Riding the road less travelled: Colwood resident raising funds, awareness of Parkinson’s disease

August 11, 2018  Kendra Wong

Alf Todd to rise 200 kilometres from Victoria to Sproat Lake in one day

Colwood residents Alf Todd and his wife, Patty. Todd was diagnosed with Parkinson’s disease 11 years ago. On Saturday, Aug. 11, Todd will be cycling 200 kilometres from Victoria to Sproat Lake to raise money for Parkinson’s programs at Headway Victoria Epilepsy and Parkinson’s Centre. (Contributed photo)

When Alf Todd straps on his helmet and jumps onto his bike he feels like a new man.

Despite living with Parkinson’s disease for the last decade, when he starts pedalling the stiffness and rigidity of his body fades away. He forgets about the fact that he lost his sense of smell years ago and focuses on the journey ahead.

“There’s times in the day where I can barely walk, but once I get on the bike I don’t have Parkinson’s. It’s a different signal from the brain to the extremities. It’s complicated and I don’t fully understand it,” laughed the now 66-year-old Colwood resident, who is raising awareness of the disease this weekend.

Todd was originally diagnosed with Parkinson’s disease, a progressive nervous system disorder that affects movement, 11 years ago. Symptoms, such as tremors, start gradually and can result in stiffness and slowing of overall movement. There is no cure.

“I knew there were issues. I knew something was going on, I didn’t know what,” said Todd about being diagnosed.

“After my doctor suggested it could be Parkinson’s, I went home and punched in Parkinson’s symptoms on the computer and there was a check list. There was no question in my mind.”

Despite the diagnosis, Todd remained positive and refused to let it take over his life. He still had things he wanted to accomplish, and wanted to be physically able to play with his five grandchildren.

Then he hopped on his bike again. It was slow going at first, but now, Todd rides his bike almost everywhere he goes – an activity that helps his Parkinson’s. In recent years, Todd has combined his passion for cycling with finding a cure for the disease.

Roughly six years ago, Todd and his daughter organized a long-distance ride from Victoria to San Francisco in which 16 riders raised close to $30,000.

Last June he also organized a ride from Port Hardy to Victoria with 15 riders – six of whom suffer from the disease and raised roughly $28,000. Both fundraisers were in support of Parkinson’s research.

Fast forward a few years and this weekend, Todd will be embarking on another challenging ride – cycling 200 kilometres from Victoria to Sproat Lake in one day to raise money for Parkinson’s programs at Headway Victoria Epilepsy and Parkinson’s Centre on Oak Bay Avenue.

Overall, he hopes to bring awareness to the disease.

“Cancer gets lots of attention and breast cancer and that’s fantastic they need it, but there’s a lot of other places too that need research, ALS, MS, Parkinson’s, there’s so much,” Todd said.

“I realize you can’t give to everything, but when we do a fundraiser and make $10,000 or $20,000, it’s only a drop in the bucket. But some day the bucket will fill.”

In addition to the ride, Todd has also set up an online fundraising campaign that has raised over half of its $3,000 goal.

The bike ride takes place on Saturday, Aug. 11, where Todd will depart at 6 a.m. from 3118 Antrobus Cresc before riding to Sproat Lake.

To donate to the cause, visit gofundme.com and search Support Alf’s ride for Parkinson’s. 

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https://www.saanichnews.com/community/riding-the-road-less-travelled-colwood-resident-raising-funds-awareness-of-parkinsons-disease/

Elderly Dialysis Patients Have a Higher Risk of Dementia

August 10, 2018
Source: Johns Hopkins University.

A new study reports older adults who receive dialysis treatment for kidney disease have an increased risk of being diagnosed with dementia.

Studies over the past two decades have found evidence that as kidney function declines, cognitive functions are apt to decline as well. NeuroscienceNews.com image is credited to Anna Frodesiak.

Older kidney disease patients who are sick enough to require the blood-filtering treatment known as dialysis are at high risk of dementia, including Alzheimer’s disease, according to a study led by scientists at Johns Hopkins Bloomberg School of Public Health.

The study, published Aug. 9 in the Clinical Journal of the American Society for Nephrology, found evidence that older kidney disease patients had a substantially higher risk of being diagnosed with dementia than community-dwelling older adults.

