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Two Parkinson’s Organizations Issue a Total of $5.9M in Research Grants

research grants

The Parkinson’s Foundation and the American Parkinson Disease Association (APDA) have announced a combined $5.9 million in research grants.

For its part, the Foundation is investing $4.2 million in 46 grants to advance promising Parkinson’s disease investigations into new therapies and how the disease works. It also is awarding $8 million to four newly designated Parkinson’s Foundation Research Centers to design and launch studies over the next four years.

“The Parkinson’s Foundation is committed to moving the needle forward in new treatments, medications and better understanding symptoms and disease progression,” John Lehr, the Foundation’s president and CEO, said in a press release. “These research grants are a critical component in our mission to make life better for people with Parkinson’s by improving care and advancing research towards a cure,” he said.

Ranging in length from several months to three years, the awards will go to clinicians and postdoctoral researchers, as well as established scientists. In addition, this grant cycle adds the Melvin Yahr Early Career Award in Movement Disorders Research, created to support post-residency neurologists. The two-year $50,000 grant will support study into brain inflammation in Parkinson’s patients.

“This award is critical for my early independent career development and will help me establish a research program of my own,” said Yulan Xiong, assistant professor at Kansas State University and Stanley Fahn Junior Faculty Award recipient. “The support from the Parkinson’s Foundation will help us better understand a critical PD-related gene. We expect this study will lead to new discoveries in Parkinson’s disease.”

The $8 million in institutional grants — $2 million for each center — will go to Columbia University Irving Medical Center, the University of Florida in collaboration with Emory University, the University of Michigan in collaboration with the University of Texas Southwestern Medical Center, and Yale School of Medicine. These recipients were chosen based on criteria such as research novelty and the ability to address unmet needs in Parkinson’s research.

More information about Parkinson’s Foundation research grants is available here.

At the American Parkinson Disease Association, researchers have been granted $1.7 million for study programs including T-cells and their disease role, genetic factors among Hispanic populations, and the prospects of telehealth psychotherapy in relieving depression.

Awardee highlights include Vikram Khurana, MD, PhD, Brigham and Women’s Hospital in Boston, Massachusetts, winner of the three-year George C. Cotzias Fellowship, the APDA’s most prestigious grant.  He will seek to learn how alpha-synuclein mutation or over-expression affects mRNA regulation in Parkinson’s, which could helpscientists to identify new therapeutic targets and potential gene therapies.

Livia Hecke Morais, PhD, California Institute of Technology, is a post-doctoral fellow who will study microbial brain interaction in Parkinson’s neurodegeneration to understand the relationship between gut bacteria and the disease. This ultimately may lead to the design of new therapies that target gut bacteria for treating Parkinson’s disease.

Research fellow Brian Daniels, PhD, Rutgers University in New Jersey, will investigate RIPK3, a protein associated with Alzheimer’s and amyotrophic lateral sclerosis, as a driver of  inflammation in Parkinson’s disease.

Research fellow Xianjun Dong, PhD, Harvard Medical School in Boston, will explore the possibility of a novel link between genetic susceptibility and Parkinson’s disease.

“We are excited for these researchers to dig deep into their work, and have hope for meaningful outcomes that can make a difference for people living with PD,” the APDA announcement stated.

A list of awardees and descriptions of research projects is available here.

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Have Hope That a New Day Is Coming

new day

It is raining in southern Oregon. Do you know what’s good about so much rain? Things stay green all year long. It might seem depressing, but not today. Today, it’s raining, and though I have Parkinson’s disease, it’s a beautiful day.

The birds are singing. Nothing keeps them from whistling a happy tune. Even when it’s raining, they find something to sing about. 

There are jillions of puddles to jump in, which is exactly what my grandson does. He absolutely loves it. He even gets Grammy to do it sometimes.

Leaves are a bright, spring green. The air smells fresh (for those who still have the gift of smell), and flower roots are refreshed.

When I lived in northern California, there was a time when there was no rain. It was during the big drought. You could only water the landscape once a week. Residents were asked to cut back on laundry and shorten showers. Energy-saving faucets were stocked in hardware stores and signs that said, “If it’s yellow, let it mellow. If it’s brown, flush it down,” were selling like hotcakes.

