut microbiota, recolonization leads to a more physiologic gut microbiota composition with symptom improvement in the placebo group. This warrants further exploration of modified fecal microbiota transplantation approaches and bowel cleansing in Parkinson’s disease,” they concluded.
Distinct Gut Microbiome
In an accompanying editorial, Timothy R. Sampson, PhD, assistant professor, Department of Cell Biology, Emory University School of Medicine, Atlanta, pointed out that dozens of independent studies have now demonstrated a distinct gut microbiome composition associated with Parkinson’s disease, and experimental data suggest that this has the capacity to incite inflammatory responses; degrade intestinal mucosa; and dysregulate a number of neuroactive and amyloidogenic molecules, which could contribute to the disease.
He noted that three other small placebo-controlled studies of fecal transplantation in Parkinson’s disease showed slightly more robust responses in the active treatment group, including improvements in UPDRS scores and gastrointestinal symptoms.
However, these studies tested different FMT procedures, including lyophilized oral capsules given at different dosing frequencies and either nasojejunal or colonic transfusion following a standard bowel preparation.
In addition, there is no consensus on pretransplant procedures, such as antibiotics or bowel clearance, and the choice of donor microbiome is probably essential, because there may be certain microbes required to shift the entire community, Dr. Sampson wrote.
Understanding how microbial contributions directly relate to Parkinson’s disease would identify individuals more likely to respond to peripheral interventions, and further exploration is needed to shed light on particular microbes that warrant targeting for either enrichment or depletion, he added.
“Despite a lack of primary end point efficacy in this latest study, in-depth comparison across these studies may reveal opportunities to refine fecal microbiota transplantation approaches. Together, these studies will continue to refine the hypothesis of a microbial contribution to Parkinson’s disease and reveal new therapeutic avenues,” Dr. Sampson concluded.
‘Planting Grass in a Yard Full of Weeds’
Commenting on the research, James Beck, PhD, chief scientific officer of the Parkinson’s Foundation, New York, said that whether FMT are helpful remains to be determined.
“The key question that needs to be solved is how to best perform these transplants. One issue is that you cannot plant grass when the yard is full of weeds. However, if you take too hard an approach killing the weeds — that is, with powerful antibiotics — you jeopardize the new grass, or in this case, the bacteria in the transplant. Solving that issue will be important as we consider whether this is effective or not.”
Dr. Beck added that there is still much to be learned from research into the gut microbiota. “I am hopeful with additional effort we will have answers soon.”
A version of this article appeared on Medscape.com.
, results of a new, randomized placebo-controlled trial show.
However, investigators discovered some interesting insights from the study, which they believe may help in designing future “improved, and hopefully successful, trials” with the intervention.
“Further studies — for example, through modified fecal microbiota transplantation approaches or bowel cleansing — are warranted,” they concluded.
The study was published online in JAMA Neurology.
Gut Dysfunction: An Early Symptom
Investigators led by Filip Scheperjans, MD, Helsinki University Hospital, Finland, explained that gut dysfunction is a prevalent, early symptom in Parkinson’s disease and is associated with more rapid disease progression.
Interventions targeting gut microbiota, such as FMT, have shown promising symptomatic, and potentially neuroprotective, effects in animal models of Parkinson’s disease.
Although several randomized clinical trials suggest efficacy of probiotics for Parkinson’s disease-related constipation, only limited clinical information on FMT is available.
In the current trial, 48 patients with Parkinson’s disease aged 35-75 years with mild to moderate symptoms and dysbiosis of fecal microbiota were randomized in a 2:1 ratio to receive FMT or placebo infused into the cecum via colonoscopy.
All patients had whole-bowel lavage starting the day before the colonoscopy. Fecal microbiota transplantation was administered as a single-dose and without antibiotic pretreatment.
Active treatment was a freeze-stored preparation of 30 g of feces from one of two donors who were healthy individuals without dysbiosis. The preparation was mixed with 150 mL of sterile physiologic saline and 20 mL of 85% glycerol for cryoprotection to improve viability of microbes. Placebo was the carrier solution alone, consisting of 180 mL of sterile physiologic saline and 20 mL of 85% glycerol.
The primary endpoint, a change in Parkinson’s disease symptoms as assessed on the Unified Parkinson’s Disease Rating Scale (UPDRS) at 6 months, did not differ between the two study groups.
Gastrointestinal adverse events were more frequent in the FMT group, occurring in 16 patients (53%) versus one patient (7%) in the placebo group. But no major safety concerns were observed.
Secondary outcomes and post hoc analyses showed a greater increase in dopaminergic medication, which may indicate faster disease progression, but also improvement in certain motor and nonmotor outcomes in the placebo group.
Microbiota changes were more pronounced after FMT, but dysbiosis status was reversed more frequently in the placebo group.
The researchers noted that the apparent futility in this trial is in contrast to several previous small clinical studies of fecal transplant that have suggested the potential for improvement of Parkinson’s disease symptoms.
In addition, encouraging results from the probiotics field suggest that an impact on motor and nonmotor Parkinson’s disease symptoms through gut microbiota manipulation is possible.
The researchers raised the possibility that the placebo procedure was not an inert comparator, given the relatively strong and sustained gut microbiota alteration and dysbiosis conversion observed in the placebo group, and suggested that the colonic cleansing procedure may also have had some beneficial effect.
“It seems possible that, after cleansing of a dysbiotic gut microbiota, recolonization leads to a more physiologic gut microbiota composition with symptom improvement in the placebo group. This warrants further exploration of modified fecal microbiota transplantation approaches and bowel cleansing in Parkinson’s disease,” they concluded.
Distinct Gut Microbiome
In an accompanying editorial, Timothy R. Sampson, PhD, assistant professor, Department of Cell Biology, Emory University School of Medicine, Atlanta, pointed out that dozens of independent studies have now demonstrated a distinct gut microbiome composition associated with Parkinson’s disease, and experimental data suggest that this has the capacity to incite inflammatory responses; degrade intestinal mucosa; and dysregulate a number of neuroactive and amyloidogenic molecules, which could contribute to the disease.
He noted that three other small placebo-controlled studies of fecal transplantation in Parkinson’s disease showed slightly more robust responses in the active treatment group, including improvements in UPDRS scores and gastrointestinal symptoms.
However, these studies tested different FMT procedures, including lyophilized oral capsules given at different dosing frequencies and either nasojejunal or colonic transfusion following a standard bowel preparation.
In addition, there is no consensus on pretransplant procedures, such as antibiotics or bowel clearance, and the choice of donor microbiome is probably essential, because there may be certain microbes required to shift the entire community, Dr. Sampson wrote.
Understanding how microbial contributions directly relate to Parkinson’s disease would identify individuals more likely to respond to peripheral interventions, and further exploration is needed to shed light on particular microbes that warrant targeting for either enrichment or depletion, he added.
