Parkinson's Disease

The hallmark of Parkinson’s disease is the accompanying motor symptoms, but the condition can bring other challenges. Among those are nonmotor symptoms, including depression, dementia, and even psychosis.

The culprit is Lewy bodies, which are also responsible for Lewy body dementia. “What we call Lewy body dementia and Parkinson’s disease are caused by the same pathological process – the formation of Lewy bodies in the brain,” Leslie Citrome, MD, MPH, said in an interview. Dr. Citrome discussed some of the psychiatric comorbidities associated with Parkinson’s disease at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

In fact, the association goes both ways. “Many people with Parkinson’s disease develop a dementia. Many people with Lewy body dementia develop motor symptoms that look just like Parkinson’s disease,” said Dr. Citrome, professor of psychiatry and behavioral sciences at New York Medical College, Valhalla, and president of the American Society for Clinical Psychopharmacology.

The motor symptoms of Parkinson’s disease are generally attributable to loss of striatal dopaminergic neurons, while nonmotor symptoms can be traced to loss of neurons in nondopaminergic regions. Nonmotor symptoms – often including sleep disorders, depression, cognitive changes, and psychosis – may occur before motor symptoms. Other problems may include autonomic dysfunction, such as constipation, sexual dysfunction, sweating, or urinary retention.

Patients might not be aware that nonmotor symptoms can occur with Parkinson’s disease and may not even consider mentioning mood changes or hallucinations to their neurologist. Family members may also be unaware.

Sleep problems are common in Parkinson’s disease, including rapid eye-movement sleep behavior disorders, vivid dreams, restless legs syndrome, insomnia, and daytime somnolence. Dopamine agonists may also cause unintended sleep.

Depression is extremely common, affecting up to 90% of Parkinson’s disease patients, and this may be related to dopaminergic losses. Antidepressant medications can worsen Parkinson’s disease symptoms: Tricyclic antidepressants increase risk of adverse events from anticholinergic drugs. Selective serotonin reuptake inhibitors (SSRIs) can exacerbate tremor and may increase risk of serotonin syndrome when combined with MAO‐B inhibitors.

Dr. Citrome was not aware of any antidepressant drugs that have been tested specifically in Parkinson’s disease patients, though “I’d be surprised if there wasn’t,” he said during the Q&A session. “There’s no one perfect antidepressant for people with depression associated with Parkinson’s disease. I would make sure to select one that they would tolerate and be willing to take and that doesn’t interfere with their treatment of their movement disorder, and (I would make sure) that there’s no drug-drug interaction,” he said.

Cognitive impairment or dementia is also very common, affecting about 75% of Parkinson’s patients. This can include reduced working memory, learning, and planning, and generally does not manifest until at least 1 year after motor symptoms have begun. Rivastigmine is Food and Drug Administration–approved for treatment of cognitive impairment in Parkinson’s disease.

As many as 60% of Parkinson’s disease patients suffer from psychosis at some point, often visual hallucinations or delusions, which can include beliefs of spousal infidelity.

Many clinicians prescribe quetiapine off label, but there are not compelling data to support that it reduces intensity and frequency of hallucinations and delusions, according to Dr. Citrome. However, it is relatively easy to prescribe, requiring no preauthorizations, it is inexpensive, and it may improve sleep.

The FDA approved pimavanserin in 2016 for hallucinations and delusions in Parkinson’s disease, and it doesn’t worsen motor symptoms, Dr. Citrome said. That’s because pimavanserin is a highly selective antagonist of the 5-HT2A receptor, with no effect on dopaminergic, histaminergic, adrenergic, or muscarinic receptors.

The drug improves positive symptoms beginning at days 29 and 43, compared with placebo. An analysis by Dr. Citrome’s group found a number needed to treat (NNT) of 7 to gain a benefit over placebo if the metric is a ≥ 30% reduction in baseline symptom score. The drug had an NNT of 9 to achieve a ≥ 50% reduction, and an NNT of 5 to achieve a score of much improved or very much improved on the Clinical Global Impression–Improvement (CGI-I) scale. In general, an NNT less than 10 suggests that a drug is clinically useful.

In contrast, the number needed to harm (NNH) represents the number of patients who would need to receive a therapy to add one adverse event, compared with placebo. A number greater than 10 indicates that the therapy may be tolerable.

Using various measures, the NNH was well over 10 for pimavanserin. With respect to somnolence, the NNH over placebo was 138, and for a weight gain of 7% or more, the NNH was 594.

Overall, the study found that 4 patients would need to be treated to achieve a benefit over placebo with respect to a ≥ 3–point improvement in the Scale of Positive Symptoms–Parkinson’s Disease (SAPS-PD), while 21 would need to receive the drug to lead to one additional discontinuation because of an adverse event, compared to placebo.

When researchers compared pimavanserin to off-label use of quetiapine, olanzapine, and clozapine, they found a Cohen’s d value of 0.50, which was better than quetiapine and olanzapine, but lower than for clozapine. However, there is no requirement of blood monitoring, and clozapine can potentially worsen motor symptoms.

Dr. Citrome’s presentation should be a reminder to neurologists that psychiatric disorders are an important patient concern, said Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, who moderated the session.

“I think this serves as a model to recognize that many neurological disorders actually present with numerous psychiatric disorders,” Dr. Nasrallah said during the meeting, presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Dr. Citrome has consulted for AbbVie, Acadia, Alkermes, Allergan, Angelini, Astellas, Avanir, Axsome, BioXcel, Boehringer-Ingelheim, Cadent Therapeutics, Eisai, Impel, Intra-Cellular, Janssen, Karuna, Lundbeck, Lyndra, MedAvante-ProPhase, Merck, Neurocrine, Noven, Otsuka, Ovid, Relmada, Sage, Sunovion, and Teva. He has been a speaker for most of those companies, and he holds stock in Bristol Myers Squibb, Eli Lilly, J&J, Merck, and Pfizer.

Dr. Nasrallah has consulted for Acadia, Alkermes, Allergan, Boehringer-Ingelheim, Indivior, Intra-Cellular, Janssen, Neurocrine, Otsuka, Sunovion, and Teva. He has served on a speakers bureau for most of those companies, in addition to that of Noven.

The hallmark of Parkinson’s disease is the accompanying motor symptoms, but the condition can bring other challenges. Among those are nonmotor symptoms, including depression, dementia, and even psychosis.

The culprit is Lewy bodies, which are also responsible for Lewy body dementia. “What we call Lewy body dementia and Parkinson’s disease are caused by the same pathological process – the formation of Lewy bodies in the brain,” Leslie Citrome, MD, MPH, said in an interview. Dr. Citrome discussed some of the psychiatric comorbidities associated with Parkinson’s disease at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

In fact, the association goes both ways. “Many people with Parkinson’s disease develop a dementia. Many people with Lewy body dementia develop motor symptoms that look just like Parkinson’s disease,” said Dr. Citrome, professor of psychiatry and behavioral sciences at New York Medical College, Valhalla, and president of the American Society for Clinical Psychopharmacology.

The motor symptoms of Parkinson’s disease are generally attributable to loss of striatal dopaminergic neurons, while nonmotor symptoms can be traced to loss of neurons in nondopaminergic regions. Nonmotor symptoms – often including sleep disorders, depression, cognitive changes, and psychosis – may occur before motor symptoms. Other problems may include autonomic dysfunction, such as constipation, sexual dysfunction, sweating, or urinary retention.

Patients might not be aware that nonmotor symptoms can occur with Parkinson’s disease and may not even consider mentioning mood changes or hallucinations to their neurologist. Family members may also be unaware.

Sleep problems are common in Parkinson’s disease, including rapid eye-movement sleep behavior disorders, vivid dreams, restless legs syndrome, insomnia, and daytime somnolence. Dopamine agonists may also cause unintended sleep.

Depression is extremely common, affecting up to 90% of Parkinson’s disease patients, and this may be related to dopaminergic losses. Antidepressant medications can worsen Parkinson’s disease symptoms: Tricyclic antidepressants increase risk of adverse events from anticholinergic drugs. Selective serotonin reuptake inhibitors (SSRIs) can exacerbate tremor and may increase risk of serotonin syndrome when combined with MAO‐B inhibitors.

Dr. Citrome was not aware of any antidepressant drugs that have been tested specifically in Parkinson’s disease patients, though “I’d be surprised if there wasn’t,” he said during the Q&A session. “There’s no one perfect antidepressant for people with depression associated with Parkinson’s disease. I would make sure to select one that they would tolerate and be willing to take and that doesn’t interfere with their treatment of their movement disorder, and (I would make sure) that there’s no drug-drug interaction,” he said.

Cognitive impairment or dementia is also very common, affecting about 75% of Parkinson’s patients. This can include reduced working memory, learning, and planning, and generally does not manifest until at least 1 year after motor symptoms have begun. Rivastigmine is Food and Drug Administration–approved for treatment of cognitive impairment in Parkinson’s disease.

As many as 60% of Parkinson’s disease patients suffer from psychosis at some point, often visual hallucinations or delusions, which can include beliefs of spousal infidelity.

Many clinicians prescribe quetiapine off label, but there are not compelling data to support that it reduces intensity and frequency of hallucinations and delusions, according to Dr. Citrome. However, it is relatively easy to prescribe, requiring no preauthorizations, it is inexpensive, and it may improve sleep.

The FDA approved pimavanserin in 2016 for hallucinations and delusions in Parkinson’s disease, and it doesn’t worsen motor symptoms, Dr. Citrome said. That’s because pimavanserin is a highly selective antagonist of the 5-HT2A receptor, with no effect on dopaminergic, histaminergic, adrenergic, or muscarinic receptors.

The drug improves positive symptoms beginning at days 29 and 43, compared with placebo. An analysis by Dr. Citrome’s group found a number needed to treat (NNT) of 7 to gain a benefit over placebo if the metric is a ≥ 30% reduction in baseline symptom score. The drug had an NNT of 9 to achieve a ≥ 50% reduction, and an NNT of 5 to achieve a score of much improved or very much improved on the Clinical Global Impression–Improvement (CGI-I) scale. In general, an NNT less than 10 suggests that a drug is clinically useful.

In contrast, the number needed to harm (NNH) represents the number of patients who would need to receive a therapy to add one adverse event, compared with placebo. A number greater than 10 indicates that the therapy may be tolerable.

Using various measures, the NNH was well over 10 for pimavanserin. With respect to somnolence, the NNH over placebo was 138, and for a weight gain of 7% or more, the NNH was 594.

Overall, the study found that 4 patients would need to be treated to achieve a benefit over placebo with respect to a ≥ 3–point improvement in the Scale of Positive Symptoms–Parkinson’s Disease (SAPS-PD), while 21 would need to receive the drug to lead to one additional discontinuation because of an adverse event, compared to placebo.

When researchers compared pimavanserin to off-label use of quetiapine, olanzapine, and clozapine, they found a Cohen’s d value of 0.50, which was better than quetiapine and olanzapine, but lower than for clozapine. However, there is no requirement of blood monitoring, and clozapine can potentially worsen motor symptoms.

Dr. Citrome’s presentation should be a reminder to neurologists that psychiatric disorders are an important patient concern, said Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, who moderated the session.

“I think this serves as a model to recognize that many neurological disorders actually present with numerous psychiatric disorders,” Dr. Nasrallah said during the meeting, presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Dr. Citrome has consulted for AbbVie, Acadia, Alkermes, Allergan, Angelini, Astellas, Avanir, Axsome, BioXcel, Boehringer-Ingelheim, Cadent Therapeutics, Eisai, Impel, Intra-Cellular, Janssen, Karuna, Lundbeck, Lyndra, MedAvante-ProPhase, Merck, Neurocrine, Noven, Otsuka, Ovid, Relmada, Sage, Sunovion, and Teva. He has been a speaker for most of those companies, and he holds stock in Bristol Myers Squibb, Eli Lilly, J&J, Merck, and Pfizer.

Dr. Nasrallah has consulted for Acadia, Alkermes, Allergan, Boehringer-Ingelheim, Indivior, Intra-Cellular, Janssen, Neurocrine, Otsuka, Sunovion, and Teva. He has served on a speakers bureau for most of those companies, in addition to that of Noven.

The hallmark of Parkinson’s disease is the accompanying motor symptoms, but the condition can bring other challenges. Among those are nonmotor symptoms, including depression, dementia, and even psychosis.

The culprit is Lewy bodies, which are also responsible for Lewy body dementia. “What we call Lewy body dementia and Parkinson’s disease are caused by the same pathological process – the formation of Lewy bodies in the brain,” Leslie Citrome, MD, MPH, said in an interview. Dr. Citrome discussed some of the psychiatric comorbidities associated with Parkinson’s disease at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

In fact, the association goes both ways. “Many people with Parkinson’s disease develop a dementia. Many people with Lewy body dementia develop motor symptoms that look just like Parkinson’s disease,” said Dr. Citrome, professor of psychiatry and behavioral sciences at New York Medical College, Valhalla, and president of the American Society for Clinical Psychopharmacology.

The motor symptoms of Parkinson’s disease are generally attributable to loss of striatal dopaminergic neurons, while nonmotor symptoms can be traced to loss of neurons in nondopaminergic regions. Nonmotor symptoms – often including sleep disorders, depression, cognitive changes, and psychosis – may occur before motor symptoms. Other problems may include autonomic dysfunction, such as constipation, sexual dysfunction, sweating, or urinary retention.

Patients might not be aware that nonmotor symptoms can occur with Parkinson’s disease and may not even consider mentioning mood changes or hallucinations to their neurologist. Family members may also be unaware.

Sleep problems are common in Parkinson’s disease, including rapid eye-movement sleep behavior disorders, vivid dreams, restless legs syndrome, insomnia, and daytime somnolence. Dopamine agonists may also cause unintended sleep.

Depression is extremely common, affecting up to 90% of Parkinson’s disease patients, and this may be related to dopaminergic losses. Antidepressant medications can worsen Parkinson’s disease symptoms: Tricyclic antidepressants increase risk of adverse events from anticholinergic drugs. Selective serotonin reuptake inhibitors (SSRIs) can exacerbate tremor and may increase risk of serotonin syndrome when combined with MAO‐B inhibitors.

Dr. Citrome was not aware of any antidepressant drugs that have been tested specifically in Parkinson’s disease patients, though “I’d be surprised if there wasn’t,” he said during the Q&A session. “There’s no one perfect antidepressant for people with depression associated with Parkinson’s disease. I would make sure to select one that they would tolerate and be willing to take and that doesn’t interfere with their treatment of their movement disorder, and (I would make sure) that there’s no drug-drug interaction,” he said.