People were trying to conserve water wherever they could, but despite their efforts, things began to die. Lawns and shrubbery were replaced by species that were less colorful but guaranteed to survive the heat with less water. Kids were disheartened when the summer fun of sprinklers ceased. People obsessed with washing their trucks on a weekly basis were frustrated by the new policies that were set in place.

The drought affected many other things, like river rafting and skiing. We longed for the days when rain would come. We prayed for the days when rain would fall.

Hope renewed

One day, the skies clouded over. There was a hint of hope that turned to joy when drops began to fall. People opened their front doors, walked into the uncommon liquid sunshine, and danced (or at least my neighbor and I did). The rain was a wet welcome to a dry and thirsty area.

Winter can be more than drizzling rain, snow, ice storms, and flooding. It can be a season in our lives when the sun is shining on the rest of the neighborhood, yet dark clouds hover above us, pushing us down, down, down. All that’s left is depression and hopelessness over this stinkin’ disease — and when you have Parkinson’s, the last thing you want (or need) is hopelessness.

“Winter” days for people with Parkinson’s can consist of medications that once worked wonders, but aren’t working so wonderful anymore. Falls may increase in frequency, resulting in frustration over what else Parkinson’s might bring. Your concentration levels may fall, your speech may become more difficult to understand, and you may even feel like you can’t remember anything.

But wait!

It may be raining, but a new day is coming! Maybe you don’t feel like it’s winter. Maybe you feel like you’re struggling through a drought, and the heat is burning up what little hope you have left. But a new day is still coming!

The greatest gift we can give ourselves is the gift of contentment. The gift that enables birds to sing in the rain because they know that whatever the season or weather, they will be taken care of. 

A new day is coming. Hang in there and keep singing.

***

Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

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Depression Is Risk Factor for Impulse Control Disorders in Parkinson’s Patients, Study Finds

depression

Patients with Parkinson’s are at a greater risk of developing impulse control disorders (ICDs) if they are depressed, according to results from an international study.

The findings also revealed that treatment with dopamine agonists increases this susceptibility, and caution is advised when prescribing such therapies to depressed Parkinson’s patients.

The study, “Depression as a risk factor for impulse control disorders in Parkinson’s disease,” was published recently in the journal Annals of Neurology.

Depression and ICDs are two of the most common non-motor symptoms of Parkinson’s disease. However, while depression often precedes the onset of motor problems, ICDs are related to Parkinson’s treatment, especially to dopamine agonists. “This association with [dopamine agonists] makes ICDs a potentially avoidable disorder,” the researchers wrote.

Prior studies have shown that depression and ICDs often coexist in people with Parkinson’s, but were not able to assess whether depression increases the susceptibility for ICDs.

A team of Spanish researchers used data from the Parkinson’s Progression Markers Initiative, a multi-center clinical trial to identify biomarkers of Parkinson’s progression, to address this gap. A total of 354 patients were included, mostly from specialized university hospitals in the U.S. and Europe. None had ICD at baseline, as assessed with the Questionnaire for Impulsive Compulsive Disorders in Parkinson’s Disease.

ICD and medication use were evaluated at follow-up evaluations every three months initially, and every six months after visit four. The researchers also evaluated anxiety with the State-Trait Anxiety Inventory, apathy with the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), and sleep impairments via the REM sleep behavior disorder screening questionnaire.

At baseline, 54.8% of patients were aged between 60 and 75 years and 61.3% were men. The results showed that 68 participants (mean age 60.8 years, 13.3 months since diagnosis) had either depressive symptoms or were diagnosed with depression and taking antidepressants.

The prevalence of depression was higher in women than in men (27.78% vs 15.93%) and depressed patients did not receive dopamine agonists more frequently than non-depressed patients either at baseline or during follow-up.

Also, anxiety and apathy scores were higher in patients with depression (aged 61.6 years, 182 men, 12.7 months since diagnosis).

Over a median follow-up of approximately four years, the patients with depression at baseline showed a nearly two-fold greater risk of developing ICDs, as reflected in an incidence rate of 19.4 cases per 100 patient-years — a measure obtained by multiplying the number of persons at risk over time — compared to 10.3 cases in those without depression.