“Despite a lack of primary end point efficacy in this latest study, in-depth comparison across these studies may reveal opportunities to refine fecal microbiota transplantation approaches. Together, these studies will continue to refine the hypothesis of a microbial contribution to Parkinson’s disease and reveal new therapeutic avenues,” Dr. Sampson concluded.
‘Planting Grass in a Yard Full of Weeds’
Commenting on the research, James Beck, PhD, chief scientific officer of the Parkinson’s Foundation, New York, said that whether FMT are helpful remains to be determined.
“The key question that needs to be solved is how to best perform these transplants. One issue is that you cannot plant grass when the yard is full of weeds. However, if you take too hard an approach killing the weeds — that is, with powerful antibiotics — you jeopardize the new grass, or in this case, the bacteria in the transplant. Solving that issue will be important as we consider whether this is effective or not.”
Dr. Beck added that there is still much to be learned from research into the gut microbiota. “I am hopeful with additional effort we will have answers soon.”
A version of this article appeared on Medscape.com.
FROM JAMA NEUROLOGY
New Parkinson’s Disease Gene Discovered
HELSINKI, FINLAND — , a discovery that experts believe will have important clinical implications in the not-too-distant future.
A variant in PMSF1, a proteasome regulator, was identified in 15 families from 13 countries around the world, with 22 affected individuals.
“These families were ethnically diverse, and in all of them, the variant in PMSF1 correlated with the neurologic phenotype. We know this is very clear cut — the genotype/phenotype correlation — with the patients carrying the missense mutation having ‘mild’ symptoms, while those with the progressive loss-of-function variant had the most severe phenotype,” she noted.
“Our findings unequivocally link defective PSMF1 to early-onset PD and neurodegeneration and suggest mitochondrial dysfunction as a mechanistic contributor,” study investigator Francesca Magrinelli, MD, PhD, of University College London (UCL) Queen Square Institute of Neurology, UCL, London, told delegates at the 2024 Congress of the European Academy of Neurology.
Managing Patient Expectations
Those “mildly” affected had an early-onset Parkinson’s disease starting between the second and fifth decade of life with pyramidal tract signs, dysphasia, psychiatric comorbidity, and early levodopa-induced dyskinesia.
In those with the intermediate type, Parkinson’s disease symptoms start in childhood and include, among other things, global hypokinesia, developmental delay, cerebellar signs, and in some, associated epilepsy.
In most cases, there was evidence on brain MRI of a hypoplasia of the corpus callosum, Dr. Magrinelli said. In the most severely affected individuals, there was perinatal lethality with neurologic manifestations.
While it may seem that the genetics of Parkinson’s disease is an academic exercise for the most part, it won’t be too much longer before it yields practical information that will inform how patients are treated, said Parkinson’s disease expert Christine Klein, MD, of the Institute of Neurogenetics and Department of Neurology, University of Lübeck, Helsinki, Finland.
The genetics of Parkinson’s disease are complicated, even within a single family. So, it’s very important to assess the pathogenicity of different variants, Dr. Klein noted.
“I am sure that you have all had a Parkinson’s disease [gene] panel back, and it says, ‘variant of uncertain significance.’ This is the worst thing that can happen. The lab does not know what it means. You don’t know what it means, and you don’t know what to tell the patient. So how do you get around this?”
Dr. Klein said that before conducting any genetic testing, clinicians should inform the patient that they may have a genetic variant of uncertain significance. It doesn’t solve the problem, but it does help physicians manage patient expectations.
Clinical Relevance on the Way?
While it may seem that all of the identified variants that predict Parkinson’s disease which, in addition to PSMF1, include the well-established LRRK2 and GBA1, may look the same, this is not true when patient history is taken into account, said Dr. Klein.
For example, age-of-onset of Parkinson’s disease can differ between identified variants, and this has led to “a paradigm change” whereby a purely genetic finding is called a disease.
This first occurred in Huntington’s disease, when researchers gave individuals at high genetic risk of developing the illness, but who currently had no clinical symptoms, the label of “Stage Zero disease.”
This is important to note “because if we get to the stage of having drugs that can slow down, or even prevent, progression to Parkinson’s disease, then it will be key to have patients we know are going to develop it to participate in clinical trials for such agents,” said Dr. Klein.
She cited the example of a family that she recently encountered that had genetic test results that showed variants of unknown significance, so Dr. Klein had the family’s samples sent to a specialized lab in Dundee, Scotland, for further analysis.
“The biochemists found that this variant was indeed pathogenic, and kinase-activating, so this is very helpful and very important because there are now clinical trials in Parkinson’s disease with kinase inhibitors,” she noted.
“If you think there is something else [over and above the finding of uncertain significance] in your Parkinson’s disease panel, and you are not happy with the genetic report, send it somewhere else,” Dr. Klein advised.
“We will see a lot more patients with genetic Parkinson’s disease in the future,” she predicted, while citing two recent preliminary clinical trials that have shown some promise in terms of neuroprotection in patients with early Parkinson’s disease.
“It remains to be seen whether there will be light at the end of the tunnel,” she said, but it may soon be possible to find treatments that delay, or even prevent, Parkinson’s disease onset.
Dr. Magrinelli reported receiving speaker’s honoraria from MJFF Edmond J. Safra Clinical Research Fellowship in Movement Disorders (Class of 2023), MJFF Edmond J. Safra Movement Disorders Research Career Development Award 2023 (Grant ID MJFF-023893), American Parkinson Disease Association (Research Grant 2024), and the David Blank Charitable Foundation. Dr. Klein reported being a medical advisor to Retromer Therapeutics, Takeda, and Centogene and speakers’ honoraria from Desitin and Bial.
A version of this article first appeared on Medscape.com.
HELSINKI, FINLAND — , a discovery that experts believe will have important clinical implications in the not-too-distant future.
A variant in PMSF1, a proteasome regulator, was identified in 15 families from 13 countries around the world, with 22 affected individuals.
“These families were ethnically diverse, and in all of them, the variant in PMSF1 correlated with the neurologic phenotype. We know this is very clear cut — the genotype/phenotype correlation — with the patients carrying the missense mutation having ‘mild’ symptoms, while those with the progressive loss-of-function variant had the most severe phenotype,” she noted.
“Our findings unequivocally link defective PSMF1 to early-onset PD and neurodegeneration and suggest mitochondrial dysfunction as a mechanistic contributor,” study investigator Francesca Magrinelli, MD, PhD, of University College London (UCL) Queen Square Institute of Neurology, UCL, London, told delegates at the 2024 Congress of the European Academy of Neurology.