Cognitive impairment or dementia is also very common, affecting about 75% of Parkinson’s patients. This can include reduced working memory, learning, and planning, and generally does not manifest until at least 1 year after motor symptoms have begun. Rivastigmine is Food and Drug Administration–approved for treatment of cognitive impairment in Parkinson’s disease.

As many as 60% of Parkinson’s disease patients suffer from psychosis at some point, often visual hallucinations or delusions, which can include beliefs of spousal infidelity.

Many clinicians prescribe quetiapine off label, but there are not compelling data to support that it reduces intensity and frequency of hallucinations and delusions, according to Dr. Citrome. However, it is relatively easy to prescribe, requiring no preauthorizations, it is inexpensive, and it may improve sleep.

The FDA approved pimavanserin in 2016 for hallucinations and delusions in Parkinson’s disease, and it doesn’t worsen motor symptoms, Dr. Citrome said. That’s because pimavanserin is a highly selective antagonist of the 5-HT2A receptor, with no effect on dopaminergic, histaminergic, adrenergic, or muscarinic receptors.

The drug improves positive symptoms beginning at days 29 and 43, compared with placebo. An analysis by Dr. Citrome’s group found a number needed to treat (NNT) of 7 to gain a benefit over placebo if the metric is a ≥ 30% reduction in baseline symptom score. The drug had an NNT of 9 to achieve a ≥ 50% reduction, and an NNT of 5 to achieve a score of much improved or very much improved on the Clinical Global Impression–Improvement (CGI-I) scale. In general, an NNT less than 10 suggests that a drug is clinically useful.

In contrast, the number needed to harm (NNH) represents the number of patients who would need to receive a therapy to add one adverse event, compared with placebo. A number greater than 10 indicates that the therapy may be tolerable.

Using various measures, the NNH was well over 10 for pimavanserin. With respect to somnolence, the NNH over placebo was 138, and for a weight gain of 7% or more, the NNH was 594.

Overall, the study found that 4 patients would need to be treated to achieve a benefit over placebo with respect to a ≥ 3–point improvement in the Scale of Positive Symptoms–Parkinson’s Disease (SAPS-PD), while 21 would need to receive the drug to lead to one additional discontinuation because of an adverse event, compared to placebo.

When researchers compared pimavanserin to off-label use of quetiapine, olanzapine, and clozapine, they found a Cohen’s d value of 0.50, which was better than quetiapine and olanzapine, but lower than for clozapine. However, there is no requirement of blood monitoring, and clozapine can potentially worsen motor symptoms.

Dr. Citrome’s presentation should be a reminder to neurologists that psychiatric disorders are an important patient concern, said Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, who moderated the session.

“I think this serves as a model to recognize that many neurological disorders actually present with numerous psychiatric disorders,” Dr. Nasrallah said during the meeting, presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Dr. Citrome has consulted for AbbVie, Acadia, Alkermes, Allergan, Angelini, Astellas, Avanir, Axsome, BioXcel, Boehringer-Ingelheim, Cadent Therapeutics, Eisai, Impel, Intra-Cellular, Janssen, Karuna, Lundbeck, Lyndra, MedAvante-ProPhase, Merck, Neurocrine, Noven, Otsuka, Ovid, Relmada, Sage, Sunovion, and Teva. He has been a speaker for most of those companies, and he holds stock in Bristol Myers Squibb, Eli Lilly, J&J, Merck, and Pfizer.

Dr. Nasrallah has consulted for Acadia, Alkermes, Allergan, Boehringer-Ingelheim, Indivior, Intra-Cellular, Janssen, Neurocrine, Otsuka, Sunovion, and Teva. He has served on a speakers bureau for most of those companies, in addition to that of Noven.

Parkinson’s disease patients who develop anxiety early in their disease are at risk for reduced physical activity, which promotes further anxiety and cognitive decline, data from nearly 500 individuals show.

Anxiety occurs in 20%-60% of Parkinson’s disease (PD) patients but often goes undiagnosed, wrote Jacob D. Jones, PhD, of California State University, San Bernardino, and colleagues.

“Anxiety can attenuate motivation to engage in physical activity leading to more anxiety and other negative cognitive outcomes,” although physical activity has been shown to improve cognitive function in PD patients, they said. However, physical activity as a mediator between anxiety and cognitive function in PD has not been well studied, they noted.

In a study published in Mental Health and Physical Activity the researchers identified 487 adults with newly diagnosed PD within the past 2 years who were enrolled in the Parkinson’s Progression Markers Initiative. Participants were followed for up to 5 years and completed neuropsychological tests, tests of motor severity, and self-reports on anxiety and physical activity. Anxiety was assessed using the State-Trait Anxiety Inventory-Trait (STAI-T) subscale. Physical activity was assessed using the Physical Activity Scale for the Elderly (PASE). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale-Part III (UPDRS). The average age of the participants was 61 years, 65% were men, and 96% were White.

Using a direct-effect model, the researchers found that individuals whose anxiety increased during the study period also showed signs of cognitive decline. A significant between-person effect showed that individuals who were generally more anxious also scored lower on cognitive tests over the 5-year study period.

In a mediation model computed with structural equation modeling, physical activity mediated the link between anxiety and cognition, most notably household activity.

“There was a significant within-person association between anxiety and household activities, meaning that individuals who became more anxious over the 5-year study also became less active in the home,” reported Dr. Jones and colleagues.

However, no significant indirect effect was noted regarding the between-person findings of the impact of physical activity on anxiety and cognitive decline. Although more severe anxiety was associated with less activity, cognitive performance was not associated with either type of physical activity.

The presence of a within-person effect “suggests that reductions in physical activity, specifically within the first 5 years of disease onset, may be detrimental to mental health,” the researchers emphasized. Given that the study population was newly diagnosed with PD “it is likely the within-person terms are more sensitive to changes in anxiety, physical activity, and cognition that are more directly the result of the PD process, as opposed to lifestyle/preexisting traits,” they said.

The study findings were limited by several factors, including the use of self-reports to measure physical activity, and the lack of granular information about the details of physical activity, the researchers noted. Another limitation was the inclusion of only newly diagnosed PD patients, which might limit generalizability.

“Future research is warranted to understand if other modes, intensities, or complexities of physical activity impact individuals with PD in a different manner in relation to cognition,” they said.

Dr. Jones and colleagues had no disclosures. The PPMI is supported by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including numerous pharmaceutical companies.

Parkinson’s disease patients who develop anxiety early in their disease are at risk for reduced physical activity, which promotes further anxiety and cognitive decline, data from nearly 500 individuals show.

Anxiety occurs in 20%-60% of Parkinson’s disease (PD) patients but often goes undiagnosed, wrote Jacob D. Jones, PhD, of California State University, San Bernardino, and colleagues.

“Anxiety can attenuate motivation to engage in physical activity leading to more anxiety and other negative cognitive outcomes,” although physical activity has been shown to improve cognitive function in PD patients, they said. However, physical activity as a mediator between anxiety and cognitive function in PD has not been well studied, they noted.

In a study published in Mental Health and Physical Activity the researchers identified 487 adults with newly diagnosed PD within the past 2 years who were enrolled in the Parkinson’s Progression Markers Initiative. Participants were followed for up to 5 years and completed neuropsychological tests, tests of motor severity, and self-reports on anxiety and physical activity. Anxiety was assessed using the State-Trait Anxiety Inventory-Trait (STAI-T) subscale. Physical activity was assessed using the Physical Activity Scale for the Elderly (PASE). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale-Part III (UPDRS). The average age of the participants was 61 years, 65% were men, and 96% were White.

Using a direct-effect model, the researchers found that individuals whose anxiety increased during the study period also showed signs of cognitive decline. A significant between-person effect showed that individuals who were generally more anxious also scored lower on cognitive tests over the 5-year study period.

In a mediation model computed with structural equation modeling, physical activity mediated the link between anxiety and cognition, most notably household activity.

“There was a significant within-person association between anxiety and household activities, meaning that individuals who became more anxious over the 5-year study also became less active in the home,” reported Dr. Jones and colleagues.

However, no significant indirect effect was noted regarding the between-person findings of the impact of physical activity on anxiety and cognitive decline. Although more severe anxiety was associated with less activity, cognitive performance was not associated with either type of physical activity.

The presence of a within-person effect “suggests that reductions in physical activity, specifically within the first 5 years of disease onset, may be detrimental to mental health,” the researchers emphasized. Given that the study population was newly diagnosed with PD “it is likely the within-person terms are more sensitive to changes in anxiety, physical activity, and cognition that are more directly the result of the PD process, as opposed to lifestyle/preexisting traits,” they said.

The study findings were limited by several factors, including the use of self-reports to measure physical activity, and the lack of granular information about the details of physical activity, the researchers noted. Another limitation was the inclusion of only newly diagnosed PD patients, which might limit generalizability.

“Future research is warranted to understand if other modes, intensities, or complexities of physical activity impact individuals with PD in a different manner in relation to cognition,” they said.

Dr. Jones and colleagues had no disclosures. The PPMI is supported by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including numerous pharmaceutical companies.

Parkinson’s disease patients who develop anxiety early in their disease are at risk for reduced physical activity, which promotes further anxiety and cognitive decline, data from nearly 500 individuals show.

Anxiety occurs in 20%-60% of Parkinson’s disease (PD) patients but often goes undiagnosed, wrote Jacob D. Jones, PhD, of California State University, San Bernardino, and colleagues.

“Anxiety can attenuate motivation to engage in physical activity leading to more anxiety and other negative cognitive outcomes,” although physical activity has been shown to improve cognitive function in PD patients, they said. However, physical activity as a mediator between anxiety and cognitive function in PD has not been well studied, they noted.

In a study published in Mental Health and Physical Activity the researchers identified 487 adults with newly diagnosed PD within the past 2 years who were enrolled in the Parkinson’s Progression Markers Initiative. Participants were followed for up to 5 years and completed neuropsychological tests, tests of motor severity, and self-reports on anxiety and physical activity. Anxiety was assessed using the State-Trait Anxiety Inventory-Trait (STAI-T) subscale. Physical activity was assessed using the Physical Activity Scale for the Elderly (PASE). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale-Part III (UPDRS). The average age of the participants was 61 years, 65% were men, and 96% were White.

Using a direct-effect model, the researchers found that individuals whose anxiety increased during the study period also showed signs of cognitive decline. A significant between-person effect showed that individuals who were generally more anxious also scored lower on cognitive tests over the 5-year study period.

In a mediation model computed with structural equation modeling, physical activity mediated the link between anxiety and cognition, most notably household activity.

“There was a significant within-person association between anxiety and household activities, meaning that individuals who became more anxious over the 5-year study also became less active in the home,” reported Dr. Jones and colleagues.

However, no significant indirect effect was noted regarding the between-person findings of the impact of physical activity on anxiety and cognitive decline. Although more severe anxiety was associated with less activity, cognitive performance was not associated with either type of physical activity.

The presence of a within-person effect “suggests that reductions in physical activity, specifically within the first 5 years of disease onset, may be detrimental to mental health,” the researchers emphasized. Given that the study population was newly diagnosed with PD “it is likely the within-person terms are more sensitive to changes in anxiety, physical activity, and cognition that are more directly the result of the PD process, as opposed to lifestyle/preexisting traits,” they said.

The study findings were limited by several factors, including the use of self-reports to measure physical activity, and the lack of granular information about the details of physical activity, the researchers noted. Another limitation was the inclusion of only newly diagnosed PD patients, which might limit generalizability.

“Future research is warranted to understand if other modes, intensities, or complexities of physical activity impact individuals with PD in a different manner in relation to cognition,” they said.

Dr. Jones and colleagues had no disclosures. The PPMI is supported by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including numerous pharmaceutical companies.

Adults aged 65 years and older who develop psychotic manifestations are significantly more likely than those without such manifestations to develop prodromal Parkinson’s disease, data from 925 individuals suggest.

“The presence of perceptual abnormalities and/or delusional ideation among community-dwelling elderly individuals is more widespread than considered in the past,” wrote Ioanna Pachi, MD, of National and Kapodistrian University of Athens Medical School and colleagues. However, those psychoses and their potential impact on prodromal Parkinson’s disease (PD) have not been well studied in community-dwelling populations, they noted in the study, published in Parkinsonism and Related Disorders.

In the study, Dr. Pachi and colleagues reviewed data from 914 participants in the Hellenic Longitudinal Investigation of Aging and Diet study (HELIAD), a cross-sectional, population-based cohort study of older adults in Greece. The average age of the participants was 76 years, and 41% were men. Participants had no delusional features at baseline; delusional features were assessed using the Neuropsychiatric Inventory scale and the Columbia University Scale for Psychopathology in Alzheimer’s disease. The researchers calculated the probability of prodromal PD (pPD) for each participant based on the 2019 International Parkinson and Movement Disorders Society research criteria for prodromal PD.

Over a 3-year follow-up period, 20 participants developed psychotic manifestations and were 1.3 times more likely to have pPD, compared with those without psychoses (P = .006). Those with new-onset psychotic features were categorized together as the NPSY group, regardless of symptom severity or frequency; those with no symptoms at either baseline or during follow-up were categorized as unaffected (UPSY). Most of the NPSY participants showed isolated delusional features, although some expressed hallucinations. Most symptoms were mild.

New-onset psychosis was associated with a fivefold increased risk of both subthreshold parkinsonism and depression (adjusted odds ratios, 4.5 and 5.0, respectively) and with a threefold increased risk of constipation (aOR 2.6). Other factors, including nonsmoking, global cognitive deficit, and anxiety were not significantly associated with new-onset psychotic symptoms after adjusting for confounding factors.

Although the mechanism behind the association remains unclear, “the parallel evolution of psychotic features and prodromal PD could be related to the spreading pattern of neuronal damage that occurs in PD,” the researchers wrote.

The study findings were limited by several factors, including the administration of neuropsychiatric questionnaires by nonpsychiatrists, and lack of detailed psychiatric history, including complete information on medication use, the researchers noted. The small size of the NPSY group also prevented evaluation of the potential associations between pPD and different modalities of hallucinations, they said.

However, the results were strengthened by the overall large and population-based sample size, and the comprehensive evaluation of psychotic features, they wrote. More follow-up evaluations in the HELIAD cohort are planned to further explore the underlying mechanism of the association between late-life psychosis and pPD.

“Provided that these results are confirmed in other community cohorts of elderly subjects, psychotic features may be added to the list of manifestations of pPD,” they concluded.

The study was supported in part by grants from the Alzheimer’s Association, ARISTEIA, and the ESPA-EU program Excellence Grant. It was cofunded by the European Social Fund and Greek National resources, the Ministry for Health and Social Solidarity, Greece, and the Greek State Scholarships Foundation. Dr. Pachi had no disclosures.

Adults aged 65 years and older who develop psychotic manifestations are significantly more likely than those without such manifestations to develop prodromal Parkinson’s disease, data from 925 individuals suggest.