As shown previously, using dopamine agonists also increased the risk for ICDs. In fact, patients with depression had an ever greater risk of developing ICDs if taking these treatments. Controlling for multiple potential confounding factors — such as age, sex, apathy and anxiety — did not alter these findings.

“Our results show depression acts as a risk factor for the development of ICDs in [Parkinson’s] patients,” the scientists wrote.

“Notably, our results [also] show that the use of [dopamine agonists] in patients with depression is linked to a higher ICD risk,” they added. As such, dopamine should be used with caution in this patient population, the researchers commented.

Importantly, depression should be routinely monitored “to optimize medical decisions regarding the risk of developing ICDs.”

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High Corticosterone Levels a Risk Factor for Parkinson’s, Mouse Study Finds

corticosterone mouse study

High levels of corticosterone — a hormone that regulates energy, immune, and stress responses — is a risk factor for the development and progression of Parkinson’s disease, according to a mouse study.

The study, “Chronic corticosterone aggravates behavioural and neuronal symptomatology in a mouse model of alpha-synuclein pathology,” was published in the journal Neurobiology of Aging.

Parkinson’s disease is a neurodegenerative disorder mainly resulting from the gradual loss of dopaminergic neurons in the substantia nigra, a region of the brain responsible for controlling body movements.

This is a consequence of overproduction and misfolding of the protein alpha-synuclein in neurons, which leads to the formation of small toxic deposits called Lewy bodies that gradually damage and kill nerve cells. Growing evidence has demonstrated that these alpha-synuclein aggregates are associated with Parkinson’s onset and progression.

“Injection of alpha-synuclein preformed fibrils (PFFs) in different brain regions … induces pronounced alpha-synuclein pathology [aggregate] propagation. Interestingly, in these [mouse] models the amygdala is among the brain regions most severely affected by alpha-synuclein pathology [disease],” the researchers wrote.

The amygdala is an area of the brain involved in memory, decision-making, and emotional responses. Several non-motor symptoms in Parkinson’s, including anxiety and depression, have been linked to structural alterations and functional impairments of the amygdala.

“Similarly, chronic stress and glucocorticoid [imbalance] change amygdala physiology [function], and indeed are involved in the development of anxiety and depression,” they wrote.

The group of researchers from the Brain Mind Institute at the École Polytechnique Fédérale de Lausanne in Switzerland set out to investigate if mood/emotional alterations linked to amygdala dysfunction might accelerate the formation and propagation of alpha-synuclein aggregates associated with Parkinson’s in a mouse model of the disease.

To test their hypothesis, they first treated mice with corticosterone, a glucocorticoid that is normally produced in response to stress, to mimic the effects of depression and chronic stress in the amygdala.

Animals were then injected on one side of the brain’s striatum — a region involved in motor and cognitive control — with either alpha-synuclein preformed fibrils to trigger the formation and propagation of alpha-synuclein aggregates across the whole brain, or with a saline solution (vehicle control).

Chronic treatment with corticosterone triggered depression in animals and had a strong effect on their body shape, fat deposition, body weight, and drinking and eating habits. Injection of alpha-synuclein preformed fibrils had no effects on any of these parameters.

Behavioral tests performed one to two months after the injection of alpha-synuclein showed that animals that had been injected with these fibrils displayed mild anxiety, which was reversed by corticosterone treatment.

However, they found that chronic treatment with corticosterone in animals that had been injected with preformed fibrils led to the accumulation of phosphorylated alpha-synuclein in specific regions of the brain, including the entorhinal cortex, a region involved in memory, spatial navigation, and time perception.

Alpha-synuclein phosphorylation is a chemical modification in which a phosphate group is added to the protein. It is known to occur in Parkinson’s disease, and is thought to be a critical step in disease progression, as it enhances alpha-synuclein’s toxicity, possibly by increasing the formation of aggregates.

They also discovered that treatment with corticosterone in mice that had been injected with alpha-synuclein fibrils increased the loss of dopaminergic neurons.