Managing Patient Expectations
Those “mildly” affected had an early-onset Parkinson’s disease starting between the second and fifth decade of life with pyramidal tract signs, dysphasia, psychiatric comorbidity, and early levodopa-induced dyskinesia.
In those with the intermediate type, Parkinson’s disease symptoms start in childhood and include, among other things, global hypokinesia, developmental delay, cerebellar signs, and in some, associated epilepsy.
In most cases, there was evidence on brain MRI of a hypoplasia of the corpus callosum, Dr. Magrinelli said. In the most severely affected individuals, there was perinatal lethality with neurologic manifestations.
While it may seem that the genetics of Parkinson’s disease is an academic exercise for the most part, it won’t be too much longer before it yields practical information that will inform how patients are treated, said Parkinson’s disease expert Christine Klein, MD, of the Institute of Neurogenetics and Department of Neurology, University of Lübeck, Helsinki, Finland.
The genetics of Parkinson’s disease are complicated, even within a single family. So, it’s very important to assess the pathogenicity of different variants, Dr. Klein noted.
“I am sure that you have all had a Parkinson’s disease [gene] panel back, and it says, ‘variant of uncertain significance.’ This is the worst thing that can happen. The lab does not know what it means. You don’t know what it means, and you don’t know what to tell the patient. So how do you get around this?”
Dr. Klein said that before conducting any genetic testing, clinicians should inform the patient that they may have a genetic variant of uncertain significance. It doesn’t solve the problem, but it does help physicians manage patient expectations.
Clinical Relevance on the Way?
While it may seem that all of the identified variants that predict Parkinson’s disease which, in addition to PSMF1, include the well-established LRRK2 and GBA1, may look the same, this is not true when patient history is taken into account, said Dr. Klein.
For example, age-of-onset of Parkinson’s disease can differ between identified variants, and this has led to “a paradigm change” whereby a purely genetic finding is called a disease.
This first occurred in Huntington’s disease, when researchers gave individuals at high genetic risk of developing the illness, but who currently had no clinical symptoms, the label of “Stage Zero disease.”
This is important to note “because if we get to the stage of having drugs that can slow down, or even prevent, progression to Parkinson’s disease, then it will be key to have patients we know are going to develop it to participate in clinical trials for such agents,” said Dr. Klein.
She cited the example of a family that she recently encountered that had genetic test results that showed variants of unknown significance, so Dr. Klein had the family’s samples sent to a specialized lab in Dundee, Scotland, for further analysis.
“The biochemists found that this variant was indeed pathogenic, and kinase-activating, so this is very helpful and very important because there are now clinical trials in Parkinson’s disease with kinase inhibitors,” she noted.
“If you think there is something else [over and above the finding of uncertain significance] in your Parkinson’s disease panel, and you are not happy with the genetic report, send it somewhere else,” Dr. Klein advised.
“We will see a lot more patients with genetic Parkinson’s disease in the future,” she predicted, while citing two recent preliminary clinical trials that have shown some promise in terms of neuroprotection in patients with early Parkinson’s disease.
“It remains to be seen whether there will be light at the end of the tunnel,” she said, but it may soon be possible to find treatments that delay, or even prevent, Parkinson’s disease onset.
Dr. Magrinelli reported receiving speaker’s honoraria from MJFF Edmond J. Safra Clinical Research Fellowship in Movement Disorders (Class of 2023), MJFF Edmond J. Safra Movement Disorders Research Career Development Award 2023 (Grant ID MJFF-023893), American Parkinson Disease Association (Research Grant 2024), and the David Blank Charitable Foundation. Dr. Klein reported being a medical advisor to Retromer Therapeutics, Takeda, and Centogene and speakers’ honoraria from Desitin and Bial.
A version of this article first appeared on Medscape.com.
HELSINKI, FINLAND — , a discovery that experts believe will have important clinical implications in the not-too-distant future.
A variant in PMSF1, a proteasome regulator, was identified in 15 families from 13 countries around the world, with 22 affected individuals.
“These families were ethnically diverse, and in all of them, the variant in PMSF1 correlated with the neurologic phenotype. We know this is very clear cut — the genotype/phenotype correlation — with the patients carrying the missense mutation having ‘mild’ symptoms, while those with the progressive loss-of-function variant had the most severe phenotype,” she noted.
“Our findings unequivocally link defective PSMF1 to early-onset PD and neurodegeneration and suggest mitochondrial dysfunction as a mechanistic contributor,” study investigator Francesca Magrinelli, MD, PhD, of University College London (UCL) Queen Square Institute of Neurology, UCL, London, told delegates at the 2024 Congress of the European Academy of Neurology.
Managing Patient Expectations
Those “mildly” affected had an early-onset Parkinson’s disease starting between the second and fifth decade of life with pyramidal tract signs, dysphasia, psychiatric comorbidity, and early levodopa-induced dyskinesia.
In those with the intermediate type, Parkinson’s disease symptoms start in childhood and include, among other things, global hypokinesia, developmental delay, cerebellar signs, and in some, associated epilepsy.
In most cases, there was evidence on brain MRI of a hypoplasia of the corpus callosum, Dr. Magrinelli said. In the most severely affected individuals, there was perinatal lethality with neurologic manifestations.
While it may seem that the genetics of Parkinson’s disease is an academic exercise for the most part, it won’t be too much longer before it yields practical information that will inform how patients are treated, said Parkinson’s disease expert Christine Klein, MD, of the Institute of Neurogenetics and Department of Neurology, University of Lübeck, Helsinki, Finland.
The genetics of Parkinson’s disease are complicated, even within a single family. So, it’s very important to assess the pathogenicity of different variants, Dr. Klein noted.
“I am sure that you have all had a Parkinson’s disease [gene] panel back, and it says, ‘variant of uncertain significance.’ This is the worst thing that can happen. The lab does not know what it means. You don’t know what it means, and you don’t know what to tell the patient. So how do you get around this?”
Dr. Klein said that before conducting any genetic testing, clinicians should inform the patient that they may have a genetic variant of uncertain significance. It doesn’t solve the problem, but it does help physicians manage patient expectations.
Clinical Relevance on the Way?
While it may seem that all of the identified variants that predict Parkinson’s disease which, in addition to PSMF1, include the well-established LRRK2 and GBA1, may look the same, this is not true when patient history is taken into account, said Dr. Klein.
For example, age-of-onset of Parkinson’s disease can differ between identified variants, and this has led to “a paradigm change” whereby a purely genetic finding is called a disease.
This first occurred in Huntington’s disease, when researchers gave individuals at high genetic risk of developing the illness, but who currently had no clinical symptoms, the label of “Stage Zero disease.”
This is important to note “because if we get to the stage of having drugs that can slow down, or even prevent, progression to Parkinson’s disease, then it will be key to have patients we know are going to develop it to participate in clinical trials for such agents,” said Dr. Klein.