“The presence of perceptual abnormalities and/or delusional ideation among community-dwelling elderly individuals is more widespread than considered in the past,” wrote Ioanna Pachi, MD, of National and Kapodistrian University of Athens Medical School and colleagues. However, those psychoses and their potential impact on prodromal Parkinson’s disease (PD) have not been well studied in community-dwelling populations, they noted in the study, published in Parkinsonism and Related Disorders.

In the study, Dr. Pachi and colleagues reviewed data from 914 participants in the Hellenic Longitudinal Investigation of Aging and Diet study (HELIAD), a cross-sectional, population-based cohort study of older adults in Greece. The average age of the participants was 76 years, and 41% were men. Participants had no delusional features at baseline; delusional features were assessed using the Neuropsychiatric Inventory scale and the Columbia University Scale for Psychopathology in Alzheimer’s disease. The researchers calculated the probability of prodromal PD (pPD) for each participant based on the 2019 International Parkinson and Movement Disorders Society research criteria for prodromal PD.

Over a 3-year follow-up period, 20 participants developed psychotic manifestations and were 1.3 times more likely to have pPD, compared with those without psychoses (P = .006). Those with new-onset psychotic features were categorized together as the NPSY group, regardless of symptom severity or frequency; those with no symptoms at either baseline or during follow-up were categorized as unaffected (UPSY). Most of the NPSY participants showed isolated delusional features, although some expressed hallucinations. Most symptoms were mild.

New-onset psychosis was associated with a fivefold increased risk of both subthreshold parkinsonism and depression (adjusted odds ratios, 4.5 and 5.0, respectively) and with a threefold increased risk of constipation (aOR 2.6). Other factors, including nonsmoking, global cognitive deficit, and anxiety were not significantly associated with new-onset psychotic symptoms after adjusting for confounding factors.

Although the mechanism behind the association remains unclear, “the parallel evolution of psychotic features and prodromal PD could be related to the spreading pattern of neuronal damage that occurs in PD,” the researchers wrote.

The study findings were limited by several factors, including the administration of neuropsychiatric questionnaires by nonpsychiatrists, and lack of detailed psychiatric history, including complete information on medication use, the researchers noted. The small size of the NPSY group also prevented evaluation of the potential associations between pPD and different modalities of hallucinations, they said.

However, the results were strengthened by the overall large and population-based sample size, and the comprehensive evaluation of psychotic features, they wrote. More follow-up evaluations in the HELIAD cohort are planned to further explore the underlying mechanism of the association between late-life psychosis and pPD.

“Provided that these results are confirmed in other community cohorts of elderly subjects, psychotic features may be added to the list of manifestations of pPD,” they concluded.

The study was supported in part by grants from the Alzheimer’s Association, ARISTEIA, and the ESPA-EU program Excellence Grant. It was cofunded by the European Social Fund and Greek National resources, the Ministry for Health and Social Solidarity, Greece, and the Greek State Scholarships Foundation. Dr. Pachi had no disclosures.

Adults aged 65 years and older who develop psychotic manifestations are significantly more likely than those without such manifestations to develop prodromal Parkinson’s disease, data from 925 individuals suggest.

“The presence of perceptual abnormalities and/or delusional ideation among community-dwelling elderly individuals is more widespread than considered in the past,” wrote Ioanna Pachi, MD, of National and Kapodistrian University of Athens Medical School and colleagues. However, those psychoses and their potential impact on prodromal Parkinson’s disease (PD) have not been well studied in community-dwelling populations, they noted in the study, published in Parkinsonism and Related Disorders.

In the study, Dr. Pachi and colleagues reviewed data from 914 participants in the Hellenic Longitudinal Investigation of Aging and Diet study (HELIAD), a cross-sectional, population-based cohort study of older adults in Greece. The average age of the participants was 76 years, and 41% were men. Participants had no delusional features at baseline; delusional features were assessed using the Neuropsychiatric Inventory scale and the Columbia University Scale for Psychopathology in Alzheimer’s disease. The researchers calculated the probability of prodromal PD (pPD) for each participant based on the 2019 International Parkinson and Movement Disorders Society research criteria for prodromal PD.

Over a 3-year follow-up period, 20 participants developed psychotic manifestations and were 1.3 times more likely to have pPD, compared with those without psychoses (P = .006). Those with new-onset psychotic features were categorized together as the NPSY group, regardless of symptom severity or frequency; those with no symptoms at either baseline or during follow-up were categorized as unaffected (UPSY). Most of the NPSY participants showed isolated delusional features, although some expressed hallucinations. Most symptoms were mild.

New-onset psychosis was associated with a fivefold increased risk of both subthreshold parkinsonism and depression (adjusted odds ratios, 4.5 and 5.0, respectively) and with a threefold increased risk of constipation (aOR 2.6). Other factors, including nonsmoking, global cognitive deficit, and anxiety were not significantly associated with new-onset psychotic symptoms after adjusting for confounding factors.

Although the mechanism behind the association remains unclear, “the parallel evolution of psychotic features and prodromal PD could be related to the spreading pattern of neuronal damage that occurs in PD,” the researchers wrote.

The study findings were limited by several factors, including the administration of neuropsychiatric questionnaires by nonpsychiatrists, and lack of detailed psychiatric history, including complete information on medication use, the researchers noted. The small size of the NPSY group also prevented evaluation of the potential associations between pPD and different modalities of hallucinations, they said.

However, the results were strengthened by the overall large and population-based sample size, and the comprehensive evaluation of psychotic features, they wrote. More follow-up evaluations in the HELIAD cohort are planned to further explore the underlying mechanism of the association between late-life psychosis and pPD.

“Provided that these results are confirmed in other community cohorts of elderly subjects, psychotic features may be added to the list of manifestations of pPD,” they concluded.

The study was supported in part by grants from the Alzheimer’s Association, ARISTEIA, and the ESPA-EU program Excellence Grant. It was cofunded by the European Social Fund and Greek National resources, the Ministry for Health and Social Solidarity, Greece, and the Greek State Scholarships Foundation. Dr. Pachi had no disclosures.

Pimavanserin, a novel antipsychotic drug used to manage hallucinations and delusions in Parkinson’s disease, may lead to increased hospitalizations and deaths, according to a new study.

A retrospective cohort study of elderly patients with Parkinson’s disease who were in long-term care facilities found that the use of pimavanserin (Nuplazid) was associated with an increased risk of 30-day hospitalization and mortality for up to a year.

“Given that a previous study showed typical and atypical antipsychotics more than doubled mortality risk in patients with Parkinson’s disease, we aimed to assess the risk of hospitalization and death associated with pimavanserin,” wrote lead author Y. Joseph Hwang, MD, Johns Hopkins University, Baltimore, and colleagues in the paper. “These findings, in a large real-world cohort within long-term care facilities, may help to inform decisions regarding its risk-benefit balance among patients with Parkinson’s disease.”

The findings were published online Aug. 13 in Neurology.

The researchers enrolled 2,186 patients with Parkinson’s disease aged 65 years and older in Medicare-certified long-term care facilities who also had a pimavanserin prescription and 18,212 nonusers of pimavanserin between Nov. 1, 2015, and December 31, 2018. Patients in the pimavanserin group used the drug over the course of the entire study period. Hospitalization and mortality were calculated from the date of pimavanserin prescription. Propensity score–based inverse probability of treatment weighting (IPTW) was used to balance the two groups on 24 baseline characteristics such as age, sex, and comorbidities.

Pimavanserin use was associated with a 24% higher risk of 30-day hospitalization (adjusted hazard ratio, 1.24; 95% confidence interval, 1.06-1.43). However, “the association did not reach statistical significance in a smaller subcohort of propensity score-matched users and nonusers,” Dr. Hwang and colleagues wrote.

Pimavanserin use was also linked to higher mortality at:

• 90 days (aHR, 1.20; 95% CI, 1.02-1.41).
• 180 days (aHR, 1.28; 95% CI, 1.13-1.45).
• 365 days (aHR, 1.56; 95% CI, 1.42-1.72).

No associations were found between pimavanserin use and 90-day hospitalization (aHR, 1.10; 95% CI, 0.99-1.24) nor with 30-day mortality (aHR, 0.76; 95% CI, 0.56-1.03).
 

Important considerations

“This study raises three important points to consider for any practicing neurology provider: 1) how to address and interpret risks associated with pimavanserin use in this patient population 2) utility of pimavanserin 3) interpretation of data showing increased mortality in patients being treated for Parkinson’s disease psychosis,” wrote Farwa Ali, MBBS, of the Mayo Clinic, Rochester, Minn., in an accompanying editorial published in Neurology.

Hallucinations and delusions are highly prevalent in Parkinson’s disease; as many as 60% of patients will develop psychosis over the course of their illness. Pimavanserin is a selective serotonin inverse agonist which targets 5-HT_2A serotonin receptors in the brain, decreasing their activity in order to attenuate hallucinations and delusions.

“Pimavanserin has been approved by the FDA [Food and Drug Administration] for Parkinson’s disease psychosis, but its safety has been called into question based on previous reports of increased mortality risk, compared with a rather modest benefit seen in a 6-week clinical trial, the duration of which limits determination of long-term safety,” wrote Dr. Ali.

Pimavanserin carries a boxed warning that elderly patients with dementia may be at an increased risk of death. After its approval in 2016, the U.S. FDA later reviewed 893 deaths in association with pimavanserin during the postmarketing surveillance period – “an unexpected number in a new drug,” Dr. Hwang and colleagues noted. “It [the FDA] noted that most reports occurred in a population with high underlying death rates and did not signal any additional risk beyond the current warning for all antipsychotics, which could have resulted in annual mortality rates of up to 60%.”

As the first cohort study to examine hospitalization and death between pimavanserin users and nonusers, “the study confirms previous concerns regarding safety of pimavanserin and more importantly brings to attention the importance of carefully considering risks and benefits of pharmacotherapy in Parkinson’s disease psychosis, clear communication with patients and families, and close observation to ensure safety,” wrote Dr. Ali.

The study limitations include its observational design, which subjected the findings to residual confounding.

“While we developed models to maximize the strength of causal inference, our comparison group was pimavanserin nonusers and the very reason for prescription of pimavanserin could have predisposed its users to the outcomes of hospitalization and death, introducing confounding by indication,” Dr. Hwang and colleagues wrote in the paper.

Additionally, “while robust analyses were conducted to ensure pimavanserin users and nonusers were comparable, Dr. Hwang et al. did find that pimavanserin users were more likely to concomitantly use other antipsychotic drugs which has been demonstrated as increasing the mortality risk,” Dr. Ali pointed out.

Since patients living in long-term care facilities may have a higher risk of mortality because of more severe or later-stage Parkinson’s disease, the study results “may not be generalizable to community-dwelling PD patients,” Dr. Ali wrote. “These factors are important to consider while making individual management decisions.”

Dr. Hwang and Dr. Ali disclosed no relevant financial relationships. The study authors reported no targeted funding.

Pimavanserin, a novel antipsychotic drug used to manage hallucinations and delusions in Parkinson’s disease, may lead to increased hospitalizations and deaths, according to a new study.

A retrospective cohort study of elderly patients with Parkinson’s disease who were in long-term care facilities found that the use of pimavanserin (Nuplazid) was associated with an increased risk of 30-day hospitalization and mortality for up to a year.

“Given that a previous study showed typical and atypical antipsychotics more than doubled mortality risk in patients with Parkinson’s disease, we aimed to assess the risk of hospitalization and death associated with pimavanserin,” wrote lead author Y. Joseph Hwang, MD, Johns Hopkins University, Baltimore, and colleagues in the paper. “These findings, in a large real-world cohort within long-term care facilities, may help to inform decisions regarding its risk-benefit balance among patients with Parkinson’s disease.”

The findings were published online Aug. 13 in Neurology.

The researchers enrolled 2,186 patients with Parkinson’s disease aged 65 years and older in Medicare-certified long-term care facilities who also had a pimavanserin prescription and 18,212 nonusers of pimavanserin between Nov. 1, 2015, and December 31, 2018. Patients in the pimavanserin group used the drug over the course of the entire study period. Hospitalization and mortality were calculated from the date of pimavanserin prescription. Propensity score–based inverse probability of treatment weighting (IPTW) was used to balance the two groups on 24 baseline characteristics such as age, sex, and comorbidities.

Pimavanserin use was associated with a 24% higher risk of 30-day hospitalization (adjusted hazard ratio, 1.24; 95% confidence interval, 1.06-1.43). However, “the association did not reach statistical significance in a smaller subcohort of propensity score-matched users and nonusers,” Dr. Hwang and colleagues wrote.

Pimavanserin use was also linked to higher mortality at:

• 90 days (aHR, 1.20; 95% CI, 1.02-1.41).
• 180 days (aHR, 1.28; 95% CI, 1.13-1.45).
• 365 days (aHR, 1.56; 95% CI, 1.42-1.72).

No associations were found between pimavanserin use and 90-day hospitalization (aHR, 1.10; 95% CI, 0.99-1.24) nor with 30-day mortality (aHR, 0.76; 95% CI, 0.56-1.03).
 

Important considerations

“This study raises three important points to consider for any practicing neurology provider: 1) how to address and interpret risks associated with pimavanserin use in this patient population 2) utility of pimavanserin 3) interpretation of data showing increased mortality in patients being treated for Parkinson’s disease psychosis,” wrote Farwa Ali, MBBS, of the Mayo Clinic, Rochester, Minn., in an accompanying editorial published in Neurology.

Hallucinations and delusions are highly prevalent in Parkinson’s disease; as many as 60% of patients will develop psychosis over the course of their illness. Pimavanserin is a selective serotonin inverse agonist which targets 5-HT_2A serotonin receptors in the brain, decreasing their activity in order to attenuate hallucinations and delusions.

“Pimavanserin has been approved by the FDA [Food and Drug Administration] for Parkinson’s disease psychosis, but its safety has been called into question based on previous reports of increased mortality risk, compared with a rather modest benefit seen in a 6-week clinical trial, the duration of which limits determination of long-term safety,” wrote Dr. Ali.

Pimavanserin carries a boxed warning that elderly patients with dementia may be at an increased risk of death. After its approval in 2016, the U.S. FDA later reviewed 893 deaths in association with pimavanserin during the postmarketing surveillance period – “an unexpected number in a new drug,” Dr. Hwang and colleagues noted. “It [the FDA] noted that most reports occurred in a population with high underlying death rates and did not signal any additional risk beyond the current warning for all antipsychotics, which could have resulted in annual mortality rates of up to 60%.”

