Genetic Differences Behind Brain Structures Likely Influence Risk of Neurological Conditions, Study Says

genetic differences, Parkinson's

Genetic differences influence the physical properties of the brain’s cerebral cortex and likely play a key role in cognition and risk of neurological conditions, including Parkinson’s disease, a new study has found.

Titled “The genetic architecture of the human cerebral cortex,” the study was published in the journal Science.

The cerebral cortex, the highly-folded outer layer of the brain, is a region crucial for processing information, memory, thinking, and attention. There are differences between individuals in the physical properties of the cerebral cortex, such as its thickness and surface area (essentially, how densely folded the tissue is). Some of these differences have previously been linked to conditions such as attention deficit hyperactivity disorder (ADHD) and schizophrenia, as well as to cognition in general.

Genetics play an important role in guiding the development of the brain. But, to date, most studies on the genetics underpinning brain development have been done in mice, making it difficult to draw conclusions about human biology.

“The genetic basis for a mouse is very different than the genetic basis for humans,” Jason Stein, PhD, professor at the University of North Carolina School of Medicine and co-author of the new study, said in a press release.

In the study, researchers collected magnetic resonance imaging (MRI) scans, as well as genetic data, of 51,665 people.

“This study was only possible due to a huge scientific collaboration of more than 60 sites involved in MRI scanning and genotyping participants,” Stein said.

By combining the MRI and genotype data, the researchers identified 306 regions in the genome where variations in the DNA code were significantly associated with differences in the thickness and/or surface area of the cerebral cortex. Of these, 299 regions had data available for replication and 199 regions remained significant after several statistical analyses.

Collectively, genetic variations accounted for 34% of the variation in surface area and 26% of the variation in thickness (the rest of the variation would be determined by other factors, such as the environment in which a person lives).

Subsequent analysis of the regions in question revealed that genes associated with surface area were generally active early on in fetal development. In contrast, genes involved in regulating thickness were more active during adulthood.

Interestingly, many of these variations were in parts of the genome that don’t code for proteins (non-coding regions). While historical biological understanding was that genes encode proteins, which then carry out functions, this study adds to an accumulating wealth of evidence showing that non-coding parts of the genome also have important functions.

The researchers noted significant associations between cerebral cortex surface area and both general cognitive functioning and educational attainment. In other words, individuals with higher cortex surface areas were more likely to have greater cognition and to have had more education. The statistical analysis suggested that this was a bidirectional causation relationship. In other words, there was evidence to suggest that higher brain surface area caused people to have better cognition, and also that having higher cognition caused brain surface area to increase.

Significant associations were found between high cortex surface area and genetic risk for Parkinson’s disease, but there was no evidence of a cause-and-effect relationship.

Lower cerebral cortex surface area was significantly linked with genetic risk of insomnia, ADHD, and depression.

Overall, the study provides new insight into how genetic variations help to control the development of the brain.

“This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning,” the researchers said.

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‘Inappropriate’ Antipsychotics to Treat Depression in Elderly Parkinson’s Patients Linked to Pneumonia Risk


Inappropriate antipsychotic medications — those approved for ills like schizophrenia but used to treat depression — given to elderly people with Parkinson’s disease increase their risk of pneumonia, a study suggests.

The study, “Risk of pneumonia associated with atypical antipsychotic use in nursing home residents with Parkinson’s disease,” was published in the Journal of Psychiatric Research.

Certain antipsychotic medications can be prescribed to help handle some of the behavioral problems evident in Parkinson’s disease (PD). But use of antipsychotics in these patients must be done cautiously, since many affect dopamine signaling — which is dysregulated in PD — and can aggravate other disease symptoms.

According to the 2019 American Geriatrics Society (AGS) Beers criteria, atypical antipsychotics are not appropriate for Parkinson’s patients, with exceptions being Nuplazid (pimavanserin), clozapine (brand names, Clozaril and FazaClo), and quetiapine (Seroquel). (Nuplazid, an oral Parkinson’s psychosis treatment that does not impact motor abilities, was approved in 2016, outside the years of this study.)