She cited the example of a family that she recently encountered that had genetic test results that showed variants of unknown significance, so Dr. Klein had the family’s samples sent to a specialized lab in Dundee, Scotland, for further analysis.
“The biochemists found that this variant was indeed pathogenic, and kinase-activating, so this is very helpful and very important because there are now clinical trials in Parkinson’s disease with kinase inhibitors,” she noted.
“If you think there is something else [over and above the finding of uncertain significance] in your Parkinson’s disease panel, and you are not happy with the genetic report, send it somewhere else,” Dr. Klein advised.
“We will see a lot more patients with genetic Parkinson’s disease in the future,” she predicted, while citing two recent preliminary clinical trials that have shown some promise in terms of neuroprotection in patients with early Parkinson’s disease.
“It remains to be seen whether there will be light at the end of the tunnel,” she said, but it may soon be possible to find treatments that delay, or even prevent, Parkinson’s disease onset.
Dr. Magrinelli reported receiving speaker’s honoraria from MJFF Edmond J. Safra Clinical Research Fellowship in Movement Disorders (Class of 2023), MJFF Edmond J. Safra Movement Disorders Research Career Development Award 2023 (Grant ID MJFF-023893), American Parkinson Disease Association (Research Grant 2024), and the David Blank Charitable Foundation. Dr. Klein reported being a medical advisor to Retromer Therapeutics, Takeda, and Centogene and speakers’ honoraria from Desitin and Bial.
A version of this article first appeared on Medscape.com.
FROM EAN 2024
Change in Clinical Definition of Parkinson’s Triggers Debate
Parkinson’s disease (PD) and dementia with Lewy bodies are currently defined by clinical features, which can be heterogeneous and do not capture the presymptomatic phase of neurodegeneration.
Recent advances have enabled the detection of misfolded and aggregated alpha-synuclein protein (synucleinopathy) — a key pathologic feature of these diseases — allowing for earlier and more accurate diagnosis. This has led two international research groups to propose a major shift from a clinical to a biological definition of the disease.
Both groups emphasized the detection of alpha-synuclein through recently developed seed amplification assays as a key diagnostic and staging tool, although they differ in their approaches and criteria.
NSD-ISS
NSD is defined by the presence during life of pathologic neuronal alpha-synuclein (S, the first biological anchor) in cerebrospinal fluid (CSF), regardless of the presence of any specific clinical syndrome. Individuals with pathologic neuronal alpha-synuclein aggregates are at a high risk for dopaminergic neuronal dysfunction (D, the second key biological anchor).
Dr. Simuni and colleagues also proposed the NSD integrated staging system (NSD-ISS) rooted in the S and D biological anchors coupled with the degree of functional impairment caused by clinical signs or symptoms.
Stages 0-1 occur without signs or symptoms and are defined by the presence of pathogenic variants in the SNCA gene (stage 0), S alone (stage 1A), or S and D (stage 1B).
The presence of clinical manifestations marks the transition to stage 2 and beyond, with stage 2 characterized by subtle signs or symptoms but without functional impairment. Stages 2B-6 require both S and D and stage-specific increases in functional impairment.
“An advantage of the NSD-ISS will be to reduce heterogeneity in clinical trials by requiring biological consistency within the study cohort rather than identifying study participants on the basis of clinical criteria for Parkinson’s disease and dementia with Lewy bodies,” Dr. Simuni and colleagues pointed out in a position paper describing the NSD-ISS published online earlier this year in The Lancet Neurology.
The NSD-ISS will “evolve to include the incorporation of data-driven definitions of stage-specific functional anchors and additional biomarkers as they emerge and are validated.”
For now, the NSD-ISS is intended for research use only and not in the clinic.
The SynNeurGe Research Diagnostic Criteria
Separately, a team led by Anthony Lang, MD, with the Krembil Brain Institute at Toronto Western Hospital, Toronto, Ontario, Canada, proposed the SynNeurGe biological classification of PD.
Described in a companion paper published online in The Lancet Neurology, their “S-N-G” classification emphasizes the important interactions between three biological factors that contribute to disease: The presence or absence of pathologic alpha-synuclein (S) in tissues or CSF, an evidence of underlying neurodegeneration (N) defined by neuroimaging procedures, and the documentation of pathogenic gene variants (G) that cause or strongly predispose to PD.
These three components link to a clinical component, defined either by a single high-specificity clinical feature or by multiple lower-specificity clinical features.
As with the NSD-ISS, the SynNeurGe model is intended for research purposes only and is not ready for immediate application in the clinic.
Both groups acknowledged the need for studies to test and validate the proposed classification systems.
Caveats, Cautionary Notes
Adopting a biological definition of PD would represent a shift as the field has prompted considerable discussion and healthy debate.
Commenting for this news organization, James Beck, PhD, chief scientific officer at the Parkinson’s Foundation, said the principle behind the proposed classifications is where “the field needs to go.”
“Right now, people with Parkinson’s take too long to get a confirmed diagnosis of their disease, and despite best efforts, clinicians can get it wrong, not diagnosing people or maybe misdiagnosing people,” Dr. Beck said. “Moving to a biological basis, where we have better certainty, is going to be really important.”
Beck noted that the NSD-ISS “goes all in on alpha-synuclein,” which does play a big role in PD, but added, “I don’t know if I want to declare a winner after the first heat. There are other biomarkers that are coming to fruition but still need validation, and alpha-synuclein may be just one of many to help determine whether someone has Parkinson’s disease or not.”
Un Kang, MD, director of translational research at the Fresco Institute for Parkinson’s & Movement Disorders at NYU Langone Health, New York City, told this news organization that alpha-synuclein has “very high diagnostic accuracy” but cautioned that the adoption of a biological definition for PD would not usurp a clinical diagnosis.
“We need both,” Dr. Kang said. “But knowing the underlying pathology is important for earlier diagnosis and testing of potential therapies to treat the molecular pathology. If a patient doesn’t have abnormal synuclein, you may be treating the wrong disease.”
The coauthors of recent JAMA Neurology perspective said the biological definitions are “exciting, but there is “wisdom” in tapping the brakes when attempting to establish a biological definition and classification system for PD.
“Although these two proposals represent significant steps forward, a sprint toward the finish line may not be wise,” wrote Njideka U. Okubadejo, MD, with University of Lagos, Nigeria; Joseph Jankovic, MD, with Baylor College of Medicine, Houston; and Michael S. Okun, MD, with University of Florida Health, Gainesville, Florida.
“A process that embraces inclusivity and weaves in evolving technological advancements will be important. Who benefits if implementation of a biologically based staging system for PD is hurried?” they continued.
The proposals rely heavily on alpha-synuclein assays, they noted, which currently require subjective interpretation and lack extensive validation. They also worry that the need for expensive and, in some regions, unattainable biological fluids (CSF) or imaging studies (dopamine transporter scan) may limit global access to both PD trials and future therapeutics.