“The dementia risk in this population seems to be much higher than what we see among healthy community-dwelling older adults,” says study lead author Mara McAdams-DeMarco, assistant professor of epidemiology at the Bloomberg School.

To McAdams-DeMarco and her colleagues, the findings suggest that doctors should be doing more to monitor, and if possible to slow or prevent, cognitive decline among older dialysis patients. “The high incidence of dementia seems to be overlooked in this population,” she says.

Cognitive decline and dementia, including Alzheimer’s disease, are principally age-related and relatively common in the elderly. However, research suggests that kidney disease appears to worsen the problem. Studies over the past two decades have found evidence that as kidney function declines, cognitive functions are apt to decline as well. One recent study in dialysis patients found that this kidney-related cognitive decline was particularly noticeable for executive functions such as attention, impulse control and working memory.

The precise biological mechanism linking kidney disease to brain problems isn’t yet clear, but kidney disease has itself been linked to poor blood flow in the brain, so researchers suspect that as a key factor.

To get a better understanding of the dementia problem among elderly patients with advanced kidney disease, McAdams-DeMarco and colleagues examined a large national kidney disease registry, focusing on 356,668 Medicare patients older than 66 years who had initiated dialysis due to end-stage kidney disease during 2001-2013.

Their analysis was aimed mainly at estimating the risk of a dementia diagnosis within a given period after initiating dialysis. For the female patients in this group, the estimated risk was 4.6 percent for a dementia diagnosis within a year, 16 percent within 5 years, and 22 percent–a nearly one in four chance–within 10 years. For males, the corresponding figures were slightly lower at 3.7, 13 and 19 percent.

Alzheimer’s disease represented a significant proportion of dementia diagnoses: The one-year risk of this form of dementia was 0.6 percent for women and 0.4 percent for men.

The study was not designed to compare dialysis patients directly to healthy people of the same age; even so, the dementia risk among these patients was considerably higher than what would be expected in this age group. For example, a well-known prior study following residents of a Massachusetts town found that community-dwelling 65-year-olds had only a 1.0 to 1.5 percent incidence of dementia within 10 years, while for 75-year-olds the incidence was only about 7.5 percent. By contrast, in this study the researchers determined that the 10-year risk of dementia after starting dialysis was 19 percent for patients in the sample aged 66 to 70, and 28 percent among 76- to 80-year-olds.

Even the Alzheimer’s disease risk among the dialysis patients seemed higher than normal–for example, 4.3 percent of the 66-70-year-olds were diagnosed with the disease within 10 years of starting dialysis, compared to a 10-year incidence of less than 1 percent among 65-year-olds in the Massachusetts study. That suggests that older patients with end-stage kidney disease may even be vulnerable to Alzheimer’s disease.

McAdams-DeMarco and colleagues also found that older dialysis patients with a dementia diagnosis were about twice as likely to die at any time in the study period, compared to older dialysis patients without a dementia diagnosis.

As stark as these findings are, they may understate the problem. “We know from other studies that only about half of patients with dementia receive a diagnosis, so the figures in this study could be seen as a lower limit,” McAdams-DeMarco says.

She and her colleagues suggest that more in-depth studies need to be done to gauge the true extent of the dementia problem among older end-stage kidney disease patients. “Patients starting dialysis generally meet with health care providers a few times per week, so in principle there is ample opportunity to do at least brief cognitive screening,” she says.

She also recommends more studies of potential measures to prevent dementia among these vulnerable patients. “We’re currently setting up a large clinical trial to identify appropriate interventions to preserve cognitive function in these patients,” McAdams-DeMarco says.

About this neuroscience research article

Funding: Funding was provided by the National Institutes of Health (R01AG042504, K24DK101828, R01AG055781, R01DK114074, K01AG043501, and K01AG050699).

Source: Barbara Benham – Johns Hopkins University

Publisher: Organized by NeuroscienceNews.com.

Image Source: NeuroscienceNews.com image is credited to Anna Frodesiak and is licensed Creative Commons CC0 1.0 Universal Public Domain Dedication.