“We report aggravated alpha-synuclein pathology [disease] and neurodegeneration in mice injected with alpha-synuclein [preformed fibrils] in a condition of heightened corticosterone, suggesting heightened glucocorticoid levels as a risk factor for the development of the neuropathological hallmarks of Parkinson’s disease and potential target for treatment,” the researchers wrote.

“Further studies aimed at elucidating the vulnerability factors of specific brain regions to alpha-synuclein pathology, and why at some point resilience fails and neurodegeneration (such as in the substantia nigra) occurs, are needed and will greatly enhance our understanding of the role of alpha-synuclein pathology in the [development] of Parkinson’s disease and synucleinopathies,” they added.

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Low Vitamin D Levels Linked to Added Falls, More Sleep Problems, Depression, Study Shows

low Vitamin D

Low vitamin D levels are associated with a greater tendency for falls, sleep problems, anxiety, and depression in people with Parkinson’s disease, according to a recent study.

The findings, “Relationship between 25‐Hydroxyvitamin D, bone density, and Parkinson’s disease symptoms,” were published in the journal Acta Neurologica Scandinavia.

Vitamin D deficiency and low bone mass are frequently observed in people with Parkinson’s disease (PD). In fact, one particular study found that lack of this vitamin is more common in people with Parkinson’s (55% of patients) than other populations, such as people with Alzheimer’s disease (41% of patients).

But the relationship between vitamin D levels and Parkinson’s has remained controversial. Some studies suggest that taking vitamin D3 — a form of vitamin D used in supplements — can stabilize the disease, while others see no relation with the risk of Parkinson’s.

However, most studies have focused on limited aspects of the disease and did not include important outcomes — notably, non‐motor symptoms.

Vitamin D has a vital role in bone health, since it promotes calcium absorption and bone mineralization, which keeps bones strong and healthy. It also blocks the release of parathyroid hormone (PTH), an hormone that promotes bone tissue reabsorption and bone thinning.

Some studies support that lack of vitamin D results in a greater risk of falls and fractures in Parkinson’s patients, which can increase hospitalization and even fatal disability. Its levels also have been associated with cognition and mood, as well as stomach malfunction, in people with the disease.

While it is possible that deficits in this vitamin impact several symptoms of PD, the connection remains unclear.

To shed light on this relationship, researchers at the Second Affiliated Hospital of Soochow University and Soochow University, in China, set out to determine if vitamin D levels correlated with bone mineral density (BMD) and non‐motor symptoms in Parkinson’s patients.

The team measured blood levels of 25-hydroxyvitamin D, or 25(OH)D — a precursor of the active form of vitamin D and the most accurate indicator of vitamin D levels in the body — and performed extensive clinical evaluations in 182 Parkinson’s patients as well as 185 healthy people (controls).

Participants were recruited from the Second Affiliated Hospital of Soochow University from March 2014 to December 2017.

Bone mineral density — a measure of bone mass and health — was measured at the lumbar spine and the top of the femur (thigh bone) by bone densiometry, which measures bone loss.

The data showed that people with Parkinson’s had significantly lower vitamin D levels in the blood compared with healthy controls — an average of 49.75 versus 43.40 nanomol per liter of 25(OH)D.

In agreement, low levels of vitamin D (below 50 nmol/l) also were more common in Parkinson’s patients (68.68%) than controls (54.05%).

People with lower vitamin D levels were more likely to fall and experience sleep problems, including difficulty in falling asleep (insomnia). They also had significantly more depression and anxiety.

Mean bone densities in both the spine and femur were lower in PD patients, however no correlation was seen between the levels of BMD and vitamin D.

“Together, these results indicate that vitamin D deficiency may play a role in PD pathogenesis [disease manifestations], while vitamin D supplementation may be used to treat the non‐motor symptoms of PD,” the researchers  said.

“As various non-motor symptoms place a burden on individuals with Parkinson’s disease and their caregivers, vitamin D might be a potential add-on therapy for improving these neglected symptoms,” study’s senior author Chun Feng Liu, MD, PhD, said in a press release.

However, the researchers stressed that future studies with a larger sample size are necessary to clarify the role of vitamin D in Parkinson’s disease.