They also worry about retiring the name Parkinson’s disease.
“Beyond the historical importance of the term Parkinson disease, any classification that proposes abandoning the two words in either clinical or research descriptions could have unintended global repercussions,” Dr. Okubadejo, Dr. Jankovic, and Dr. Okun cautioned.
Dr. Beck told this news organization he’s spoken to clinicians at meetings about this and “no one really likes the idea” of retiring the term Parkinson’s disease.
Frederick Ketchum, MD, and Nathaniel Chin, MD, with University of Wisconsin–Madison, worry about the “lived” experience of the asymptomatic patient after receiving a biological diagnosis.
“Biological diagnosis might enable effective prognostication and treatment in the future but will substantially change the experience of illness for patients now as new frameworks are slowly adopted and knowledge is gained,” they said in a correspondence in The Lancet Neurology.
“Understanding and addressing this lived experience remains a core task for health professionals and must be made central as we begin an era in which neurological diseases are redefined on a biological basis,” Dr. Ketchum and Dr. Chin advised.
A complete list of agencies that supported this work and author disclosures are available with the original articles. Dr. Beck and Dr. Kang had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Parkinson’s disease (PD) and dementia with Lewy bodies are currently defined by clinical features, which can be heterogeneous and do not capture the presymptomatic phase of neurodegeneration.
Recent advances have enabled the detection of misfolded and aggregated alpha-synuclein protein (synucleinopathy) — a key pathologic feature of these diseases — allowing for earlier and more accurate diagnosis. This has led two international research groups to propose a major shift from a clinical to a biological definition of the disease.
Both groups emphasized the detection of alpha-synuclein through recently developed seed amplification assays as a key diagnostic and staging tool, although they differ in their approaches and criteria.
NSD-ISS
NSD is defined by the presence during life of pathologic neuronal alpha-synuclein (S, the first biological anchor) in cerebrospinal fluid (CSF), regardless of the presence of any specific clinical syndrome. Individuals with pathologic neuronal alpha-synuclein aggregates are at a high risk for dopaminergic neuronal dysfunction (D, the second key biological anchor).
Dr. Simuni and colleagues also proposed the NSD integrated staging system (NSD-ISS) rooted in the S and D biological anchors coupled with the degree of functional impairment caused by clinical signs or symptoms.
Stages 0-1 occur without signs or symptoms and are defined by the presence of pathogenic variants in the SNCA gene (stage 0), S alone (stage 1A), or S and D (stage 1B).
The presence of clinical manifestations marks the transition to stage 2 and beyond, with stage 2 characterized by subtle signs or symptoms but without functional impairment. Stages 2B-6 require both S and D and stage-specific increases in functional impairment.
“An advantage of the NSD-ISS will be to reduce heterogeneity in clinical trials by requiring biological consistency within the study cohort rather than identifying study participants on the basis of clinical criteria for Parkinson’s disease and dementia with Lewy bodies,” Dr. Simuni and colleagues pointed out in a position paper describing the NSD-ISS published online earlier this year in The Lancet Neurology.
The NSD-ISS will “evolve to include the incorporation of data-driven definitions of stage-specific functional anchors and additional biomarkers as they emerge and are validated.”
For now, the NSD-ISS is intended for research use only and not in the clinic.
The SynNeurGe Research Diagnostic Criteria
Separately, a team led by Anthony Lang, MD, with the Krembil Brain Institute at Toronto Western Hospital, Toronto, Ontario, Canada, proposed the SynNeurGe biological classification of PD.
Described in a companion paper published online in The Lancet Neurology, their “S-N-G” classification emphasizes the important interactions between three biological factors that contribute to disease: The presence or absence of pathologic alpha-synuclein (S) in tissues or CSF, an evidence of underlying neurodegeneration (N) defined by neuroimaging procedures, and the documentation of pathogenic gene variants (G) that cause or strongly predispose to PD.
These three components link to a clinical component, defined either by a single high-specificity clinical feature or by multiple lower-specificity clinical features.
As with the NSD-ISS, the SynNeurGe model is intended for research purposes only and is not ready for immediate application in the clinic.
Both groups acknowledged the need for studies to test and validate the proposed classification systems.
Caveats, Cautionary Notes
Adopting a biological definition of PD would represent a shift as the field has prompted considerable discussion and healthy debate.
Commenting for this news organization, James Beck, PhD, chief scientific officer at the Parkinson’s Foundation, said the principle behind the proposed classifications is where “the field needs to go.”
“Right now, people with Parkinson’s take too long to get a confirmed diagnosis of their disease, and despite best efforts, clinicians can get it wrong, not diagnosing people or maybe misdiagnosing people,” Dr. Beck said. “Moving to a biological basis, where we have better certainty, is going to be really important.”
Beck noted that the NSD-ISS “goes all in on alpha-synuclein,” which does play a big role in PD, but added, “I don’t know if I want to declare a winner after the first heat. There are other biomarkers that are coming to fruition but still need validation, and alpha-synuclein may be just one of many to help determine whether someone has Parkinson’s disease or not.”
Un Kang, MD, director of translational research at the Fresco Institute for Parkinson’s & Movement Disorders at NYU Langone Health, New York City, told this news organization that alpha-synuclein has “very high diagnostic accuracy” but cautioned that the adoption of a biological definition for PD would not usurp a clinical diagnosis.
“We need both,” Dr. Kang said. “But knowing the underlying pathology is important for earlier diagnosis and testing of potential therapies to treat the molecular pathology. If a patient doesn’t have abnormal synuclein, you may be treating the wrong disease.”
The coauthors of recent JAMA Neurology perspective said the biological definitions are “exciting, but there is “wisdom” in tapping the brakes when attempting to establish a biological definition and classification system for PD.
“Although these two proposals represent significant steps forward, a sprint toward the finish line may not be wise,” wrote Njideka U. Okubadejo, MD, with University of Lagos, Nigeria; Joseph Jankovic, MD, with Baylor College of Medicine, Houston; and Michael S. Okun, MD, with University of Florida Health, Gainesville, Florida.
“A process that embraces inclusivity and weaves in evolving technological advancements will be important. Who benefits if implementation of a biologically based staging system for PD is hurried?” they continued.
The proposals rely heavily on alpha-synuclein assays, they noted, which currently require subjective interpretation and lack extensive validation. They also worry that the need for expensive and, in some regions, unattainable biological fluids (CSF) or imaging studies (dopamine transporter scan) may limit global access to both PD trials and future therapeutics.
They also worry about retiring the name Parkinson’s disease.