As the first cohort study to examine hospitalization and death between pimavanserin users and nonusers, “the study confirms previous concerns regarding safety of pimavanserin and more importantly brings to attention the importance of carefully considering risks and benefits of pharmacotherapy in Parkinson’s disease psychosis, clear communication with patients and families, and close observation to ensure safety,” wrote Dr. Ali.

The study limitations include its observational design, which subjected the findings to residual confounding.

“While we developed models to maximize the strength of causal inference, our comparison group was pimavanserin nonusers and the very reason for prescription of pimavanserin could have predisposed its users to the outcomes of hospitalization and death, introducing confounding by indication,” Dr. Hwang and colleagues wrote in the paper.

Additionally, “while robust analyses were conducted to ensure pimavanserin users and nonusers were comparable, Dr. Hwang et al. did find that pimavanserin users were more likely to concomitantly use other antipsychotic drugs which has been demonstrated as increasing the mortality risk,” Dr. Ali pointed out.

Since patients living in long-term care facilities may have a higher risk of mortality because of more severe or later-stage Parkinson’s disease, the study results “may not be generalizable to community-dwelling PD patients,” Dr. Ali wrote. “These factors are important to consider while making individual management decisions.”

Dr. Hwang and Dr. Ali disclosed no relevant financial relationships. The study authors reported no targeted funding.

Pimavanserin, a novel antipsychotic drug used to manage hallucinations and delusions in Parkinson’s disease, may lead to increased hospitalizations and deaths, according to a new study.

A retrospective cohort study of elderly patients with Parkinson’s disease who were in long-term care facilities found that the use of pimavanserin (Nuplazid) was associated with an increased risk of 30-day hospitalization and mortality for up to a year.

“Given that a previous study showed typical and atypical antipsychotics more than doubled mortality risk in patients with Parkinson’s disease, we aimed to assess the risk of hospitalization and death associated with pimavanserin,” wrote lead author Y. Joseph Hwang, MD, Johns Hopkins University, Baltimore, and colleagues in the paper. “These findings, in a large real-world cohort within long-term care facilities, may help to inform decisions regarding its risk-benefit balance among patients with Parkinson’s disease.”

The findings were published online Aug. 13 in Neurology.

The researchers enrolled 2,186 patients with Parkinson’s disease aged 65 years and older in Medicare-certified long-term care facilities who also had a pimavanserin prescription and 18,212 nonusers of pimavanserin between Nov. 1, 2015, and December 31, 2018. Patients in the pimavanserin group used the drug over the course of the entire study period. Hospitalization and mortality were calculated from the date of pimavanserin prescription. Propensity score–based inverse probability of treatment weighting (IPTW) was used to balance the two groups on 24 baseline characteristics such as age, sex, and comorbidities.

Pimavanserin use was associated with a 24% higher risk of 30-day hospitalization (adjusted hazard ratio, 1.24; 95% confidence interval, 1.06-1.43). However, “the association did not reach statistical significance in a smaller subcohort of propensity score-matched users and nonusers,” Dr. Hwang and colleagues wrote.

Pimavanserin use was also linked to higher mortality at:

• 90 days (aHR, 1.20; 95% CI, 1.02-1.41).
• 180 days (aHR, 1.28; 95% CI, 1.13-1.45).
• 365 days (aHR, 1.56; 95% CI, 1.42-1.72).

No associations were found between pimavanserin use and 90-day hospitalization (aHR, 1.10; 95% CI, 0.99-1.24) nor with 30-day mortality (aHR, 0.76; 95% CI, 0.56-1.03).
 

Important considerations

“This study raises three important points to consider for any practicing neurology provider: 1) how to address and interpret risks associated with pimavanserin use in this patient population 2) utility of pimavanserin 3) interpretation of data showing increased mortality in patients being treated for Parkinson’s disease psychosis,” wrote Farwa Ali, MBBS, of the Mayo Clinic, Rochester, Minn., in an accompanying editorial published in Neurology.

Hallucinations and delusions are highly prevalent in Parkinson’s disease; as many as 60% of patients will develop psychosis over the course of their illness. Pimavanserin is a selective serotonin inverse agonist which targets 5-HT_2A serotonin receptors in the brain, decreasing their activity in order to attenuate hallucinations and delusions.

“Pimavanserin has been approved by the FDA [Food and Drug Administration] for Parkinson’s disease psychosis, but its safety has been called into question based on previous reports of increased mortality risk, compared with a rather modest benefit seen in a 6-week clinical trial, the duration of which limits determination of long-term safety,” wrote Dr. Ali.

Pimavanserin carries a boxed warning that elderly patients with dementia may be at an increased risk of death. After its approval in 2016, the U.S. FDA later reviewed 893 deaths in association with pimavanserin during the postmarketing surveillance period – “an unexpected number in a new drug,” Dr. Hwang and colleagues noted. “It [the FDA] noted that most reports occurred in a population with high underlying death rates and did not signal any additional risk beyond the current warning for all antipsychotics, which could have resulted in annual mortality rates of up to 60%.”

As the first cohort study to examine hospitalization and death between pimavanserin users and nonusers, “the study confirms previous concerns regarding safety of pimavanserin and more importantly brings to attention the importance of carefully considering risks and benefits of pharmacotherapy in Parkinson’s disease psychosis, clear communication with patients and families, and close observation to ensure safety,” wrote Dr. Ali.

The study limitations include its observational design, which subjected the findings to residual confounding.

“While we developed models to maximize the strength of causal inference, our comparison group was pimavanserin nonusers and the very reason for prescription of pimavanserin could have predisposed its users to the outcomes of hospitalization and death, introducing confounding by indication,” Dr. Hwang and colleagues wrote in the paper.

Additionally, “while robust analyses were conducted to ensure pimavanserin users and nonusers were comparable, Dr. Hwang et al. did find that pimavanserin users were more likely to concomitantly use other antipsychotic drugs which has been demonstrated as increasing the mortality risk,” Dr. Ali pointed out.

Since patients living in long-term care facilities may have a higher risk of mortality because of more severe or later-stage Parkinson’s disease, the study results “may not be generalizable to community-dwelling PD patients,” Dr. Ali wrote. “These factors are important to consider while making individual management decisions.”

Dr. Hwang and Dr. Ali disclosed no relevant financial relationships. The study authors reported no targeted funding.

Dancing helps slow the progression of motor and nonmotor symptoms and improves quality of life for patients with Parkinson’s disease (PD), new research shows.

Over 3 years, weekly participation in dance training classes “drastically” reduced the expected decline in motor function and significantly improved speech, tremors, balance, and stiffness, the researchers reported.

Dance training also appeared to have benefits regarding cognition, hallucinations, depression, and anxiety.

“These findings strongly suggest the benefits of dance for people with PD as a supplement to a normal treatment regimen,” the investigators noted.

Although the mechanism of benefit is unclear, dance training may help “train neural network nodes that helps either strengthen networks damaged or builds neural road maps that pass the damage,” study investigator Joseph DeSouza, PhD, principal investigator and associate professor, department of psychology, York University, Toronto, said in an interview.

The study was published online July 7, 2021, in Brain Sciences.
 

Multiple benefits

PD is a neurodegenerative disease associated with progression of motor dysfunction within the first 5 years of diagnosis. The annual rate of motor decline, as determined with the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), is between 5.2 and 8.9 points.

Prior studies that assessed various styles of dance by patients with PD showed beneficial effects regarding gait speed, balance, locomotion, and aspects of quality of life.

To investigate further, DeSouza and coauthor Karolina Bearss, a PhD candidate at York University, followed 16 patients with mild to moderate PD who participated in a weekly dance class at Canada’s National Ballet School and Trinity St. Paul’s church.

Dance for Parkinson’s Disease, which is an established dance curriculum, involves aerobic and anaerobic movements. The protocol begins with a seated warm-up, followed by barre work, and ends with moving across the floor. All participants learn choreography for an upcoming performance.

In the study, 16 patients with PD who did not participant in the dance classes served as control patients.

Over 3 years, the daily rate of motor decline, as indicated by scores on part III of the MDS-UPDRS, was zero among the dancers (slope = 0.000146), indicating no motor impairment, whereas among the nondancers, the motor decline during follow-up was as expected (P < .01), the researchers reported.

In modeling the data, the researchers determined that after completing 1,000 days of dance training, dancers will have a motor score of 19.07, compared with a score of 28.27 for nondancers.

“Our data further showed that training in dance will slow the rate of PD motor impairment progression, as measured by the UPDRS III, by close to 3 points annually in comparison to our PD subjects who did not train,” the researchers reported.

Dance training also had a beneficial effect on motor or nonmotor aspects of daily living and on motor complications, for which there was no significant decline among the PD dancers.

“For those with Parkinson’s disease, even when it’s mild, motor impairment can impact their daily functioning – how they feel about themselves. Many of these motor symptoms lead to isolation because once they get extreme, these people don’t want to go out,” Dr. DeSouza said in a news release.

“These motor symptoms lead to further psychological issues, depression, social isolation and eventually the symptoms do get worse over time. Our study shows that training with dance and music can slow this down and improve their daily living and daily function,” he added.
 

‘Great potential’

Reached for comment, Demian Kogutek, PhD, director of music therapy, University of Evansville (Indiana), said that these preliminary findings from a longitudinal study are “promising.”

“I believe that dance therapy has a great potential for PD. The longitudinal aspect of this study undoubtedly adds to the current literature. Although it is a standardized assessment, it is somewhat subjective,” Dr. Kogutek said in an interview.

Going forward, Dr. Kogutek said he’d like to see other objective outcomes measured, such as objective assessments of balance, gait, hand strength, and dexterity.

Also weighing in on the results, Karen Lee, PhD, president and CEO of Parkinson Canada, said her organization is “encouraged by these preliminary findings as exercise and healthy activities are important for people with Parkinson’s. This study is part of a growing body of research that explores the link between the impact of activities and both motor and nonmotor symptoms of Parkinson’s.

“This research adds to growing evidence about the importance of exercise as part of the management of Parkinson’s, and we encourage people living with Parkinson’s to incorporate exercise as part of their approach to managing their health,” Dr. Lee said in an interview.

Funding for the project is provided in part by a National Science and Engineering Research Council Discovery Grant and by donations from the Irpinia Club of Toronto and others. Dr. Dr. DeSouza, Ms. Bearss, Dr. Kogutek, and Dr. Lee disclosed no relevant financial relationships.

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

Dancing helps slow the progression of motor and nonmotor symptoms and improves quality of life for patients with Parkinson’s disease (PD), new research shows.

Over 3 years, weekly participation in dance training classes “drastically” reduced the expected decline in motor function and significantly improved speech, tremors, balance, and stiffness, the researchers reported.

Dance training also appeared to have benefits regarding cognition, hallucinations, depression, and anxiety.

“These findings strongly suggest the benefits of dance for people with PD as a supplement to a normal treatment regimen,” the investigators noted.

Although the mechanism of benefit is unclear, dance training may help “train neural network nodes that helps either strengthen networks damaged or builds neural road maps that pass the damage,” study investigator Joseph DeSouza, PhD, principal investigator and associate professor, department of psychology, York University, Toronto, said in an interview.

The study was published online July 7, 2021, in Brain Sciences.
 

Multiple benefits

PD is a neurodegenerative disease associated with progression of motor dysfunction within the first 5 years of diagnosis. The annual rate of motor decline, as determined with the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), is between 5.2 and 8.9 points.

Prior studies that assessed various styles of dance by patients with PD showed beneficial effects regarding gait speed, balance, locomotion, and aspects of quality of life.

To investigate further, DeSouza and coauthor Karolina Bearss, a PhD candidate at York University, followed 16 patients with mild to moderate PD who participated in a weekly dance class at Canada’s National Ballet School and Trinity St. Paul’s church.

Dance for Parkinson’s Disease, which is an established dance curriculum, involves aerobic and anaerobic movements. The protocol begins with a seated warm-up, followed by barre work, and ends with moving across the floor. All participants learn choreography for an upcoming performance.

In the study, 16 patients with PD who did not participant in the dance classes served as control patients.

Over 3 years, the daily rate of motor decline, as indicated by scores on part III of the MDS-UPDRS, was zero among the dancers (slope = 0.000146), indicating no motor impairment, whereas among the nondancers, the motor decline during follow-up was as expected (P < .01), the researchers reported.

In modeling the data, the researchers determined that after completing 1,000 days of dance training, dancers will have a motor score of 19.07, compared with a score of 28.27 for nondancers.

“Our data further showed that training in dance will slow the rate of PD motor impairment progression, as measured by the UPDRS III, by close to 3 points annually in comparison to our PD subjects who did not train,” the researchers reported.

Dance training also had a beneficial effect on motor or nonmotor aspects of daily living and on motor complications, for which there was no significant decline among the PD dancers.

“For those with Parkinson’s disease, even when it’s mild, motor impairment can impact their daily functioning – how they feel about themselves. Many of these motor symptoms lead to isolation because once they get extreme, these people don’t want to go out,” Dr. DeSouza said in a news release.

“These motor symptoms lead to further psychological issues, depression, social isolation and eventually the symptoms do get worse over time. Our study shows that training with dance and music can slow this down and improve their daily living and daily function,” he added.
 

‘Great potential’

Reached for comment, Demian Kogutek, PhD, director of music therapy, University of Evansville (Indiana), said that these preliminary findings from a longitudinal study are “promising.”

“I believe that dance therapy has a great potential for PD. The longitudinal aspect of this study undoubtedly adds to the current literature. Although it is a standardized assessment, it is somewhat subjective,” Dr. Kogutek said in an interview.

Going forward, Dr. Kogutek said he’d like to see other objective outcomes measured, such as objective assessments of balance, gait, hand strength, and dexterity.

Also weighing in on the results, Karen Lee, PhD, president and CEO of Parkinson Canada, said her organization is “encouraged by these preliminary findings as exercise and healthy activities are important for people with Parkinson’s. This study is part of a growing body of research that explores the link between the impact of activities and both motor and nonmotor symptoms of Parkinson’s.

“This research adds to growing evidence about the importance of exercise as part of the management of Parkinson’s, and we encourage people living with Parkinson’s to incorporate exercise as part of their approach to managing their health,” Dr. Lee said in an interview.

Funding for the project is provided in part by a National Science and Engineering Research Council Discovery Grant and by donations from the Irpinia Club of Toronto and others. Dr. Dr. DeSouza, Ms. Bearss, Dr. Kogutek, and Dr. Lee disclosed no relevant financial relationships.

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

Dancing helps slow the progression of motor and nonmotor symptoms and improves quality of life for patients with Parkinson’s disease (PD), new research shows.

Over 3 years, weekly participation in dance training classes “drastically” reduced the expected decline in motor function and significantly improved speech, tremors, balance, and stiffness, the researchers reported.

Dance training also appeared to have benefits regarding cognition, hallucinations, depression, and anxiety.