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Women with Depression and Anxiety Are Largest Parkinson’s Group with Fibromyalgia, Study Finds

Parkinson's and fibromyalgia

A distinct population of people are diagnosed with both Parkinson’s disease and fibromyalgia, a study in Israel found, noting they tend to be women with mental health issues, such as depression and anxiety, who rely on painkillers more than other Parkinson’s patients.

The study, “Fibromyalgia-Like Syndrome Associated with Parkinson’s Disease—A Cohort Study,” was published in the Journal of Clinical Medicine.

Fibromyalgia is a chronic condition characterized by widespread pain in various parts of the body. Parkinson’s and fibromyalgia share clinical features like muscle stiffness, unusual pelvic and rectal discomfort, poor sleep, fatigue, and depression. Nonetheless, only one case study to date has detailed a patient with both diseases, the researchers said.

“Since PD [Parkinson’s disease] and FM [fibromyalgia] are two relatively common disorders, it is not uncommon for a neurologist, rheumatologist, or a pain specialist to encounter a patient suffering from both illnesses,” they added.

Investigators at the Ben Gurion University sought to retrospectively characterize this specific group of patients, looking at their demographics, comorbidities, and medication use.

The team searched the Clalit Health Services database between the years 2000 and 2015 for people diagnosed with Parkinson’s and fibromyalgia. Researchers identified Parkinson’s patients through the application of a medication tracer algorithm, and those with fibromyalgia based on medical records.

During this 15-year period, 2,606 people (1,220 women and 1,386 men; mean age 67.9) were diagnosed with Parkinson’s and 60 (2.3%) of them also had fibromyalgia (a fibromyalgia-like syndrome associated with Parkinson’s disease, referred to as FLISPAD).

The majority of those with both the neurodegenerative and rheumatic disorders were women (88.3%) diagnosed at a mean age of 63.95 for Parkinson’s, while their age at fibromyalgia diagnosis varied from 51.68 to 76.22 years. A majority — 77% — also received a fibromyalgia diagnosis after that of Parkinson’s disease.

This particular patient population also had a higher prevalence of depression, anxiety, dementia, hypertension, and heart failure.

Compared to those with Parkinson’s, patients with both conditions used different analgesics (painkillers) at higher rates as well as more antidepressants.

“This FLISPAD subgroup of patients are mostly female, younger at PD diagnosis with a higher rate of cigarette smoking, anxiety, and depression,” the researchers wrote. And they “consume more analgesic drugs, both over-the-counter (OTC) and prescription medications, including opioids.”

A diagnosis of depression or use of antidepressants tended to come a mean 3.5 years before a fibromyalgia diagnosis.

Results also showed that Parkinson’s and fibromyalgia patients purchased 21.3% more anti-parkinsonian medications than those who did not have fibromyalgia. Although not significant, this finding achieved borderline statistical significance.

“These patients present a challenge for physicians as they use more analgesics, psychotropic medications, and tend to also use more APDs [anti-parkinsonian drugs] over time. More research is needed to determine the etiology and determinants of this syndrome, the needs of patients and course of treatment, both for PD [Parkinson’s disease] and FM [fibromyalgia] symptoms,” the researchers concluded.

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Resistance Training Reduces Depressive Symptoms in Older PD Patients, Trial Shows

Resistance training

Twenty weeks of resistance training significantly decreases depression symptoms and improves quality of life in older people with Parkinson’s disease (PD), a study has found.

The training, consisting of exercises involving the arms and legs and simulating daily activity movements, also improved patients’ flexibility, endurance, and walking performance.

Based on the promising results, researchers are calling for resistance training to be included in exercise programs for patients with Parkinson’s disease.

Their study, “Resistance training reduces depressive symptoms in elderly people with parkinson disease: A controlled randomized study,” was published in the Scandinavian Journal of Medicine and Science in Sports.

Loss of muscle strength and function predisposes Parkinson’s patients to sedentary behavior and social isolation, with consequent increase in depressive symptoms, affecting up to 40% of patients.

But studies suggest that those who have a more active lifestyle and exercise are less prone to depression.