“Beyond the historical importance of the term Parkinson disease, any classification that proposes abandoning the two words in either clinical or research descriptions could have unintended global repercussions,” Dr. Okubadejo, Dr. Jankovic, and Dr. Okun cautioned.
Dr. Beck told this news organization he’s spoken to clinicians at meetings about this and “no one really likes the idea” of retiring the term Parkinson’s disease.
Frederick Ketchum, MD, and Nathaniel Chin, MD, with University of Wisconsin–Madison, worry about the “lived” experience of the asymptomatic patient after receiving a biological diagnosis.
“Biological diagnosis might enable effective prognostication and treatment in the future but will substantially change the experience of illness for patients now as new frameworks are slowly adopted and knowledge is gained,” they said in a correspondence in The Lancet Neurology.
“Understanding and addressing this lived experience remains a core task for health professionals and must be made central as we begin an era in which neurological diseases are redefined on a biological basis,” Dr. Ketchum and Dr. Chin advised.
A complete list of agencies that supported this work and author disclosures are available with the original articles. Dr. Beck and Dr. Kang had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Parkinson’s disease (PD) and dementia with Lewy bodies are currently defined by clinical features, which can be heterogeneous and do not capture the presymptomatic phase of neurodegeneration.
Recent advances have enabled the detection of misfolded and aggregated alpha-synuclein protein (synucleinopathy) — a key pathologic feature of these diseases — allowing for earlier and more accurate diagnosis. This has led two international research groups to propose a major shift from a clinical to a biological definition of the disease.
Both groups emphasized the detection of alpha-synuclein through recently developed seed amplification assays as a key diagnostic and staging tool, although they differ in their approaches and criteria.
NSD-ISS
NSD is defined by the presence during life of pathologic neuronal alpha-synuclein (S, the first biological anchor) in cerebrospinal fluid (CSF), regardless of the presence of any specific clinical syndrome. Individuals with pathologic neuronal alpha-synuclein aggregates are at a high risk for dopaminergic neuronal dysfunction (D, the second key biological anchor).
Dr. Simuni and colleagues also proposed the NSD integrated staging system (NSD-ISS) rooted in the S and D biological anchors coupled with the degree of functional impairment caused by clinical signs or symptoms.
Stages 0-1 occur without signs or symptoms and are defined by the presence of pathogenic variants in the SNCA gene (stage 0), S alone (stage 1A), or S and D (stage 1B).
The presence of clinical manifestations marks the transition to stage 2 and beyond, with stage 2 characterized by subtle signs or symptoms but without functional impairment. Stages 2B-6 require both S and D and stage-specific increases in functional impairment.
“An advantage of the NSD-ISS will be to reduce heterogeneity in clinical trials by requiring biological consistency within the study cohort rather than identifying study participants on the basis of clinical criteria for Parkinson’s disease and dementia with Lewy bodies,” Dr. Simuni and colleagues pointed out in a position paper describing the NSD-ISS published online earlier this year in The Lancet Neurology.
The NSD-ISS will “evolve to include the incorporation of data-driven definitions of stage-specific functional anchors and additional biomarkers as they emerge and are validated.”
For now, the NSD-ISS is intended for research use only and not in the clinic.
The SynNeurGe Research Diagnostic Criteria
Separately, a team led by Anthony Lang, MD, with the Krembil Brain Institute at Toronto Western Hospital, Toronto, Ontario, Canada, proposed the SynNeurGe biological classification of PD.
Described in a companion paper published online in The Lancet Neurology, their “S-N-G” classification emphasizes the important interactions between three biological factors that contribute to disease: The presence or absence of pathologic alpha-synuclein (S) in tissues or CSF, an evidence of underlying neurodegeneration (N) defined by neuroimaging procedures, and the documentation of pathogenic gene variants (G) that cause or strongly predispose to PD.
These three components link to a clinical component, defined either by a single high-specificity clinical feature or by multiple lower-specificity clinical features.
As with the NSD-ISS, the SynNeurGe model is intended for research purposes only and is not ready for immediate application in the clinic.
Both groups acknowledged the need for studies to test and validate the proposed classification systems.
Caveats, Cautionary Notes
Adopting a biological definition of PD would represent a shift as the field has prompted considerable discussion and healthy debate.
Commenting for this news organization, James Beck, PhD, chief scientific officer at the Parkinson’s Foundation, said the principle behind the proposed classifications is where “the field needs to go.”
“Right now, people with Parkinson’s take too long to get a confirmed diagnosis of their disease, and despite best efforts, clinicians can get it wrong, not diagnosing people or maybe misdiagnosing people,” Dr. Beck said. “Moving to a biological basis, where we have better certainty, is going to be really important.”
Beck noted that the NSD-ISS “goes all in on alpha-synuclein,” which does play a big role in PD, but added, “I don’t know if I want to declare a winner after the first heat. There are other biomarkers that are coming to fruition but still need validation, and alpha-synuclein may be just one of many to help determine whether someone has Parkinson’s disease or not.”
Un Kang, MD, director of translational research at the Fresco Institute for Parkinson’s & Movement Disorders at NYU Langone Health, New York City, told this news organization that alpha-synuclein has “very high diagnostic accuracy” but cautioned that the adoption of a biological definition for PD would not usurp a clinical diagnosis.
“We need both,” Dr. Kang said. “But knowing the underlying pathology is important for earlier diagnosis and testing of potential therapies to treat the molecular pathology. If a patient doesn’t have abnormal synuclein, you may be treating the wrong disease.”
The coauthors of recent JAMA Neurology perspective said the biological definitions are “exciting, but there is “wisdom” in tapping the brakes when attempting to establish a biological definition and classification system for PD.
“Although these two proposals represent significant steps forward, a sprint toward the finish line may not be wise,” wrote Njideka U. Okubadejo, MD, with University of Lagos, Nigeria; Joseph Jankovic, MD, with Baylor College of Medicine, Houston; and Michael S. Okun, MD, with University of Florida Health, Gainesville, Florida.
“A process that embraces inclusivity and weaves in evolving technological advancements will be important. Who benefits if implementation of a biologically based staging system for PD is hurried?” they continued.
The proposals rely heavily on alpha-synuclein assays, they noted, which currently require subjective interpretation and lack extensive validation. They also worry that the need for expensive and, in some regions, unattainable biological fluids (CSF) or imaging studies (dopamine transporter scan) may limit global access to both PD trials and future therapeutics.
They also worry about retiring the name Parkinson’s disease.
“Beyond the historical importance of the term Parkinson disease, any classification that proposes abandoning the two words in either clinical or research descriptions could have unintended global repercussions,” Dr. Okubadejo, Dr. Jankovic, and Dr. Okun cautioned.
Dr. Beck told this news organization he’s spoken to clinicians at meetings about this and “no one really likes the idea” of retiring the term Parkinson’s disease.