“These findings strongly suggest the benefits of dance for people with PD as a supplement to a normal treatment regimen,” the investigators noted.

Although the mechanism of benefit is unclear, dance training may help “train neural network nodes that helps either strengthen networks damaged or builds neural road maps that pass the damage,” study investigator Joseph DeSouza, PhD, principal investigator and associate professor, department of psychology, York University, Toronto, said in an interview.

The study was published online July 7, 2021, in Brain Sciences.
 

Multiple benefits

PD is a neurodegenerative disease associated with progression of motor dysfunction within the first 5 years of diagnosis. The annual rate of motor decline, as determined with the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), is between 5.2 and 8.9 points.

Prior studies that assessed various styles of dance by patients with PD showed beneficial effects regarding gait speed, balance, locomotion, and aspects of quality of life.

To investigate further, DeSouza and coauthor Karolina Bearss, a PhD candidate at York University, followed 16 patients with mild to moderate PD who participated in a weekly dance class at Canada’s National Ballet School and Trinity St. Paul’s church.

Dance for Parkinson’s Disease, which is an established dance curriculum, involves aerobic and anaerobic movements. The protocol begins with a seated warm-up, followed by barre work, and ends with moving across the floor. All participants learn choreography for an upcoming performance.

In the study, 16 patients with PD who did not participant in the dance classes served as control patients.

Over 3 years, the daily rate of motor decline, as indicated by scores on part III of the MDS-UPDRS, was zero among the dancers (slope = 0.000146), indicating no motor impairment, whereas among the nondancers, the motor decline during follow-up was as expected (P < .01), the researchers reported.

In modeling the data, the researchers determined that after completing 1,000 days of dance training, dancers will have a motor score of 19.07, compared with a score of 28.27 for nondancers.

“Our data further showed that training in dance will slow the rate of PD motor impairment progression, as measured by the UPDRS III, by close to 3 points annually in comparison to our PD subjects who did not train,” the researchers reported.

Dance training also had a beneficial effect on motor or nonmotor aspects of daily living and on motor complications, for which there was no significant decline among the PD dancers.

“For those with Parkinson’s disease, even when it’s mild, motor impairment can impact their daily functioning – how they feel about themselves. Many of these motor symptoms lead to isolation because once they get extreme, these people don’t want to go out,” Dr. DeSouza said in a news release.

“These motor symptoms lead to further psychological issues, depression, social isolation and eventually the symptoms do get worse over time. Our study shows that training with dance and music can slow this down and improve their daily living and daily function,” he added.
 

‘Great potential’

Reached for comment, Demian Kogutek, PhD, director of music therapy, University of Evansville (Indiana), said that these preliminary findings from a longitudinal study are “promising.”

“I believe that dance therapy has a great potential for PD. The longitudinal aspect of this study undoubtedly adds to the current literature. Although it is a standardized assessment, it is somewhat subjective,” Dr. Kogutek said in an interview.

Going forward, Dr. Kogutek said he’d like to see other objective outcomes measured, such as objective assessments of balance, gait, hand strength, and dexterity.

Also weighing in on the results, Karen Lee, PhD, president and CEO of Parkinson Canada, said her organization is “encouraged by these preliminary findings as exercise and healthy activities are important for people with Parkinson’s. This study is part of a growing body of research that explores the link between the impact of activities and both motor and nonmotor symptoms of Parkinson’s.

“This research adds to growing evidence about the importance of exercise as part of the management of Parkinson’s, and we encourage people living with Parkinson’s to incorporate exercise as part of their approach to managing their health,” Dr. Lee said in an interview.

Funding for the project is provided in part by a National Science and Engineering Research Council Discovery Grant and by donations from the Irpinia Club of Toronto and others. Dr. Dr. DeSouza, Ms. Bearss, Dr. Kogutek, and Dr. Lee disclosed no relevant financial relationships.

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

Excessive drooling by patients with advanced Parkinson’s disease is an indicator of greater motor and nonmotor dysfunction, new research shows. “Sialorrhea is not just a cosmetic problem,” study investigator Francesca Morgante, MD, associate professor of neurology, St. George’s University, London, told this news organization.

“We need to understand the relationship between sialorrhea and these speech and swallowing disturbances and whether treatment for sialorrhea improves that,” Dr. Morgante added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

Underrecognized symptom

Sialorrhea is an underrecognized nonmotor symptom that can affect up to 70% of patients with Parkinson’s disease, said co-investigator Ioana Cociasu, PhD, postdoctoral research fellow, Neurosciences Research Center, St. George’s University. The impact on quality of life increases with disease severity, she said.

The current study included 101 consecutive patients attending an advanced Parkinson’s disease disorders clinic. Researchers collected demographic data that included information on gender, age, age at Parkinson’s disease onset, and disease duration. They also gathered data on motor symptoms by assessing total levodopa equivalent daily dose (LEDD) and LEDD dopamine agonists. They also assessed results on the Unified Parkinson’s Disease Rating Scale (UPDRS) part III and the Hoehn and Yahr scale for on- and off-medication states.

Nonmotor functioning was assessed using the Non-Motor Symptoms Scale (NMSS) and Scales for Outcomes in Parkinson’s disease–autonomic dysfunction (SCOPA-AUT) questionnaire. Among patients with Parkinson’s disease, autonomic dysfunction can precede motor impairment and can involve orthostatic and postprandial hypotension, among other symptoms, the investigators noted.

Health status and quality of life were assessed using the Parkinson’s disease questionnaire–39 items (PDQ-39). The Radboud Oral Motor Inventory for PD (ROMP) was used to measure orofacial symptoms. ROMP is a self-administered questionnaire that evaluates speech, swallowing disturbances, and drooling of saliva. The Montreal Cognitive Assessment test was also used.

Investigators compared participants with sialorrhea to those without sialorrhea, described as droolers and nondroolers. Droolers were defined as those scoring higher than 1 on the UPDRS-II item 6. This signified slight but definite presence of saliva in the mouth and/or the possibility of nighttime drooling.
 

Greater impairment

Among the participants, 65 (64.4%) were classified as droolers, and 36 (35.6%) as nondroolers.

Patients with both Parkinson’s disease and sialorrhea were significantly more impaired in terms of motor functioning than those without sialorrhea. In these patients, the UPDRS-III was more severe in both the off- (P = .03) and on-states (P = .002), and they had less improvement with the levodopa challenge test (P = .007).

Droolers were also more severely affected by nonmotor problems. They had more severe speech dysfunction (P < .0001) and swallowing dysfunction (P < .05), and they had higher scores on the NMSS (P = .0008) and SCOPA-AUT (P = .003) and poorer quality-of-life scores on the PDQ-39 (P = .049).

To evaluate respiratory tract infections, the researchers used electronic health records. About 15.4% of the study population had had a documented respiratory infection since they were diagnosed with Parkinson’s disease.

Upper and lower respiratory tract infections were more frequent among droolers than nondroolers (P = .05).

“Infections might arise from swallowing disturbances leading to aspiration and drooling,” Dr. Morgante noted.

The drooling did not appear to affect cognition or sleep in these patients.
 

Treatment options?

Following the study presentation, session co-chair Philippe G. Damier, MD, PhD, professor of neurology, University Hospital, Nantes, France, asked about the best treatment for sialorrhea for these patients.

In general, those with milder disease might try chewing gum to improve swallowing; patients with more severe cases may benefit from botulinum toxin injections, said Dr. Cociasu. The treatment choice, she added, “very much depends on the severity of the sialorrhea.”

Botulinum toxin therapy involves injections into the salivary gland to reduce saliva production. It is typically administered about every 4 months.

The second session co-chair, Elena Moro, MD, PhD, director of the Movement Disorders Unit at Grenoble Alpes University, France, pointed out that chewing gum may be a swallowing hazard for patients with PD and severe dementia.

Asked by Dr. Moro whether patients with higher scores on balance and posture were more likely to have sialorrhea, Dr. Cociasu said she and her colleagues are currently looking into this.

Dr. Morgante said that the current study did not examine the effect of treatment on speech disorders associated with sialorrhea. “We are running another study now to understand the effect of treatment of sialorrhea on these features,” she said.

Dr. Morgante and Dr. Cociasu have reported no relevant financial relationships.

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

Excessive drooling by patients with advanced Parkinson’s disease is an indicator of greater motor and nonmotor dysfunction, new research shows. “Sialorrhea is not just a cosmetic problem,” study investigator Francesca Morgante, MD, associate professor of neurology, St. George’s University, London, told this news organization.

“We need to understand the relationship between sialorrhea and these speech and swallowing disturbances and whether treatment for sialorrhea improves that,” Dr. Morgante added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

Underrecognized symptom

Sialorrhea is an underrecognized nonmotor symptom that can affect up to 70% of patients with Parkinson’s disease, said co-investigator Ioana Cociasu, PhD, postdoctoral research fellow, Neurosciences Research Center, St. George’s University. The impact on quality of life increases with disease severity, she said.

The current study included 101 consecutive patients attending an advanced Parkinson’s disease disorders clinic. Researchers collected demographic data that included information on gender, age, age at Parkinson’s disease onset, and disease duration. They also gathered data on motor symptoms by assessing total levodopa equivalent daily dose (LEDD) and LEDD dopamine agonists. They also assessed results on the Unified Parkinson’s Disease Rating Scale (UPDRS) part III and the Hoehn and Yahr scale for on- and off-medication states.

Nonmotor functioning was assessed using the Non-Motor Symptoms Scale (NMSS) and Scales for Outcomes in Parkinson’s disease–autonomic dysfunction (SCOPA-AUT) questionnaire. Among patients with Parkinson’s disease, autonomic dysfunction can precede motor impairment and can involve orthostatic and postprandial hypotension, among other symptoms, the investigators noted.

Health status and quality of life were assessed using the Parkinson’s disease questionnaire–39 items (PDQ-39). The Radboud Oral Motor Inventory for PD (ROMP) was used to measure orofacial symptoms. ROMP is a self-administered questionnaire that evaluates speech, swallowing disturbances, and drooling of saliva. The Montreal Cognitive Assessment test was also used.

Investigators compared participants with sialorrhea to those without sialorrhea, described as droolers and nondroolers. Droolers were defined as those scoring higher than 1 on the UPDRS-II item 6. This signified slight but definite presence of saliva in the mouth and/or the possibility of nighttime drooling.
 

Greater impairment

Among the participants, 65 (64.4%) were classified as droolers, and 36 (35.6%) as nondroolers.

Patients with both Parkinson’s disease and sialorrhea were significantly more impaired in terms of motor functioning than those without sialorrhea. In these patients, the UPDRS-III was more severe in both the off- (P = .03) and on-states (P = .002), and they had less improvement with the levodopa challenge test (P = .007).

Droolers were also more severely affected by nonmotor problems. They had more severe speech dysfunction (P < .0001) and swallowing dysfunction (P < .05), and they had higher scores on the NMSS (P = .0008) and SCOPA-AUT (P = .003) and poorer quality-of-life scores on the PDQ-39 (P = .049).

To evaluate respiratory tract infections, the researchers used electronic health records. About 15.4% of the study population had had a documented respiratory infection since they were diagnosed with Parkinson’s disease.

Upper and lower respiratory tract infections were more frequent among droolers than nondroolers (P = .05).

“Infections might arise from swallowing disturbances leading to aspiration and drooling,” Dr. Morgante noted.

The drooling did not appear to affect cognition or sleep in these patients.
 

Treatment options?

Following the study presentation, session co-chair Philippe G. Damier, MD, PhD, professor of neurology, University Hospital, Nantes, France, asked about the best treatment for sialorrhea for these patients.

In general, those with milder disease might try chewing gum to improve swallowing; patients with more severe cases may benefit from botulinum toxin injections, said Dr. Cociasu. The treatment choice, she added, “very much depends on the severity of the sialorrhea.”

Botulinum toxin therapy involves injections into the salivary gland to reduce saliva production. It is typically administered about every 4 months.

The second session co-chair, Elena Moro, MD, PhD, director of the Movement Disorders Unit at Grenoble Alpes University, France, pointed out that chewing gum may be a swallowing hazard for patients with PD and severe dementia.

Asked by Dr. Moro whether patients with higher scores on balance and posture were more likely to have sialorrhea, Dr. Cociasu said she and her colleagues are currently looking into this.

Dr. Morgante said that the current study did not examine the effect of treatment on speech disorders associated with sialorrhea. “We are running another study now to understand the effect of treatment of sialorrhea on these features,” she said.

Dr. Morgante and Dr. Cociasu have reported no relevant financial relationships.

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

Excessive drooling by patients with advanced Parkinson’s disease is an indicator of greater motor and nonmotor dysfunction, new research shows. “Sialorrhea is not just a cosmetic problem,” study investigator Francesca Morgante, MD, associate professor of neurology, St. George’s University, London, told this news organization.

“We need to understand the relationship between sialorrhea and these speech and swallowing disturbances and whether treatment for sialorrhea improves that,” Dr. Morgante added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

Underrecognized symptom

Sialorrhea is an underrecognized nonmotor symptom that can affect up to 70% of patients with Parkinson’s disease, said co-investigator Ioana Cociasu, PhD, postdoctoral research fellow, Neurosciences Research Center, St. George’s University. The impact on quality of life increases with disease severity, she said.

The current study included 101 consecutive patients attending an advanced Parkinson’s disease disorders clinic. Researchers collected demographic data that included information on gender, age, age at Parkinson’s disease onset, and disease duration. They also gathered data on motor symptoms by assessing total levodopa equivalent daily dose (LEDD) and LEDD dopamine agonists. They also assessed results on the Unified Parkinson’s Disease Rating Scale (UPDRS) part III and the Hoehn and Yahr scale for on- and off-medication states.

Nonmotor functioning was assessed using the Non-Motor Symptoms Scale (NMSS) and Scales for Outcomes in Parkinson’s disease–autonomic dysfunction (SCOPA-AUT) questionnaire. Among patients with Parkinson’s disease, autonomic dysfunction can precede motor impairment and can involve orthostatic and postprandial hypotension, among other symptoms, the investigators noted.

Health status and quality of life were assessed using the Parkinson’s disease questionnaire–39 items (PDQ-39). The Radboud Oral Motor Inventory for PD (ROMP) was used to measure orofacial symptoms. ROMP is a self-administered questionnaire that evaluates speech, swallowing disturbances, and drooling of saliva. The Montreal Cognitive Assessment test was also used.

Investigators compared participants with sialorrhea to those without sialorrhea, described as droolers and nondroolers. Droolers were defined as those scoring higher than 1 on the UPDRS-II item 6. This signified slight but definite presence of saliva in the mouth and/or the possibility of nighttime drooling.
 

Greater impairment

Among the participants, 65 (64.4%) were classified as droolers, and 36 (35.6%) as nondroolers.