Atypical antipsychotics are considered inappropriate due to the risk of worsening Parkinson symptoms, like voluntary movements in general and swallowing abilities in particular.

Researchers in the U.S. investigated the link between inappropriate antipsychotic use and pneumonia, which can be a serious complication when swallowing or breathing are impaired.

Using Medicare data, they identified 16,161 nursing home residents diagnosed with Parkinson’s and depression (mean age, 82; two-thirds female), who were treated with antipsychotic medications between 2007 and 2010. Over a third of these individuals (37.62%; 6,126 people) were given an inappropriate antipsychotic, while the remainder were prescribed an appropriate one, with the most common being quetiapine.

Among these elderly patients, rates of dysphagia (difficulty swallowing), dementia, and levodopa use were similar between groups treated with appropriate and inappropriate antipsychotics.

Rates of pneumonia were significantly higher in patients prescribed inappropriate antipsychotics, 18.78% vs. 16.35%, than in those given appropriate ones over a six-month follow-up. Inappropriate antipsychotic use was also associated with a 20% greater chance of pneumonia, statistical analyses found; this finding was validated through sensitivity analyses that work against uncertainty in given sets of assumption.

Researchers also noted that rates of stopping antipsychotics were higher among those on inappropriate medications (21.17% vs. 15.22%).

“The risk of pneumonia was significantly higher for inappropriate AAP [antipsychotic] users in comparison to the appropriate AAP users,” the researchers wrote.

“The study findings suggest that selection of appropriate antipsychotics in PD is critical to prevent serious adverse events related to antipsychotic use in PD, given that pneumonia is one of the most common causes of mortality in PD patients. Further research is needed to evaluate the risk of pneumonia in PD patients using newer antipsychotic medications,” they concluded.

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Finding Wisdom from an Unexpected Source


“I looked ahead and could not see a future I wanted to live.” 

These were the words of Chris Norton, co-author of “The Seven Longest Yards,” as he lay in his hospital bed and the truth of his condition sank deep into his soul. 

Quadriplegic. The day before, he was playing football for Luther College in Decorah, Iowa. Now he was trying to grapple with the fact that his chances of ever moving anything below his neck were 3 percent.

Not very encouraging.

Chris Norton’s story isn’t about Parkinson’s disease (PD). But those of us with PD would do well to heed his wisdom.

What some called a tragedy became multiple blessings for Chris and his wife, Emily. But those blessings came at a price. Their perseverance, faith, and steadfastness were tested every step of the way. And step by what felt like impossible step, they continued to move forward.

Imagine working out day after day, hoping to be in that 3 percent. Imagine going to the gym every day knowing there’s a 97 percent chance you will never get better.

Sound vaguely familiar in a different sort of scenario?

Those of us with Parkinson’s know we are not going to heal ourselves with exercise. We are trying to maintain our current status on the PD scale. At best, we hope to improve to some degree. It is that “some” that keeps us going. 

A big difference between Chris and many people with a chronic disease whom I have met is attitude. Our attitude can determine how well we will live with Parkinson’s. 

The power of attitude hit Chris strong. In his book, he writes that he wondered why he was feeling sorry for himself when he could be doing something to get better.

“… Everything changed when I switched my focus to what I could do. … I realized that my attitude had the power to change my reality. … I didn’t dwell on the laundry list of things I couldn’t do. I focused on what I could do.

There were dark days for Chris, especially when Emily struggled with depression. Her story within this story is worth the read for anyone struggling with mental illness.

If you long for an encouraging word by someone who can relate — even if on a different level — the Nortons’ book won’t be a disappointing read.

As Chris writes: “Your circumstances do not determine your future. Your responses to your circumstances do. … Don’t focus on what you can’t do. Focus on what you can do.”

Great words for all of us.