Frederick Ketchum, MD, and Nathaniel Chin, MD, with University of Wisconsin–Madison, worry about the “lived” experience of the asymptomatic patient after receiving a biological diagnosis.
“Biological diagnosis might enable effective prognostication and treatment in the future but will substantially change the experience of illness for patients now as new frameworks are slowly adopted and knowledge is gained,” they said in a correspondence in The Lancet Neurology.
“Understanding and addressing this lived experience remains a core task for health professionals and must be made central as we begin an era in which neurological diseases are redefined on a biological basis,” Dr. Ketchum and Dr. Chin advised.
A complete list of agencies that supported this work and author disclosures are available with the original articles. Dr. Beck and Dr. Kang had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Another Social Media Snowball
Recently, the British Journal of General Practice published a paper that claimed that anxiety may be a prodromal feature of Parkinson’s disease). That news was widely picked up and spread.
The researchers certainly have some interesting data, but this sort of article, once enough general and social media websites get a hold of it, is bound to cause panic in the streets. And phone calls to my office.
An anxious-by-nature friend even emailed me the link with a laconic “Well, I’m screwed” in the subject line.
Is there a correlation between Parkinson’s disease and anxiety? Probably. Any of us practicing neurology have seen it. Some of it is likely from the anxiety of the situation, but the biochemical changes brought by the disease are also likely a big part.
But does that mean everyone with anxiety has Parkinson’s disease? Of course not. Anxiety is common, probably more common in our current era than ever before (this is why I tell patients not to watch the news and to avoid social media — they’re bad for your sanity and blood pressure).
Stories like this, once they start getting forwarded on Facebook (or another social media outlet), only raise anxiety, which results in more forwarding, and the snowball begins rolling downhill before crashing into my office (obviously this is a figure of speech, as it’s July in Phoenix).
The research is interesting. The point is valid. But the leaps the public makes are ... problematic. It’s only a matter of time before someone comes in demanding a DaT scan because they’re anxious. At $4K a test, that’s not happening.
Which raises anxiety all around.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
Recently, the British Journal of General Practice published a paper that claimed that anxiety may be a prodromal feature of Parkinson’s disease). That news was widely picked up and spread.
The researchers certainly have some interesting data, but this sort of article, once enough general and social media websites get a hold of it, is bound to cause panic in the streets. And phone calls to my office.
An anxious-by-nature friend even emailed me the link with a laconic “Well, I’m screwed” in the subject line.
Is there a correlation between Parkinson’s disease and anxiety? Probably. Any of us practicing neurology have seen it. Some of it is likely from the anxiety of the situation, but the biochemical changes brought by the disease are also likely a big part.
But does that mean everyone with anxiety has Parkinson’s disease? Of course not. Anxiety is common, probably more common in our current era than ever before (this is why I tell patients not to watch the news and to avoid social media — they’re bad for your sanity and blood pressure).
Stories like this, once they start getting forwarded on Facebook (or another social media outlet), only raise anxiety, which results in more forwarding, and the snowball begins rolling downhill before crashing into my office (obviously this is a figure of speech, as it’s July in Phoenix).
The research is interesting. The point is valid. But the leaps the public makes are ... problematic. It’s only a matter of time before someone comes in demanding a DaT scan because they’re anxious. At $4K a test, that’s not happening.
Which raises anxiety all around.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
Recently, the British Journal of General Practice published a paper that claimed that anxiety may be a prodromal feature of Parkinson’s disease). That news was widely picked up and spread.
The researchers certainly have some interesting data, but this sort of article, once enough general and social media websites get a hold of it, is bound to cause panic in the streets. And phone calls to my office.
An anxious-by-nature friend even emailed me the link with a laconic “Well, I’m screwed” in the subject line.
Is there a correlation between Parkinson’s disease and anxiety? Probably. Any of us practicing neurology have seen it. Some of it is likely from the anxiety of the situation, but the biochemical changes brought by the disease are also likely a big part.
But does that mean everyone with anxiety has Parkinson’s disease? Of course not. Anxiety is common, probably more common in our current era than ever before (this is why I tell patients not to watch the news and to avoid social media — they’re bad for your sanity and blood pressure).
Stories like this, once they start getting forwarded on Facebook (or another social media outlet), only raise anxiety, which results in more forwarding, and the snowball begins rolling downhill before crashing into my office (obviously this is a figure of speech, as it’s July in Phoenix).
The research is interesting. The point is valid. But the leaps the public makes are ... problematic. It’s only a matter of time before someone comes in demanding a DaT scan because they’re anxious. At $4K a test, that’s not happening.
Which raises anxiety all around.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
Is Anxiety a Prodromal Feature of Parkinson’s Disease?
new research suggested.
Investigators drew on 10-year data from primary care registry to compare almost 110,000 patients who developed anxiety after the age of 50 years with close to 900,000 matched controls without anxiety.
After adjusting for a variety of sociodemographic, lifestyle, psychiatric, and neurological factors, they found that the risk of developing Parkinson’s disease was double in those with anxiety, compared with controls.
“Anxiety is known to be a feature of the early stages of Parkinson’s disease, but prior to our study, the prospective risk of Parkinson’s in those over the age of 50 with new-onset anxiety was unknown,” colead author Juan Bazo Alvarez, a senior research fellow in the Division of Epidemiology and Health at University College London, London, England, said in a news release.
The study was published online in the British Journal of General Practice.
The presence of anxiety is increased in prodromal Parkinson’s disease, but the prospective risk for Parkinson’s disease in those aged 50 years or older with new-onset anxiety was largely unknown.
Investigators analyzed data from a large UK primary care dataset that includes all people aged between 50 and 99 years who were registered with a participating practice from Jan. 1, 2008, to Dec. 31, 2018.
They identified 109,435 people (35% men) with more than one anxiety record in the database but no previous record of anxiety for 1 year or more and 878,256 people (37% men) with no history of anxiety (control group).
Features of Parkinson’s disease such as sleep problems, depression, tremor, and impaired balance were then tracked from the point of the anxiety diagnosis until 1 year before the Parkinson’s disease diagnosis.
Among those with anxiety, 331 developed Parkinson’s disease during the follow-up period, with a median time to diagnosis of 4.9 years after the first recorded episode of anxiety.
The incidence of Parkinson’s disease was 1.2 per 1000 person-years (95% CI, 0.92-1.13) in those with anxiety versus 0.49 (95% CI, 0.47-0.52) in those without anxiety.
After adjustment for age, sex, social deprivation, lifestyle factors, severe mental illness, head trauma, and dementia, the risk for Parkinson’s disease was double in those with anxiety, compared with the non-anxiety group (hazard ratio, 2.1; 95% CI, 1.9-2.4).
Individuals without anxiety also developed Parkinson’s disease later than those with anxiety.