Patients with both Parkinson’s disease and sialorrhea were significantly more impaired in terms of motor functioning than those without sialorrhea. In these patients, the UPDRS-III was more severe in both the off- (P = .03) and on-states (P = .002), and they had less improvement with the levodopa challenge test (P = .007).

Droolers were also more severely affected by nonmotor problems. They had more severe speech dysfunction (P < .0001) and swallowing dysfunction (P < .05), and they had higher scores on the NMSS (P = .0008) and SCOPA-AUT (P = .003) and poorer quality-of-life scores on the PDQ-39 (P = .049).

To evaluate respiratory tract infections, the researchers used electronic health records. About 15.4% of the study population had had a documented respiratory infection since they were diagnosed with Parkinson’s disease.

Upper and lower respiratory tract infections were more frequent among droolers than nondroolers (P = .05).

“Infections might arise from swallowing disturbances leading to aspiration and drooling,” Dr. Morgante noted.

The drooling did not appear to affect cognition or sleep in these patients.
 

Treatment options?

Following the study presentation, session co-chair Philippe G. Damier, MD, PhD, professor of neurology, University Hospital, Nantes, France, asked about the best treatment for sialorrhea for these patients.

In general, those with milder disease might try chewing gum to improve swallowing; patients with more severe cases may benefit from botulinum toxin injections, said Dr. Cociasu. The treatment choice, she added, “very much depends on the severity of the sialorrhea.”

Botulinum toxin therapy involves injections into the salivary gland to reduce saliva production. It is typically administered about every 4 months.

The second session co-chair, Elena Moro, MD, PhD, director of the Movement Disorders Unit at Grenoble Alpes University, France, pointed out that chewing gum may be a swallowing hazard for patients with PD and severe dementia.

Asked by Dr. Moro whether patients with higher scores on balance and posture were more likely to have sialorrhea, Dr. Cociasu said she and her colleagues are currently looking into this.

Dr. Morgante said that the current study did not examine the effect of treatment on speech disorders associated with sialorrhea. “We are running another study now to understand the effect of treatment of sialorrhea on these features,” she said.

Dr. Morgante and Dr. Cociasu have reported no relevant financial relationships.

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

About one-third of individuals with adult-onset idiopathic dystonia experience major depression or dysthymia, data from a meta-analysis of 54 studies show.

Adult-onset idiopathic dystonia (AOID) is the third-most common movement disorder after essential tremor and Parkinson’s disease, and data show that depression and anxiety are the largest contributors to reduced quality of life in these patients, wrote Alex Medina Escobar, MD, of the University of Calgary (Alta.), and colleagues. However, “the pathogenic mechanisms of depression and anxiety in AOID remain unclear” and might involve a combination of biologic factors, as well as social stigma.

In the meta-analysis, published in Neuroscience and Biobehavioral Reviews, the researchers examined the point prevalence of supraclinical threshold depressive symptoms/depressive disorders in AOID using 54 studies. The resulting study population included 12,635 patients: 6,977 with cervical dystonia, 732 with cranial dystonia, 4,504 with mixed forms, 303 with laryngeal dystonia, and 119 with upper-limb dystonia. The studies were published between 1988 and 2020, and included patients from 21 countries in 52 single-center studies and 2 multicenter studies.

Overall, the pooled prevalence of either supraclinical threshold depressive symptoms or depressive disorders was 31.5% for cervical dystonia, 29.2 % for cranial dystonia, and 33.6 % for clinical samples with mixed forms of AOID.

Among patients with cervical dystonia, major depressive disorder was more prevalent than dysthymia, but among patients with cranial dystonia, dysthymia was more prevalent. Among patients with mixed forms, the prevalence of major depressive disorder was higher than dysthymia. Heterogeneity varied among the studies but was higher in studies that used rating scales.

Treatment of patients with AOID does not take into account the impact of depression on quality of life, Dr. Escobar and colleagues reported.

“The current model of care for AOID remains primarily centered on the treatment of the movement disorder with local injections of botulinum toxin. Such model appears to be inefficient to guarantee resources to address these comorbidities within secondary or tertiary care, or through shared care pathways engaging both primary and hospital-based care.” They also said the use of antidepressants and cognitive-behavioral therapy as a way to target negative body concept or social stigma among these patients are “underexplored and underutilized.”

The study findings were limited by several factors, including the inclusion only of studies published in English. In addition, most of the studies were conducted at movement disorders clinics, which may have yielded a patient population with more severe AOID. Further limitations included the inability to perform subgroup analysis based on demographic and clinical factors, and the insufficient number of studies for meta-analysis of laryngeal and hand dystonia, Dr. Escobar and colleagues added.

However, the results represent the first pooled estimate of depression prevalence in AOID and confirm a high prevalence across different clinical forms, the researchers said. The heterogeneity across studies highlights the need for standardized screening for depression and improved diagnosis of mood disorders in AOID.

“The meta-analytic estimates provided here will be highly useful for the planning of future mechanistic and interventional studies, as well as for the redefinition of current models of care,” they concluded.

The study received no outside funding. Dr. Escobar and colleagues had no disclosures.

About one-third of individuals with adult-onset idiopathic dystonia experience major depression or dysthymia, data from a meta-analysis of 54 studies show.

Adult-onset idiopathic dystonia (AOID) is the third-most common movement disorder after essential tremor and Parkinson’s disease, and data show that depression and anxiety are the largest contributors to reduced quality of life in these patients, wrote Alex Medina Escobar, MD, of the University of Calgary (Alta.), and colleagues. However, “the pathogenic mechanisms of depression and anxiety in AOID remain unclear” and might involve a combination of biologic factors, as well as social stigma.

In the meta-analysis, published in Neuroscience and Biobehavioral Reviews, the researchers examined the point prevalence of supraclinical threshold depressive symptoms/depressive disorders in AOID using 54 studies. The resulting study population included 12,635 patients: 6,977 with cervical dystonia, 732 with cranial dystonia, 4,504 with mixed forms, 303 with laryngeal dystonia, and 119 with upper-limb dystonia. The studies were published between 1988 and 2020, and included patients from 21 countries in 52 single-center studies and 2 multicenter studies.

Overall, the pooled prevalence of either supraclinical threshold depressive symptoms or depressive disorders was 31.5% for cervical dystonia, 29.2 % for cranial dystonia, and 33.6 % for clinical samples with mixed forms of AOID.

Among patients with cervical dystonia, major depressive disorder was more prevalent than dysthymia, but among patients with cranial dystonia, dysthymia was more prevalent. Among patients with mixed forms, the prevalence of major depressive disorder was higher than dysthymia. Heterogeneity varied among the studies but was higher in studies that used rating scales.

Treatment of patients with AOID does not take into account the impact of depression on quality of life, Dr. Escobar and colleagues reported.

“The current model of care for AOID remains primarily centered on the treatment of the movement disorder with local injections of botulinum toxin. Such model appears to be inefficient to guarantee resources to address these comorbidities within secondary or tertiary care, or through shared care pathways engaging both primary and hospital-based care.” They also said the use of antidepressants and cognitive-behavioral therapy as a way to target negative body concept or social stigma among these patients are “underexplored and underutilized.”

The study findings were limited by several factors, including the inclusion only of studies published in English. In addition, most of the studies were conducted at movement disorders clinics, which may have yielded a patient population with more severe AOID. Further limitations included the inability to perform subgroup analysis based on demographic and clinical factors, and the insufficient number of studies for meta-analysis of laryngeal and hand dystonia, Dr. Escobar and colleagues added.

However, the results represent the first pooled estimate of depression prevalence in AOID and confirm a high prevalence across different clinical forms, the researchers said. The heterogeneity across studies highlights the need for standardized screening for depression and improved diagnosis of mood disorders in AOID.

“The meta-analytic estimates provided here will be highly useful for the planning of future mechanistic and interventional studies, as well as for the redefinition of current models of care,” they concluded.

The study received no outside funding. Dr. Escobar and colleagues had no disclosures.

About one-third of individuals with adult-onset idiopathic dystonia experience major depression or dysthymia, data from a meta-analysis of 54 studies show.

Adult-onset idiopathic dystonia (AOID) is the third-most common movement disorder after essential tremor and Parkinson’s disease, and data show that depression and anxiety are the largest contributors to reduced quality of life in these patients, wrote Alex Medina Escobar, MD, of the University of Calgary (Alta.), and colleagues. However, “the pathogenic mechanisms of depression and anxiety in AOID remain unclear” and might involve a combination of biologic factors, as well as social stigma.

In the meta-analysis, published in Neuroscience and Biobehavioral Reviews, the researchers examined the point prevalence of supraclinical threshold depressive symptoms/depressive disorders in AOID using 54 studies. The resulting study population included 12,635 patients: 6,977 with cervical dystonia, 732 with cranial dystonia, 4,504 with mixed forms, 303 with laryngeal dystonia, and 119 with upper-limb dystonia. The studies were published between 1988 and 2020, and included patients from 21 countries in 52 single-center studies and 2 multicenter studies.

Overall, the pooled prevalence of either supraclinical threshold depressive symptoms or depressive disorders was 31.5% for cervical dystonia, 29.2 % for cranial dystonia, and 33.6 % for clinical samples with mixed forms of AOID.

Among patients with cervical dystonia, major depressive disorder was more prevalent than dysthymia, but among patients with cranial dystonia, dysthymia was more prevalent. Among patients with mixed forms, the prevalence of major depressive disorder was higher than dysthymia. Heterogeneity varied among the studies but was higher in studies that used rating scales.

Treatment of patients with AOID does not take into account the impact of depression on quality of life, Dr. Escobar and colleagues reported.

“The current model of care for AOID remains primarily centered on the treatment of the movement disorder with local injections of botulinum toxin. Such model appears to be inefficient to guarantee resources to address these comorbidities within secondary or tertiary care, or through shared care pathways engaging both primary and hospital-based care.” They also said the use of antidepressants and cognitive-behavioral therapy as a way to target negative body concept or social stigma among these patients are “underexplored and underutilized.”

The study findings were limited by several factors, including the inclusion only of studies published in English. In addition, most of the studies were conducted at movement disorders clinics, which may have yielded a patient population with more severe AOID. Further limitations included the inability to perform subgroup analysis based on demographic and clinical factors, and the insufficient number of studies for meta-analysis of laryngeal and hand dystonia, Dr. Escobar and colleagues added.

However, the results represent the first pooled estimate of depression prevalence in AOID and confirm a high prevalence across different clinical forms, the researchers said. The heterogeneity across studies highlights the need for standardized screening for depression and improved diagnosis of mood disorders in AOID.

“The meta-analytic estimates provided here will be highly useful for the planning of future mechanistic and interventional studies, as well as for the redefinition of current models of care,” they concluded.

The study received no outside funding. Dr. Escobar and colleagues had no disclosures.

Managing depression and anxiety in Parkinson’s disease should start with a review of medications and involve multidisciplinary care, according to a recent summary of evidence.

“Depression and anxiety have a complex relationship with the disease and while the exact mechanism for this association is unknown, both disturbances occur with increased prevalence across the disease course and when present earlier in life, increase the risk of PD by about twofold,” wrote Gregory M. Pontone, MD, of Johns Hopkins University, Baltimore, and colleagues.

Randomized trials to guide treatment of anxiety and depression in patients with Parkinson’s disease (PD) are limited, the researchers noted. However, data from a longitudinal study showed that PD patients whose depression remitted spontaneously or responded to treatment were able to attain a level of function similar to that of never-depressed PD patients, Dr. Pontone and colleagues said.

The researchers offered a pair of treatment algorithms to help guide clinicians in managing depression and anxiety in PD. However, a caveat to keep in mind is that “the benefit of antidepressant medications, used for depression or anxiety, can be confounded when motor symptoms are not optimally treated,” the researchers emphasized.

For depression, the researchers advised starting with some lab work; “at a minimum we suggest checking a complete blood count, metabolic panel, TSH, B12, and folate,” they noted. They recommended an antidepressant, cognitive-behavioral therapy, or both, as a first-line treatment, such as monotherapy with selective norepinephrine reuptake inhibitors or selective serotonin reuptake inhibitors. They advised titrating the chosen monotherapy to a minimum effective dose over a 2- to 3-week period to assess response.

“We recommend continuing antidepressant therapy for at least 1 year based on literature in non-PD populations and anecdotal clinical experience. At 1 year, if not in remission, consider continuing treatment or augmenting to improve response,” the researchers said.

Based on the current DSM-5 criteria, up to one-third of PD patients have an unspecified anxiety disorder, the researchers said, and they recommended using anxiety rating scales to diagnose anxiety in PD. “Given the high prevalence of atypical anxiety syndromes in PD and their potential association with both motor and nonmotor symptoms of the disease, working with the neurologist to achieve optimal control of PD is an essential first step to alleviating anxiety,” they emphasized.

The researchers also advised addressing comorbidities, including cardiovascular disease, chronic pain, diabetes, gastrointestinal issues, hyperthyroidism, and lung disease, all of which can be associated with anxiety. Once comorbidities are addressed, they advised caution given the lack of evidence for efficacy of both pharmacologic and nonpharmacologic anxiety treatments for PD patients. However, first-tier treatment for anxiety could include monotherapy with serotonin-norepinephrine reuptake inhibitors or selective serotonin reuptake inhibitors, they said.

PD patients with depression and anxiety also may benefit from nonpharmacologic interventions, including exercise, mindfulness, relaxation therapy, and cognitive behavioral therapy the researchers said.

Although the algorithm may not differ significantly from current treatment protocols, it highlights aspects unique to PD patients, the researchers said. In particular, the algorithm shows “that interventions used for motor symptoms, for example, dopamine agonists, may be especially potent for mood in the PD population and that augmentation strategies, such as antipsychotics and lithium, may not be well tolerated given their outsized risk of adverse events in PD,” they said.

“While an article of this kind cannot hope to address the gap in knowledge on comparative efficacy between interventions, it can guide readers on the best strategies for implementation and risk mitigation in PD – essentially focusing more on effectiveness,” they concluded.

The study received no outside funding. Dr. Pontone disclosed serving as a consultant for Acadia Pharmaceuticals and Concert Pharmaceuticals.

Managing depression and anxiety in Parkinson’s disease should start with a review of medications and involve multidisciplinary care, according to a recent summary of evidence.

“Depression and anxiety have a complex relationship with the disease and while the exact mechanism for this association is unknown, both disturbances occur with increased prevalence across the disease course and when present earlier in life, increase the risk of PD by about twofold,” wrote Gregory M. Pontone, MD, of Johns Hopkins University, Baltimore, and colleagues.