Some researchers contend that exercise works at least as well as antidepressants. The effect of exercise as natural antidepressant is thought to be mediated either by stimulating the growth of new nerve cells — as antidepressant medications might — or releasing substances from muscles and fat cells (adipocytes) that can travel to the brain and work as antidepressants.

Up to now, known effective physical therapies against depression in Parkinson’s are based mostly on  aerobic exercises.

Here, Brazilian researchers conducted a trial to evaluate the benefits of another exercise modality — resistance training — in reducing depression and improving quality of life in elderly patients with PD.

Considering its potential physical benefits, researchers investigated how much this type of training improved patients’ movement and resistance capacity as well. The trial was sponsored by Pará State University, in Brazil.

Resistance training is a form of exercise designed to improve muscular fitness by exercising a muscle or a group of muscles against any object that poses an external resistance. This causes muscles to contract, which can help improve strength, power, muscle growth, and endurance.

The trial involved 33 patients, age 60 or older, who were randomly assigned to resistance training (17 patients) or a control group (16 patients) for 20 weeks. All were on stable medication and had Parkinson’s stage 1-3 on the Hoehn and Yahr scale.

Those in the resistance training group spent the first two weeks getting used to the exercises, under supervision. After that, they started having training sessions twice a week, on non-consecutive days.

Each session (30–40 minutes each) consisted of two series of of 8–12 repetitions of these exercises: bench press, deadlift, unilateral rowing, standing calf raise and abdominal reverse crunch. Such exercises involve the major muscle groups in the arms and legs and mimic the basic movements of daily activities.

Training loads were increased when the patient had a high performance, with full range of motion.

Unlike the control group, at the end of the 20 weeks, patients performing resistance training had fewer depressive symptoms. Clinician-rated HAM-D17 scores dropped from 17.9 to 10.3.

Patients in this group also reported improvements in their quality of life (as measured by the Parkinson’s disease Questionnaire, PDQ-39) and had better UPDRS scores, which rate Parkinson’s motor and non-motor symptoms.

Concerning motor capacity, resistance training also improved patients’ physical performance as seen in several tests — Timed Up and Go (pre-training, 33.2 seconds versus post training, 26.4 seconds), flexibility on the sit and reach test (pre, 20.7 cm versus post, 28.8 cm), aerobic endurance measured by the two-minute step test (pre, 79.2 steps versus post, 99.1 steps) and maximum walking speed (pre, 1 meter per second versus post, 1.3 meters per second).

In contrast, no significant changes were seen in the control group, either regarding depressive symptoms, quality of life, or motor skills.

“In addition to improving functional capacity and quality of life, resistance training reduces depressive symptoms of elderly with Parkinson’s disease,” the researchers said.

“To our knowledge, the present study is the first to show that 20 weeks of isolated resistance training reduced depressive symptoms in elderly people presenting PD. We suggest that resistance training should be a central component of exercise programs for patients with Parkinson’s disease,” they concluded.

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Inflammatory Molecules in Blood May Help Predict Parkinson’s Progression, Study Suggests

machine learning, cytokines

Inflammatory molecules called cytokines may be a peripheral biomarker of Parkinson’s progression, especially of its characteristic changes in motor abilities, according to new research using machine learning.

The study, “Parkinson’s progression prediction using machine learning and serum cytokines,” appeared in the journal npj Parkinson’s Disease.

Besides altered immune responses and distinct populations of immune cells, increased levels of cytokines — small proteins secreted by cells of the immune system — may link inflammation with Parkinson’s. This has been seen in asymptomatic carriers of the G2019S mutation in the LRRK2 gene, which accounts for 1–5% of all Parkinson’s cases. Still, the extent to which peripheral cytokines may trigger the disease remains unclear.

Increasing evidence suggests that Parkinson’s may start in the periphery (for example, in the gut), possibly enabling the identification of markers of disease progression that could improve outcomes for patients and lead to better trial design.

Researchers at The University of Sydney, Australia, used machine learning to further assess the correlation between peripheral inflammatory cytokines and Parkinson’s symptoms. They analyzed serum samples from 160 patients (mean age 68–69, ages 57–58 at diagnosis), 80 of whom (40 men) had the G2019S mutation and 80 who did not (54 men), all followed within the Michael J Fox Foundation Parkinson’s Progression Markers Initiative. They then used machine learning models to predict clinical outcomes at two years.