The researchers identified specific symptoms that were associated with later development of Parkinson’s disease in those with anxiety, including depression, sleep disturbance, fatigue, and cognitive impairment, among other symptoms.
“The results suggest that there is a strong association between anxiety and diagnosis of Parkinson’s disease in patients aged over 50 years who present with a new diagnosis of anxiety,” the authors wrote. “This provides evidence for anxiety as a prodromal presentation of Parkinson’s disease.”
Future research “should explore anxiety in relation to other prodromal symptoms and how this symptom complex is associated with the incidence of Parkinson’s disease,” the researchers wrote. Doing so “may lead to earlier diagnosis and better management of Parkinson’s disease.”
This study was funded by the European Union. Specific authors received funding from the National Institute for Health and Care Research and the Alzheimer’s Society Clinical Training Fellowship program. The authors declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggested.
Investigators drew on 10-year data from primary care registry to compare almost 110,000 patients who developed anxiety after the age of 50 years with close to 900,000 matched controls without anxiety.
After adjusting for a variety of sociodemographic, lifestyle, psychiatric, and neurological factors, they found that the risk of developing Parkinson’s disease was double in those with anxiety, compared with controls.
“Anxiety is known to be a feature of the early stages of Parkinson’s disease, but prior to our study, the prospective risk of Parkinson’s in those over the age of 50 with new-onset anxiety was unknown,” colead author Juan Bazo Alvarez, a senior research fellow in the Division of Epidemiology and Health at University College London, London, England, said in a news release.
The study was published online in the British Journal of General Practice.
The presence of anxiety is increased in prodromal Parkinson’s disease, but the prospective risk for Parkinson’s disease in those aged 50 years or older with new-onset anxiety was largely unknown.
Investigators analyzed data from a large UK primary care dataset that includes all people aged between 50 and 99 years who were registered with a participating practice from Jan. 1, 2008, to Dec. 31, 2018.
They identified 109,435 people (35% men) with more than one anxiety record in the database but no previous record of anxiety for 1 year or more and 878,256 people (37% men) with no history of anxiety (control group).
Features of Parkinson’s disease such as sleep problems, depression, tremor, and impaired balance were then tracked from the point of the anxiety diagnosis until 1 year before the Parkinson’s disease diagnosis.
Among those with anxiety, 331 developed Parkinson’s disease during the follow-up period, with a median time to diagnosis of 4.9 years after the first recorded episode of anxiety.
The incidence of Parkinson’s disease was 1.2 per 1000 person-years (95% CI, 0.92-1.13) in those with anxiety versus 0.49 (95% CI, 0.47-0.52) in those without anxiety.
After adjustment for age, sex, social deprivation, lifestyle factors, severe mental illness, head trauma, and dementia, the risk for Parkinson’s disease was double in those with anxiety, compared with the non-anxiety group (hazard ratio, 2.1; 95% CI, 1.9-2.4).
Individuals without anxiety also developed Parkinson’s disease later than those with anxiety.
The researchers identified specific symptoms that were associated with later development of Parkinson’s disease in those with anxiety, including depression, sleep disturbance, fatigue, and cognitive impairment, among other symptoms.
“The results suggest that there is a strong association between anxiety and diagnosis of Parkinson’s disease in patients aged over 50 years who present with a new diagnosis of anxiety,” the authors wrote. “This provides evidence for anxiety as a prodromal presentation of Parkinson’s disease.”
Future research “should explore anxiety in relation to other prodromal symptoms and how this symptom complex is associated with the incidence of Parkinson’s disease,” the researchers wrote. Doing so “may lead to earlier diagnosis and better management of Parkinson’s disease.”
This study was funded by the European Union. Specific authors received funding from the National Institute for Health and Care Research and the Alzheimer’s Society Clinical Training Fellowship program. The authors declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggested.
Investigators drew on 10-year data from primary care registry to compare almost 110,000 patients who developed anxiety after the age of 50 years with close to 900,000 matched controls without anxiety.
After adjusting for a variety of sociodemographic, lifestyle, psychiatric, and neurological factors, they found that the risk of developing Parkinson’s disease was double in those with anxiety, compared with controls.
“Anxiety is known to be a feature of the early stages of Parkinson’s disease, but prior to our study, the prospective risk of Parkinson’s in those over the age of 50 with new-onset anxiety was unknown,” colead author Juan Bazo Alvarez, a senior research fellow in the Division of Epidemiology and Health at University College London, London, England, said in a news release.
The study was published online in the British Journal of General Practice.
The presence of anxiety is increased in prodromal Parkinson’s disease, but the prospective risk for Parkinson’s disease in those aged 50 years or older with new-onset anxiety was largely unknown.
Investigators analyzed data from a large UK primary care dataset that includes all people aged between 50 and 99 years who were registered with a participating practice from Jan. 1, 2008, to Dec. 31, 2018.
They identified 109,435 people (35% men) with more than one anxiety record in the database but no previous record of anxiety for 1 year or more and 878,256 people (37% men) with no history of anxiety (control group).
Features of Parkinson’s disease such as sleep problems, depression, tremor, and impaired balance were then tracked from the point of the anxiety diagnosis until 1 year before the Parkinson’s disease diagnosis.
Among those with anxiety, 331 developed Parkinson’s disease during the follow-up period, with a median time to diagnosis of 4.9 years after the first recorded episode of anxiety.
The incidence of Parkinson’s disease was 1.2 per 1000 person-years (95% CI, 0.92-1.13) in those with anxiety versus 0.49 (95% CI, 0.47-0.52) in those without anxiety.
After adjustment for age, sex, social deprivation, lifestyle factors, severe mental illness, head trauma, and dementia, the risk for Parkinson’s disease was double in those with anxiety, compared with the non-anxiety group (hazard ratio, 2.1; 95% CI, 1.9-2.4).
Individuals without anxiety also developed Parkinson’s disease later than those with anxiety.
The researchers identified specific symptoms that were associated with later development of Parkinson’s disease in those with anxiety, including depression, sleep disturbance, fatigue, and cognitive impairment, among other symptoms.
“The results suggest that there is a strong association between anxiety and diagnosis of Parkinson’s disease in patients aged over 50 years who present with a new diagnosis of anxiety,” the authors wrote. “This provides evidence for anxiety as a prodromal presentation of Parkinson’s disease.”
Future research “should explore anxiety in relation to other prodromal symptoms and how this symptom complex is associated with the incidence of Parkinson’s disease,” the researchers wrote. Doing so “may lead to earlier diagnosis and better management of Parkinson’s disease.”
This study was funded by the European Union. Specific authors received funding from the National Institute for Health and Care Research and the Alzheimer’s Society Clinical Training Fellowship program. The authors declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE BRITISH JOURNAL OF GENERAL PRACTICE