Randomized trials to guide treatment of anxiety and depression in patients with Parkinson’s disease (PD) are limited, the researchers noted. However, data from a longitudinal study showed that PD patients whose depression remitted spontaneously or responded to treatment were able to attain a level of function similar to that of never-depressed PD patients, Dr. Pontone and colleagues said.

The researchers offered a pair of treatment algorithms to help guide clinicians in managing depression and anxiety in PD. However, a caveat to keep in mind is that “the benefit of antidepressant medications, used for depression or anxiety, can be confounded when motor symptoms are not optimally treated,” the researchers emphasized.

For depression, the researchers advised starting with some lab work; “at a minimum we suggest checking a complete blood count, metabolic panel, TSH, B12, and folate,” they noted. They recommended an antidepressant, cognitive-behavioral therapy, or both, as a first-line treatment, such as monotherapy with selective norepinephrine reuptake inhibitors or selective serotonin reuptake inhibitors. They advised titrating the chosen monotherapy to a minimum effective dose over a 2- to 3-week period to assess response.

“We recommend continuing antidepressant therapy for at least 1 year based on literature in non-PD populations and anecdotal clinical experience. At 1 year, if not in remission, consider continuing treatment or augmenting to improve response,” the researchers said.

Based on the current DSM-5 criteria, up to one-third of PD patients have an unspecified anxiety disorder, the researchers said, and they recommended using anxiety rating scales to diagnose anxiety in PD. “Given the high prevalence of atypical anxiety syndromes in PD and their potential association with both motor and nonmotor symptoms of the disease, working with the neurologist to achieve optimal control of PD is an essential first step to alleviating anxiety,” they emphasized.

The researchers also advised addressing comorbidities, including cardiovascular disease, chronic pain, diabetes, gastrointestinal issues, hyperthyroidism, and lung disease, all of which can be associated with anxiety. Once comorbidities are addressed, they advised caution given the lack of evidence for efficacy of both pharmacologic and nonpharmacologic anxiety treatments for PD patients. However, first-tier treatment for anxiety could include monotherapy with serotonin-norepinephrine reuptake inhibitors or selective serotonin reuptake inhibitors, they said.

PD patients with depression and anxiety also may benefit from nonpharmacologic interventions, including exercise, mindfulness, relaxation therapy, and cognitive behavioral therapy the researchers said.

Although the algorithm may not differ significantly from current treatment protocols, it highlights aspects unique to PD patients, the researchers said. In particular, the algorithm shows “that interventions used for motor symptoms, for example, dopamine agonists, may be especially potent for mood in the PD population and that augmentation strategies, such as antipsychotics and lithium, may not be well tolerated given their outsized risk of adverse events in PD,” they said.

“While an article of this kind cannot hope to address the gap in knowledge on comparative efficacy between interventions, it can guide readers on the best strategies for implementation and risk mitigation in PD – essentially focusing more on effectiveness,” they concluded.

The study received no outside funding. Dr. Pontone disclosed serving as a consultant for Acadia Pharmaceuticals and Concert Pharmaceuticals.

Managing depression and anxiety in Parkinson’s disease should start with a review of medications and involve multidisciplinary care, according to a recent summary of evidence.

“Depression and anxiety have a complex relationship with the disease and while the exact mechanism for this association is unknown, both disturbances occur with increased prevalence across the disease course and when present earlier in life, increase the risk of PD by about twofold,” wrote Gregory M. Pontone, MD, of Johns Hopkins University, Baltimore, and colleagues.

Randomized trials to guide treatment of anxiety and depression in patients with Parkinson’s disease (PD) are limited, the researchers noted. However, data from a longitudinal study showed that PD patients whose depression remitted spontaneously or responded to treatment were able to attain a level of function similar to that of never-depressed PD patients, Dr. Pontone and colleagues said.

The researchers offered a pair of treatment algorithms to help guide clinicians in managing depression and anxiety in PD. However, a caveat to keep in mind is that “the benefit of antidepressant medications, used for depression or anxiety, can be confounded when motor symptoms are not optimally treated,” the researchers emphasized.

For depression, the researchers advised starting with some lab work; “at a minimum we suggest checking a complete blood count, metabolic panel, TSH, B12, and folate,” they noted. They recommended an antidepressant, cognitive-behavioral therapy, or both, as a first-line treatment, such as monotherapy with selective norepinephrine reuptake inhibitors or selective serotonin reuptake inhibitors. They advised titrating the chosen monotherapy to a minimum effective dose over a 2- to 3-week period to assess response.

“We recommend continuing antidepressant therapy for at least 1 year based on literature in non-PD populations and anecdotal clinical experience. At 1 year, if not in remission, consider continuing treatment or augmenting to improve response,” the researchers said.

Based on the current DSM-5 criteria, up to one-third of PD patients have an unspecified anxiety disorder, the researchers said, and they recommended using anxiety rating scales to diagnose anxiety in PD. “Given the high prevalence of atypical anxiety syndromes in PD and their potential association with both motor and nonmotor symptoms of the disease, working with the neurologist to achieve optimal control of PD is an essential first step to alleviating anxiety,” they emphasized.

The researchers also advised addressing comorbidities, including cardiovascular disease, chronic pain, diabetes, gastrointestinal issues, hyperthyroidism, and lung disease, all of which can be associated with anxiety. Once comorbidities are addressed, they advised caution given the lack of evidence for efficacy of both pharmacologic and nonpharmacologic anxiety treatments for PD patients. However, first-tier treatment for anxiety could include monotherapy with serotonin-norepinephrine reuptake inhibitors or selective serotonin reuptake inhibitors, they said.

PD patients with depression and anxiety also may benefit from nonpharmacologic interventions, including exercise, mindfulness, relaxation therapy, and cognitive behavioral therapy the researchers said.

Although the algorithm may not differ significantly from current treatment protocols, it highlights aspects unique to PD patients, the researchers said. In particular, the algorithm shows “that interventions used for motor symptoms, for example, dopamine agonists, may be especially potent for mood in the PD population and that augmentation strategies, such as antipsychotics and lithium, may not be well tolerated given their outsized risk of adverse events in PD,” they said.

“While an article of this kind cannot hope to address the gap in knowledge on comparative efficacy between interventions, it can guide readers on the best strategies for implementation and risk mitigation in PD – essentially focusing more on effectiveness,” they concluded.

The study received no outside funding. Dr. Pontone disclosed serving as a consultant for Acadia Pharmaceuticals and Concert Pharmaceuticals.

Advances in photobiomodulation have propelled the use of therapeutic applications in a variety of medical specialties, according to Juanita J. Anders, PhD.

During the annual conference of the American Society for Laser Medicine and Surgery, Dr. Anders, professor of anatomy, physiology, and genetics at the Uniformed Services University of the Health Sciences, Bethesda, Md., defined photobiomodulation (PBM) as the mechanism by which nonionizing optical radiation in the visible and near-infrared spectral range is absorbed by endogenous chromophores to elicit photophysical and photochemical events at various biological scales. Photobiomodulation therapy (PBMT) involves the use of light sources including lasers, LEDs, and broadband light, that emit visible and/or near-infrared light to cause physiological changes in cells and tissues and result in therapeutic benefits.

In dermatology, LED light therapy devices are commonly used for PBMT in wavelengths that range from blue (415 nm) and red (633 nm) to near infrared (830 nm). “Often, when PBMT is referred to by dermatologists it’s called LED therapy or LED light therapy,” Dr. Anders noted. “Some people are under the impression that this is different from PBMT. But remember: It’s not the device that’s producing the photons that is clinically relevant, but it’s the photons themselves. In both cases, the same radiances and fluence ranges are being used and the mechanisms are the same, so it’s all PBMT.”

The therapy is used to treat a wide variety of medical and aesthetic disorders including acne vulgaris, psoriasis, burns, and wound healing. It has also been used in conjunction with surgical aesthetic and resurfacing procedures and has been reported to reduce erythema, edema, bruising, and days to healing. It’s been shown that PBMT stimulates fibroblast proliferation, collagen synthesis, and extracellular matrix resulting in lifting and tightening lax skin.

According to Dr. Anders, French dermatologists Linda Fouque, MD, and Michele Pelletier, MD, performed a series of in vivo and in vitro studies in which they tested the effects of yellow and red light for skin rejuvenation when used individually or in combination. “They found that fibroblasts and keratinocytes in vitro had great improvement in their morphology both with the yellow and red light, but the best improvement was seen with combination therapy,” Dr. Anders said. “This held true in their work looking at epidermal and dermal markers in the skin, where they found the best up-regulation in protein synthesis of such markers as collagens and fibronectin were produced when a combination wavelength light was used.”

Oral mucositis and pain

PBMT is also being used to treat oral mucositis (OM), a common adverse response to chemotherapy and/or radiation therapy, which causes pain, difficulty in swallowing and eating, and oral ulceration, and often interrupts the course of treatments. Authors of a recently published review on the risks and benefits of PBMT concluded that there is consistent evidence from a small number of high-quality studies that PBMT can help prevent the development of cancer therapy–induced OM, reduce pain intensity, as well as promote healing, and enhance patient quality of life.

“They also cautioned that, due to the limited long-term follow-up of patients, there is still concern for the potential long-term risks of PBMT in cancer cell mutation and amplification,” Dr. Anders said. “They advised that PBMT should be used carefully when the irradiation beam is in the direction of the tumor zone.”

Using PBMT for modulation of pain is another area of active research. Based on work from the laboratory of Dr. Anders and others, there are two methods to modulate pain. The first is to target tissue at irradiances below 100 mW/cm².

“In my laboratory, based on in vivo preclinical animal models of neuropathic pain, we used a 980-nm wavelength laser at 43.25 mW/cm² transcutaneously delivered to the level of the nerve for 20 seconds,” said Dr. Anders, who is a past president of the ASLMS. “Essentially, we found that the pain was modulated by reducing sensitivity to mechanical stimulation and also by causing an anti-inflammatory shift in microglial and macrophage phenotype in the dorsal root ganglion and spinal cord of affected segments.”

The second way to modulate pain, she continued, is to target tissue at irradiances above 250 mW/cm². She and her colleagues have conducted in vitro and in vivo studies, which indicate that treatment with an irradiance/fluence rate at 270 mW/cm² or higher at the nerve can rapidly block pain transmission.

“In vitro, we found that if we used an 810-nm wavelength light at 300 mW/cm², we got a disruption of microtubules in the DRG neurons in culture, specifically the small neurons, the nociceptive fibers, but we did not affect the proprioceptive fibers unless we increased the length of the treatment,” she said. “We essentially found the same thing in vivo in a rodent model of neuropathic pain.”

In a pilot study, Dr. Anders and coauthors examined the efficacy of laser irradiation of the dorsal root ganglion of the second lumbar spinal nerve for patients with chronic back pain.

They found that PBMT effectively reduced back pain equal to the effects of lidocaine.

Based on these two irradiation approaches of targeting tissue, Dr. Anders recommends that a combination therapy be used to modulate neuropathic pain going forward. “This approach would involve the initial use of a high-irradiance treatment [at least 250 mW/cm²] at the nerve to block the pain transmission,” she said. “That treatment would be followed by a series of low-irradiance treatments [10-100 mW/cm²] along the course of the involved nerve to alter chronic pathology and inflammation.”
 

Potential applications in neurology

Dr. Anders also discussed research efforts under way involving transcranial PBMT: the delivery of near-infrared light through the tissues of the scalp and skull to targeted brain regions to treat neurologic injuries and disorders. “There have been some exciting results in preclinical animal work and in small clinical pilot work that show that there could be possible beneficial effects in Parkinson’s disease, Alzheimer’s disease, depression, and improvement in cognition and memory after a brain injury, such as a TBI,” she said.

“Initially, though, there were a lot of questions about whether you could really deliver light to the brain through the scalp. In my laboratory, we used slices of nonfixed brain and found that the sulci within the human brain act as light-wave guides. We used an 808-nm near-infrared wavelength of light, so that the light could penetrate more deeply.” Using nonfixed cadaver heads, where the light was applied at the scalp surface, Dr. Anders and colleagues were able to measure photons down to the depth of 4 cm. “It’s generally agreed now, though, that it’s to a maximum depth of 2.5-3 cm that enough photons are delivered that would cause a beneficial therapeutic effect,” she said.

Dr. Anders disclosed that she has received equipment from LiteCure, grant funding from the Department of Defense, and that she holds advisory board roles with LiteCure and Neurothera. She has also served in leadership roles for the Optical Society and holds intellectual property rights for the Henry M. Jackson Foundation for the Advancement of Military Medicine.

dbrunk@mdedge.com

Advances in photobiomodulation have propelled the use of therapeutic applications in a variety of medical specialties, according to Juanita J. Anders, PhD.

During the annual conference of the American Society for Laser Medicine and Surgery, Dr. Anders, professor of anatomy, physiology, and genetics at the Uniformed Services University of the Health Sciences, Bethesda, Md., defined photobiomodulation (PBM) as the mechanism by which nonionizing optical radiation in the visible and near-infrared spectral range is absorbed by endogenous chromophores to elicit photophysical and photochemical events at various biological scales. Photobiomodulation therapy (PBMT) involves the use of light sources including lasers, LEDs, and broadband light, that emit visible and/or near-infrared light to cause physiological changes in cells and tissues and result in therapeutic benefits.

In dermatology, LED light therapy devices are commonly used for PBMT in wavelengths that range from blue (415 nm) and red (633 nm) to near infrared (830 nm). “Often, when PBMT is referred to by dermatologists it’s called LED therapy or LED light therapy,” Dr. Anders noted. “Some people are under the impression that this is different from PBMT. But remember: It’s not the device that’s producing the photons that is clinically relevant, but it’s the photons themselves. In both cases, the same radiances and fluence ranges are being used and the mechanisms are the same, so it’s all PBMT.”

The therapy is used to treat a wide variety of medical and aesthetic disorders including acne vulgaris, psoriasis, burns, and wound healing. It has also been used in conjunction with surgical aesthetic and resurfacing procedures and has been reported to reduce erythema, edema, bruising, and days to healing. It’s been shown that PBMT stimulates fibroblast proliferation, collagen synthesis, and extracellular matrix resulting in lifting and tightening lax skin.

According to Dr. Anders, French dermatologists Linda Fouque, MD, and Michele Pelletier, MD, performed a series of in vivo and in vitro studies in which they tested the effects of yellow and red light for skin rejuvenation when used individually or in combination. “They found that fibroblasts and keratinocytes in vitro had great improvement in their morphology both with the yellow and red light, but the best improvement was seen with combination therapy,” Dr. Anders said. “This held true in their work looking at epidermal and dermal markers in the skin, where they found the best up-regulation in protein synthesis of such markers as collagens and fibronectin were produced when a combination wavelength light was used.”