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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Nuplazid Eases Depression in Parkinson’s Patients, Phase 2 Trial Shows


Treatment with Nuplazid (pimavanserin), approved in the U.S. for treating hallucinations and delusions associated with Parkinson’s psychosis, eased depression and sleep problems in patients with Parkinson’s, according to results from a Phase 2 clinical trial.

The research, “Open-Label Study of Pimavanserin Patients With Comorbid Parkinson’s Disease and Depression,” was presented at the 2019 International Congress of Parkinson’s Disease and Movement Disorders in Nice, France.

Depression is one of the most frequent non-motor symptoms of Parkinson’s. While its severity and duration typically increase with disease progression, easing depression has been linked with greater quality of life and less disability.

An eight-week, open-label, study (NCT03482882) assessed Acadia Pharmaceuticals’ Nuplazid either as a stand-alone therapy, or as an add-on to a selective serotonin reuptake inhibitor (SSRI, a type of antidepressant) or a selective norepinephrine reuptake inhibitor (SNRI) for Parkinson’s patients with depressive symptoms. The 47 participants, all 50 or older, received two 17 mg oral tablets per day of Nuplazid.

Nuplazid is a selective serotonin inverse agonist that targets serotonin receptors called 5HT2A receptors. Inverse agonists bind to the same receptors as agonists, but induce the opposite pharmacological response. Serotonin receptors are found throughout the nervous system. Specifically, 5HT2A has been associated with mental disorders such as depression and epilepsy.

The results found significant benefits as early as week 2 assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17) — the study’s primary goal. At week 8, 60% of the participants showed an improvement of at least 50% on the HAMD-17 score, with 44.4% of patients reaching remission (HAMD-17 score up to 7).

The study also showed improvements on the Clinical Global Impression-Severity scale (a measure of disease severity) and the Clinical Global Impression-Improvement — a 0.5 lower score from week 2 to week 8, as rated by clinicians.

Sleep measures, namely the SCOPA-nighttime sleep and SCOPA-daytime sleepiness scales, also revealed benefits from week 4 to week 8. Likewise, the SCOPA-Global Sleep Quality scale showed significant improvements comparing week 8 to baseline.

“Results of this open-label study suggest that pimavanserin may be a potential treatment to be further investigated for depression associated with Parkinson’s,” Gus Alva, MD, a co-author of the study, and founder and medical director of ATP Clinical Research, said in a press release.

Treatment with Nuplazid was well-tolerated, with treatment emergent adverse events (TEAE) being in line with other studies of this therapy. Reported TEAEs included falls (8.5%), nausea (6.4%), diarrhea (4.3%), edema, or swelling (4.3%), skin abrasion (4.3%), and urinary tract infection (4%).

“Pimavanserin [Nuplazid] as adjunctive or monotherapy is associated with early sustained improvement of depressive symptoms in patients with [Parkinson’s] and is well tolerated,” the scientists wrote.

“We are pleased with the exploratory study results which show a positive treatment effect with pimavanserin [Nuplazid] for depression in patients with Parkinson’s,” said Serge Stankovic, MD, Acadia’s president.

Stankovic commented that the results are consistent with those of the 10-week CLARITY Phase 2 study (NCT03018340). Using Nuplazid as an add-on led to improved HAMD-17 scores, while also easing disability and sleepiness,  and improving sexual function in patients with major depressive disorder with inadequate response to standard SSRI/SNRI treatments.

Nuplazid is currently being tested in two six-week Phase 3 studies named CLARITY-2 (NCT03968159) and CLARITY-3 (NCT03999918), each with approximately 280 patients. Patients who complete these trials will be able to participate in a 52-week open-label extension study (NCT04000009) to assess long-term safety and tolerability. These three studies are currently enrolling. (For more information, follow the links on the NCT identifiers.)

“We are committed to continued research for pimavanserin [Nuplazis] to address unmet medical needs in central nervous system disorders, including our ongoing Phase 3 clinical program in major depressive disorder,” Stankovic said.

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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


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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