Original Research: Abstract for “Dementia, Alzheimer’s Disease, and Mortality after Hemodialysis Initiation” by Mara McAdams-DeMarco, Matthew Daubresse, Sunjae Bae, Alden Gross, Michelle Carlson and Dorry Segev in Clinical Journal of the American Society of Nephrology. Published August 2018.

doi:10.2215/​CJN.10150917

Abstract

Dementia, Alzheimer’s Disease, and Mortality after Hemodialysis Initiation

Background and objectives

Older patients with ESKD experience rapid declines in executive function after initiating hemodialysis; these impairments might lead to high rates of dementia and Alzheimer’s disease in this population. We estimated incidence, risk factors, and sequelae of diagnosis with dementia and Alzheimer’s disease among older patients with ESKD initiating hemodialysis.

Design, setting, participants, & measurements

We studied 356,668 older (age ≥66 years old) patients on hemodialysis (January 1, 2001 to December 31, 2013) from national registry data (US Renal Data System) linked to Medicare. We estimated the risk (cumulative incidence) of diagnosis of dementia and Alzheimer’s disease and studied factors associated with these disorders using competing risks models to account for death, change in dialysis modality, and kidney transplant. We estimated the risk of subsequent mortality using Cox proportional hazards models.

Results

The 1- and 5-year risks of diagnosed dementia accounting for competing risks were 4.6% and 16% for women, respectively, and 3.7% and 13% for men, respectively. The corresponding Alzheimer’s disease diagnosis risks were 0.6% and 2.6% for women, respectively, and 0.4% and 2.0% for men, respectively. The strongest independent risk factors for diagnosis of dementia and Alzheimer’s disease were age ≥86 years old (dementia: hazard ratio, 2.11; 95% confidence interval, 2.04 to 2.18; Alzheimer’s disease: hazard ratio, 2.11; 95% confidence interval, 1.97 to 2.25), black race (dementia: hazard ratio, 1.70; 95% confidence interval, 1.67 to 1.73; Alzheimer’s disease: hazard ratio, 1.78; 95% confidence interval, 1.71 to 1.85), women (dementia: hazard ratio, 1.10; 95% confidence interval, 1.08 to 1.12; Alzheimer’s disease: hazard ratio, 1.12; 95% confidence interval, 1.08 to 1.16), and institutionalization (dementia: hazard ratio, 1.36; 95% confidence interval, 1.33 to 1.39; Alzheimer’s disease: hazard ratio, 1.10; 95% confidence interval, 1.05 to 1.15). Older patients on hemodialysis with a diagnosis of dementia were at 2.14-fold (95% confidence interval, 2.07 to 2.22) higher risk of subsequent mortality; those with a diagnosis of Alzheimer’s disease were at 2.01-fold (95% confidence interval, 1.89 to 2.15) higher mortality risk.

Conclusions

Older patients on hemodialysis are at substantial risk of diagnosis with dementia and Alzheimer’s disease, and carrying these diagnoses is associated with a twofold higher mortality.

https://neurosciencenews.com/dementia-dialysis-9683/

AMANTADINE EXTENDED-RELEASE FOR DYSKINESIA

11th August 2018

Amantadine extended-release (ER) capsules (GOCOVRITM) are approved in the USA for the treatment of dyskinesia in people with Parkinson's Disease who are taking L-dopa. With a recommended dosage of 274 mg once daily at bedtime, the new formulation of amantadine allows a more gradual time to peak plasma amantadine concentration and higher drug concentrations in the morning and throughout the day, which is the time period when L-dopa induced dyskinesia (LID) is the most problematic. 

For more information go to :https://www.rxlist.com/gocovri-drug.htm

After 13 weeks and 25 weeks amantadine ER capsules significantly improved L-dopa-induced dyskinesia (LID), while also increasing ON time without troublesome dyskinesia and reducing OFF time and ON time with troublesome dyskinesia from the morning and throughout the day. After 64 weeks patients previously treated with amantadine ER maintained their improvements.

Amantadine ER was generally well tolerated, with most of the adverse events (AEs) of amantadine ER being transient and mild or moderate in severity. The most common adverse events were treatment related and had an incidence of more than 15%.