Oral mucositis and pain

PBMT is also being used to treat oral mucositis (OM), a common adverse response to chemotherapy and/or radiation therapy, which causes pain, difficulty in swallowing and eating, and oral ulceration, and often interrupts the course of treatments. Authors of a recently published review on the risks and benefits of PBMT concluded that there is consistent evidence from a small number of high-quality studies that PBMT can help prevent the development of cancer therapy–induced OM, reduce pain intensity, as well as promote healing, and enhance patient quality of life.

“They also cautioned that, due to the limited long-term follow-up of patients, there is still concern for the potential long-term risks of PBMT in cancer cell mutation and amplification,” Dr. Anders said. “They advised that PBMT should be used carefully when the irradiation beam is in the direction of the tumor zone.”

Using PBMT for modulation of pain is another area of active research. Based on work from the laboratory of Dr. Anders and others, there are two methods to modulate pain. The first is to target tissue at irradiances below 100 mW/cm².

“In my laboratory, based on in vivo preclinical animal models of neuropathic pain, we used a 980-nm wavelength laser at 43.25 mW/cm² transcutaneously delivered to the level of the nerve for 20 seconds,” said Dr. Anders, who is a past president of the ASLMS. “Essentially, we found that the pain was modulated by reducing sensitivity to mechanical stimulation and also by causing an anti-inflammatory shift in microglial and macrophage phenotype in the dorsal root ganglion and spinal cord of affected segments.”

The second way to modulate pain, she continued, is to target tissue at irradiances above 250 mW/cm². She and her colleagues have conducted in vitro and in vivo studies, which indicate that treatment with an irradiance/fluence rate at 270 mW/cm² or higher at the nerve can rapidly block pain transmission.

“In vitro, we found that if we used an 810-nm wavelength light at 300 mW/cm², we got a disruption of microtubules in the DRG neurons in culture, specifically the small neurons, the nociceptive fibers, but we did not affect the proprioceptive fibers unless we increased the length of the treatment,” she said. “We essentially found the same thing in vivo in a rodent model of neuropathic pain.”

In a pilot study, Dr. Anders and coauthors examined the efficacy of laser irradiation of the dorsal root ganglion of the second lumbar spinal nerve for patients with chronic back pain.

They found that PBMT effectively reduced back pain equal to the effects of lidocaine.

Based on these two irradiation approaches of targeting tissue, Dr. Anders recommends that a combination therapy be used to modulate neuropathic pain going forward. “This approach would involve the initial use of a high-irradiance treatment [at least 250 mW/cm²] at the nerve to block the pain transmission,” she said. “That treatment would be followed by a series of low-irradiance treatments [10-100 mW/cm²] along the course of the involved nerve to alter chronic pathology and inflammation.”
 

Potential applications in neurology

Dr. Anders also discussed research efforts under way involving transcranial PBMT: the delivery of near-infrared light through the tissues of the scalp and skull to targeted brain regions to treat neurologic injuries and disorders. “There have been some exciting results in preclinical animal work and in small clinical pilot work that show that there could be possible beneficial effects in Parkinson’s disease, Alzheimer’s disease, depression, and improvement in cognition and memory after a brain injury, such as a TBI,” she said.

“Initially, though, there were a lot of questions about whether you could really deliver light to the brain through the scalp. In my laboratory, we used slices of nonfixed brain and found that the sulci within the human brain act as light-wave guides. We used an 808-nm near-infrared wavelength of light, so that the light could penetrate more deeply.” Using nonfixed cadaver heads, where the light was applied at the scalp surface, Dr. Anders and colleagues were able to measure photons down to the depth of 4 cm. “It’s generally agreed now, though, that it’s to a maximum depth of 2.5-3 cm that enough photons are delivered that would cause a beneficial therapeutic effect,” she said.

Dr. Anders disclosed that she has received equipment from LiteCure, grant funding from the Department of Defense, and that she holds advisory board roles with LiteCure and Neurothera. She has also served in leadership roles for the Optical Society and holds intellectual property rights for the Henry M. Jackson Foundation for the Advancement of Military Medicine.

dbrunk@mdedge.com

Advances in photobiomodulation have propelled the use of therapeutic applications in a variety of medical specialties, according to Juanita J. Anders, PhD.

During the annual conference of the American Society for Laser Medicine and Surgery, Dr. Anders, professor of anatomy, physiology, and genetics at the Uniformed Services University of the Health Sciences, Bethesda, Md., defined photobiomodulation (PBM) as the mechanism by which nonionizing optical radiation in the visible and near-infrared spectral range is absorbed by endogenous chromophores to elicit photophysical and photochemical events at various biological scales. Photobiomodulation therapy (PBMT) involves the use of light sources including lasers, LEDs, and broadband light, that emit visible and/or near-infrared light to cause physiological changes in cells and tissues and result in therapeutic benefits.

In dermatology, LED light therapy devices are commonly used for PBMT in wavelengths that range from blue (415 nm) and red (633 nm) to near infrared (830 nm). “Often, when PBMT is referred to by dermatologists it’s called LED therapy or LED light therapy,” Dr. Anders noted. “Some people are under the impression that this is different from PBMT. But remember: It’s not the device that’s producing the photons that is clinically relevant, but it’s the photons themselves. In both cases, the same radiances and fluence ranges are being used and the mechanisms are the same, so it’s all PBMT.”

The therapy is used to treat a wide variety of medical and aesthetic disorders including acne vulgaris, psoriasis, burns, and wound healing. It has also been used in conjunction with surgical aesthetic and resurfacing procedures and has been reported to reduce erythema, edema, bruising, and days to healing. It’s been shown that PBMT stimulates fibroblast proliferation, collagen synthesis, and extracellular matrix resulting in lifting and tightening lax skin.

According to Dr. Anders, French dermatologists Linda Fouque, MD, and Michele Pelletier, MD, performed a series of in vivo and in vitro studies in which they tested the effects of yellow and red light for skin rejuvenation when used individually or in combination. “They found that fibroblasts and keratinocytes in vitro had great improvement in their morphology both with the yellow and red light, but the best improvement was seen with combination therapy,” Dr. Anders said. “This held true in their work looking at epidermal and dermal markers in the skin, where they found the best up-regulation in protein synthesis of such markers as collagens and fibronectin were produced when a combination wavelength light was used.”

Oral mucositis and pain

PBMT is also being used to treat oral mucositis (OM), a common adverse response to chemotherapy and/or radiation therapy, which causes pain, difficulty in swallowing and eating, and oral ulceration, and often interrupts the course of treatments. Authors of a recently published review on the risks and benefits of PBMT concluded that there is consistent evidence from a small number of high-quality studies that PBMT can help prevent the development of cancer therapy–induced OM, reduce pain intensity, as well as promote healing, and enhance patient quality of life.

“They also cautioned that, due to the limited long-term follow-up of patients, there is still concern for the potential long-term risks of PBMT in cancer cell mutation and amplification,” Dr. Anders said. “They advised that PBMT should be used carefully when the irradiation beam is in the direction of the tumor zone.”

Using PBMT for modulation of pain is another area of active research. Based on work from the laboratory of Dr. Anders and others, there are two methods to modulate pain. The first is to target tissue at irradiances below 100 mW/cm².

“In my laboratory, based on in vivo preclinical animal models of neuropathic pain, we used a 980-nm wavelength laser at 43.25 mW/cm² transcutaneously delivered to the level of the nerve for 20 seconds,” said Dr. Anders, who is a past president of the ASLMS. “Essentially, we found that the pain was modulated by reducing sensitivity to mechanical stimulation and also by causing an anti-inflammatory shift in microglial and macrophage phenotype in the dorsal root ganglion and spinal cord of affected segments.”

The second way to modulate pain, she continued, is to target tissue at irradiances above 250 mW/cm². She and her colleagues have conducted in vitro and in vivo studies, which indicate that treatment with an irradiance/fluence rate at 270 mW/cm² or higher at the nerve can rapidly block pain transmission.

“In vitro, we found that if we used an 810-nm wavelength light at 300 mW/cm², we got a disruption of microtubules in the DRG neurons in culture, specifically the small neurons, the nociceptive fibers, but we did not affect the proprioceptive fibers unless we increased the length of the treatment,” she said. “We essentially found the same thing in vivo in a rodent model of neuropathic pain.”

In a pilot study, Dr. Anders and coauthors examined the efficacy of laser irradiation of the dorsal root ganglion of the second lumbar spinal nerve for patients with chronic back pain.

They found that PBMT effectively reduced back pain equal to the effects of lidocaine.

Based on these two irradiation approaches of targeting tissue, Dr. Anders recommends that a combination therapy be used to modulate neuropathic pain going forward. “This approach would involve the initial use of a high-irradiance treatment [at least 250 mW/cm²] at the nerve to block the pain transmission,” she said. “That treatment would be followed by a series of low-irradiance treatments [10-100 mW/cm²] along the course of the involved nerve to alter chronic pathology and inflammation.”
 

Potential applications in neurology

Dr. Anders also discussed research efforts under way involving transcranial PBMT: the delivery of near-infrared light through the tissues of the scalp and skull to targeted brain regions to treat neurologic injuries and disorders. “There have been some exciting results in preclinical animal work and in small clinical pilot work that show that there could be possible beneficial effects in Parkinson’s disease, Alzheimer’s disease, depression, and improvement in cognition and memory after a brain injury, such as a TBI,” she said.

“Initially, though, there were a lot of questions about whether you could really deliver light to the brain through the scalp. In my laboratory, we used slices of nonfixed brain and found that the sulci within the human brain act as light-wave guides. We used an 808-nm near-infrared wavelength of light, so that the light could penetrate more deeply.” Using nonfixed cadaver heads, where the light was applied at the scalp surface, Dr. Anders and colleagues were able to measure photons down to the depth of 4 cm. “It’s generally agreed now, though, that it’s to a maximum depth of 2.5-3 cm that enough photons are delivered that would cause a beneficial therapeutic effect,” she said.

Dr. Anders disclosed that she has received equipment from LiteCure, grant funding from the Department of Defense, and that she holds advisory board roles with LiteCure and Neurothera. She has also served in leadership roles for the Optical Society and holds intellectual property rights for the Henry M. Jackson Foundation for the Advancement of Military Medicine.

dbrunk@mdedge.com

The Food and Drug Administration has approved Medtronic’s technologically advanced deep brain stimulation (DBS) system designed to more precisely target motor symptoms in Parkinson’s disease, dystonia, or essential tremor.

The SenSight Directional Lead System for DBS therapy combines two recent advancements: sensing capability that allows real-time monitoring of brain signals to optimize settings for stimulation, and a “directional lead” that enables steering of electric current for more precise targeting of stimulation through the electrode.

“Until now, sensing capability and directional leads have not been available in the same DBS system, so we have had to choose one technology or the other, based on the predicted needs of each patient,” neurosurgeon Kelly Foote, MD, who performed the first implant of the SenSight System at University of Florida (UF) Health, said in a news release.

“Now, by coupling this new directional lead with a pulse generator capable of brain sensing, we are excited to be able to offer our patients the synergistic benefits of both technologies,” added Dr. Foote, codirector of the Norman Fixel Institute for Neurological Diseases at UF Health.

Dr. Foote said DBS systems capable of adjusting therapeutic stimulation in response to continuously recorded brain signals may lead to better DBS outcomes with fewer adverse effects.

“Adding a directional lead to such a system will improve our ability to localize abnormal signals and enable us to steer current more effectively to areas in the brain where it is most beneficial,” Dr. Foote said.

“We are excited to see the clinical benefits that the new SenSight directional lead system will provide to patients and physicians in the U.S.,” added Mike Daly, vice president and general manager of brain modulation at Medtronic.

Medtronic’s SenSight directional lead DBS system received CE Mark approval in Europe in March.
 

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

The Food and Drug Administration has approved Medtronic’s technologically advanced deep brain stimulation (DBS) system designed to more precisely target motor symptoms in Parkinson’s disease, dystonia, or essential tremor.

The SenSight Directional Lead System for DBS therapy combines two recent advancements: sensing capability that allows real-time monitoring of brain signals to optimize settings for stimulation, and a “directional lead” that enables steering of electric current for more precise targeting of stimulation through the electrode.

“Until now, sensing capability and directional leads have not been available in the same DBS system, so we have had to choose one technology or the other, based on the predicted needs of each patient,” neurosurgeon Kelly Foote, MD, who performed the first implant of the SenSight System at University of Florida (UF) Health, said in a news release.

“Now, by coupling this new directional lead with a pulse generator capable of brain sensing, we are excited to be able to offer our patients the synergistic benefits of both technologies,” added Dr. Foote, codirector of the Norman Fixel Institute for Neurological Diseases at UF Health.

Dr. Foote said DBS systems capable of adjusting therapeutic stimulation in response to continuously recorded brain signals may lead to better DBS outcomes with fewer adverse effects.

“Adding a directional lead to such a system will improve our ability to localize abnormal signals and enable us to steer current more effectively to areas in the brain where it is most beneficial,” Dr. Foote said.

“We are excited to see the clinical benefits that the new SenSight directional lead system will provide to patients and physicians in the U.S.,” added Mike Daly, vice president and general manager of brain modulation at Medtronic.

Medtronic’s SenSight directional lead DBS system received CE Mark approval in Europe in March.
 

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

The Food and Drug Administration has approved Medtronic’s technologically advanced deep brain stimulation (DBS) system designed to more precisely target motor symptoms in Parkinson’s disease, dystonia, or essential tremor.

The SenSight Directional Lead System for DBS therapy combines two recent advancements: sensing capability that allows real-time monitoring of brain signals to optimize settings for stimulation, and a “directional lead” that enables steering of electric current for more precise targeting of stimulation through the electrode.

“Until now, sensing capability and directional leads have not been available in the same DBS system, so we have had to choose one technology or the other, based on the predicted needs of each patient,” neurosurgeon Kelly Foote, MD, who performed the first implant of the SenSight System at University of Florida (UF) Health, said in a news release.

“Now, by coupling this new directional lead with a pulse generator capable of brain sensing, we are excited to be able to offer our patients the synergistic benefits of both technologies,” added Dr. Foote, codirector of the Norman Fixel Institute for Neurological Diseases at UF Health.

Dr. Foote said DBS systems capable of adjusting therapeutic stimulation in response to continuously recorded brain signals may lead to better DBS outcomes with fewer adverse effects.

“Adding a directional lead to such a system will improve our ability to localize abnormal signals and enable us to steer current more effectively to areas in the brain where it is most beneficial,” Dr. Foote said.

“We are excited to see the clinical benefits that the new SenSight directional lead system will provide to patients and physicians in the U.S.,” added Mike Daly, vice president and general manager of brain modulation at Medtronic.

Medtronic’s SenSight directional lead DBS system received CE Mark approval in Europe in March.
 

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