Comparing the two groups, patients who carried the G2019S mutation had milder motor disease and less severe hyposmia — a reduced sense of smell — as assessed with the Unified Parkinson’s Disease Rating Scale part 3 (UPDRS-III) and the University of Pennsylvania smell identification test. At baseline (study start), mutation carriers also had higher levels of the cytokines PDGF and MCP1 than those in the group of idiopathic (of unknown cause) Parkinson’s disease.

One year later, the scientists assessed blood serum samples from 126 of these patients. Results revealed that two cytokines, GCSF and interleukin (IL)-5, had the greatest variation. However, only the levels of one cytokine, IL-1RA, differed between the two groups.

Clinically, the patients showed more severe motor symptoms and depression, which were associated with a significantly decreased (worse) score in the Schwab and England activities of daily living (ADL) scale.

A subsequent analysis showed that, among a subset of 76 patients, higher baseline levels of 14 cytokines correlated with greater (worse) findings on the geriatric depression scale over two years. A similar link was found between seven cytokines and motor function. IL-5 and GCSF were among the cytokines whose levels correlated with both scales.

Using machine learning, researchers observed that two cytokines, MIP1 alpha and MCP1, made the biggest peripheral contribution to predicting motor symptom severity using the Hoehn and Yahr and UPDRS III scales, respectively.

As such, higher levels of these molecules were associated with faster motor deterioration.

In turn, the cytokines IL-6 and IL-4 were the primary contributors to predicting geriatric depression. All top cytokine contributors were also good predictors of the Schwab and England ADL scale scores.

Using cytokines improved predictions by 20% over clinical data alone. As for other analyzed variables, age and gender were among the top 10 contributors to predicting ADL and UPDRS-III scores, respectively.

“These results provide information on the longitudinal assessment of peripheral inflammatory cytokines in [Parkinson’s] and give evidence that peripheral cytokines may have utility for aiding prediction of [Parkinson’s] progression,” the scientists wrote.

Future studies should use a larger and more diverse group of patients, and assess the potential impact of medications on both clinical outcomes and cytokines levels, the researchers added.

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Depression and Psychosis Are Markers of More Severe Disease, Database Study Says

mental illness and Parkinson's

Mental illness in people with Parkinson’s disease, more frequently found in female and older patients, appears to associate with more severe disease, a new study reports.

Titled, “Comorbid Depression and Psychosis in Parkinson’s Disease: A Report of 62,783 Hospitalizations in the United States,” the study was published in the journal Cureus.

Although Parkinson’s disease is best known for its motor symptoms, non-motor symptoms can play an impactful role too. Depression and psychosis (difficulty discerning what’s real and what isn’t) are both psychiatric disturbances known to occur in Parkinson’s patients, and these conditions can, understandably, seriously impact their quality of life.

Researchers across the U.S. set out to examine the interplay between these mental illnesses in Parkinson’s and disease severity, patient demographics, and hospital outcomes.

They analyzed data from the Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample (NIS) covering 2010–14; this included information on 62,783 people with Parkinson’s, of whom 11,358 (18.1%) were diagnosed with depression and 2,475 (3.9%) experienced psychosis.

Both mental health conditions were significantly more common in female patients; women made up 37.2% of the total population, but 44.9% of those with depression and 41.8% of those with psychosis.

Depression was more common among white patients (84.9% with depression were white, compared to 80.6% white in the total population), whereas a disproportionate percentage of people with psychosis were black (8.7% vs. 6.5% of total population) and were in the lowest quartile of household income (28.6% vs. 22.4% in the total population).

Older patients were also more likely to experience mental illness, with those older than 80 years at a 5.3-fold greater risk than patients in their 40s and 50s.

Having psychosis was associated with more severe disease: 78.8% of Parkinson’s patients with psychosis had moderate or severe disease compared to 66.2% of the total population, meaning patients with psychosis were 1.38 times more likely to have more severe disease. In those with depression, 67.9% had moderate or severe disease, a similar rate as seen in the total population.