Reference : CNS Drugs [2018] Aug 7 [Epub ahead of print] (J.Paik, S.J.Keam) Complete abstract : http://www.ncbi.nlm.nih.gov/pubmed/30088203

http://www.viartis.net/parkinsons.disease/news/180811.pdf

Diabetes Linked to Risk for Parkinson’s Disease

August 11, 2018

Diabetes linked to risk for Parkinson’s disease: people with type 2 diabetes may have an increased risk of having a diagnosis of Parkinson’s later in life, according to a large study. In addition, the risk may be higher for younger people and those with complications from the disease.

While the association between diabetes and Parkinson’s disease is known, this study adds to our understanding of who is most at risk.

New research suggests that those with T2DM can face a significantly higher risk of developing Parkinson’s disease later in life. Parkinson’s is a progressive disease that affects a part of the brain that helps control movement. In type 2 diabetes, a person either doesn’t make enough insulin to effectively turn glucose into energy or the cells don’t use the insulin as well as they should.

This result comes from the finding of a link after tracking Parkinson’s diagnoses among millions of  patients with and without diabetes. Having diabetes can affect the immune system and increase the risk for other diseases.

The study author, Dr. Thomas Warner, said that after accounting for conditions that might mimic Parkinson’s, the research showed that those with type 2 diabetes had a 32% greater risk of later developing the progressively debilitating neurological disorder.

Escalated risk was even more dramatic among younger diabetes patients, ages 25 to 44, who were found to face a fourfold greater likelihood of eventually developing Parkinson’s, according to the report.

Adults with diabetes who had already developed diabetes-related health complications — including damage to the retina, kidneys, or nerves — faced a 49% hike in their Parkinson’s risk.

Although the study could not prove a cause-and-effect relationship, Warner cited two possible reasons for a link between the two diseases.

First, he said, there could be “shared genetic predisposition to develop [both] type 2 diabetes and Parkinson’s.” And then “there may be shared pathways in leading to development of diabetes and Parkinson’s.” While the exact nature of such a connection remains unclear, Warner suggested it might involve the insulin production and glucose control problems that characterize diabetes.

For their study, the investigators used data to identify 2 million British patients newly diagnosed with diabetes from 1999 through 2011. This group was then compared with 6 million British patients who had initially sought care during the same time frame for non-diabetes related issues, such as sprains, varicose veins, appendectomies, or hip replacements.

The researchers found that just over 14,000 of the 2 million patients in the diabetes group were later diagnosed with Parkinson’s, compared with about 21,000 of the 6 million others. That translated into a more than 30% greater risk for Parkinson’s among those with diabetes, the researchers said.

Among patients with diabetes 25 to 44 years old, 58 of over 130,700 people developed Parkinson’s, compared with 280 out of nearly 2.6 million similarly aged people without diabetes. That translated into a fourfold greater Parkinson’s risk among those with diabetes, the researchers said.

“Unlike most tissues in the body, brain cells are almost totally reliant on glucose as a source of energy,” Warner noted. “So if there is a problem in how insulin controls the use of glucose by cells, this may affect certain groups of brain cells selectively.”

Restoring the brain’s ability to use insulin could potentially have a protective effect on the brain,” said Warner. “It is possible that a link between type 2 diabetes and Parkinson’s could affect future diagnosis and treatment of these diseases. Whether it is genetics that may play a role in the development of these diseases or they have similar pathways to development needs to be investigated further.”

Warner is a professor of clinical neurology with the University College London Institute of Neurology, as well as the Queen Square Brain Bank for Neurological Disorder, both in London.

he study authors didn’t examine how diabetes may contribute to Parkinson’s, but prior research does offer clues. We know that neurons consume much more energy than other cells in our bodies. Mitochondria, the powerhouses of our cells, convert glucose into useable energy for cells. In Parkinson’s and other neurodegenerative diseases, mitochondria can become dysfunctional, which may damage and eventually kill neurons. Dopaminergic neurons — the type involved in Parkinson’s — are particularly vulnerable to mitochondrial dysfunction. Diabetes appears to contribute to this, as can some genetic factors.

Practice Pearls:

• The findings may reflect shared genetic predisposition and/or disrupted shared pathogenic pathways with potential clinical and therapeutic implications.
• Patients with type 2 diabetes have a 31% greater risk of developing Parkinson’s than people without diabetes.
• For T2DM patients who are experiencing complications from their diabetes, the risk for Parkinson’s raises to 49% greater risk and 400% for younger people (ages 25-44) with T2DM.