Additionally, around a quarter of the total population received deep brain stimulation (DBS) as part of their treatment. A similar proportion of patients with depression were given DBS, but only 3.9% of patients with psychosis did.

Patients with psychosis also tended to have longer average hospital stays (7.3 vs. 4.1 days in the psychosis and total cohorts, respectively), but, interestingly, lower average total hospital charges ($31,240 vs. $39,688 in the total cohort). Both average length of hospital stay and average costs were similar for the total population and those with depression.

These results are all only associations; the study was not designed to find cause-and-effect relationships, and regardless, such relationships are likely affected by the combination of many factors. More research will be needed to better understand the interplay between these factors, but this work does highlight the impact of mental health in Parkinson’s disease.

“The results of our study suggest that healthcare providers should actively screen for psychiatric comorbidities like depression and psychosis in patients with PD [Parkinson’s disease],” the researchers concluded, adding, “[p]sychiatric comorbidities in PD should be considered an integral part of the disease, and a multidisciplinary approach to managing this disease is crucial to improve the overall outcome and the health-related quality of life of PD patients.”

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Yoga Decreases Anxiety and Depression More Than Resistance Training, Study Finds

yoga, mindfulness

Mindfulness yoga seems to be better than conventional exercise at alleviating depression and anxiety in people with Parkinson’s disease, according to a recent study.

The study with that finding, which was published in the journal JAMA Neurology, is titled, “Effects of Mindfulness Yoga vs Stretching and Resistance Training Exercises on Anxiety and Depression for People With Parkinson Disease.”

It’s well-established that exercising regularly has a multitude of health benefits for people with Parkinson’s. Exercising also is known to have psychological benefits, particularly when a mindfulness component is incorporated.

In the study, the mental health effects of mindfulness yoga and more conventional stretching and resistance training exercises were compared head-to-head.

Researchers recruited 138 adults with Parkinson’s disease at four community rehabilitation centers in Hong Kong, between Dec. 1, 2016, and May 31, 2017. All patients had a clinical diagnosis of idiopathic (of unknown cause) Parkinson’s disease and were able to stand unaided and walk with or without an assistive device.

Individuals were assigned randomly to participate in mindfulness yoga (71 people) or resistance exercises (67 people). A slim majority (52.9%) of the participants were female, the average participant age was 63.6 years, and both groups were similar in terms of demographics, etc., although slightly more in the yoga group were less educated and lived at home.

Both interventions consisted of weekly classes offered once per week, with participants encouraged to practice at home, too. Average attendance rates for the eight-week intervention were 6.1 classes for both groups, and about three-quarters of participants in both groups reported actually practicing at home. Over the course of the study, some participants dropped out for reasons that included disinterest and scheduling conflicts; dropout rates were comparable between the two groups.

Before and after the intervention, depression and anxiety were measured using the Hospital Anxiety and Depression Scale.

In the yoga group, anxiety scores decreased from 6.32 before the intervention to 3.04 afterward; this decrease was significantly larger than the decrease seen in the resistance exercise group (5.66 to 4.95). Similarly, depression scores in the yoga group decreased significantly more than those in the conventional exercise group (6.69 to 3.53 vs. 6.16 to 6.00).

Motor skills also were assessed (via the MDS-UPDRS), and similar improvements were observed in both groups: a decrease from 34.90 to 22.41 in the yoga group, and from 31.64 to 23.25 in the resistance exercise group. Of note, higher MDS-UPDRS scores reflect worse motor capacity.

The data suggest that, while both interventions provide comparable physical benefits, the mental health benefits of mindfulness yoga are superior to those of stretching and resistance training exercises.

A few instances of mild knee pain in both groups were the only adverse side effects reported; these were resolved without medical intervention.

“These findings suggest that mindfulness yoga is an effective treatment option for patients with [Parkinson’s disease] to manage stress and symptoms,” the researchers concluded in their paper, adding that “[f]uture rehabilitation programs could consider integrating mindfulness skills into physical therapy to enhance the holistic well-being of people with neurodegenerative conditions.”

Limitations of this study include the small sample size and the fact that participants were fully aware of which group they were put into, so it’s possible that participant bias may have influenced the results.

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