Online issue of Neurology®. June 13, 2018

http://www.diabetesincontrol.com/diabetes-linked-to-risk-for-parkinsons-disease/

BOXING PROGRAM HELPS PEOPLE WITH PARKINSON’S DISEASE – VOICE OF AMERICA

August 10, 2018

Parkinson's patient Jim Coppula gets some pointers from his daughter Ellen as he works out on a bag during his Rock Steady Boxing class in Costa Mesa, California September 18, 2013.

The physical fitness business Rock Steady Boxing NOVA gym opened in McLean, Virginia last December.

That was the good news for 75-year-old Neil Eisner. He was diagnosed with Parkinson’s disease six years ago. He finds the boxing a helpful way to fight back against the disease.

Parkinson’s disease affects the nervous system and causes people's muscles to become weak and their arms and legs to shake.

Rock Steady Boxing, or RSB, was designed to help people with Parkinson's. The exercises in the program are meant to build specific skills.

One involves hitting a bag to work on strength. Another has trainees crawling across the floor. Eisner says the exercises help him perform everyday tasks like moving around and getting in and out of bed.

Some strengthening exercises work the vocal cords.

Eisner said his trainer is working with him to speak out loudly.

"One of the things interestingly enough is you [Parkinson's patients] tend to have a lower voice. When you have that lower voice, people can't hear you, you don't realize it. So, he asks and is getting us to bring up our voice clearly and more loudly."

Staying active important

Private trainer Alec Langstein likes working with older people because he understands their health issues and the need for them to stay active.

"My aunt has a gym in Westchester, New York, and she does a Rock Steady Boxing program there," he said. "She invited me up to her gym to check out the program. She thought it would be a perfect fit for what I do. I helped out with a few classes, and it was just, I thought, an amazing program."

Parkinson's patient Jim Coppula works out in the ring with boxing coach Justice Smith (L) during his Rock Steady Boxing session in Costa Mesa, California September 16, 2013.

The Rock Steady Boxing nonprofit company was created in 2006 by lawyer Scott C. Newman. He was looking for ways to do physical exercise after being diagnosed with Parkinson's at the age of 40. Since then, more than 500 boxing programs have been started in the U.S. and around the world.

Langstein went to the organization's headquarters in Indianapolis, Indiana, to become an RSB-certified trainer. A few months later, he opened his Rock Steady Boxing NOVA gym.

Langstein said that the RSB program centers attention on teaching balance and coordination between the hand and eye. It also teaches reaction and foot movement. 

“So when I yell out certain numbers, they have to move and react at the same time. So, the brain and the body is working together.”

He added that it also helps people release some of the anger they may have from having the disease.

​Improving quality of life

To understand how RSB can help Parkinson's patients, physical therapist Danielle Sequira says it is important to know what causes the symptoms.

Parkinson's patients Jerry Held (L), Jim Coppula (2nd L) and Dan Cathcart (3rd L) stretch as they begin their workout at Rock Steady Boxing in Costa Mesa, California September 16, 2013.

She said that Parkinson's affects the dopamine-producing cells in the brain. Dopamine is a chemical that is important to the operation of the nervous system. A loss of dopamine can make movement difficult.

Boxing and other exercises do not cure the disease or stop the loss of dopamine. But, they can improve the patient's life experience.

Sequira said research shows that exercise helps the brain use dopamine better. She adds that, after working with Parkinson’s patients, her goal is for them to start an exercise program out in the community.

RSB seems to have helped Victoria Hebert reduce the symptoms of her Parkinson's. She has a tremor, or shake, in her left hand, and says some situations can make the shaking worse.

"Being cold, being hot, sitting with a crowd that I'm not real comfortable with, I'll start shaking. I end up having to sit on my hand just to keep it still." 

But with this crowd, Hebert feels no need to hide the disease.

"That's the big part of it, sharing experiences with others," she said.

"I have to say…Over eight years of time I've never met another person with Parkinson's. Then, I came here, and it was like a whole class of 20, 25 people with it. It was kind of surprising to me, kind of surprising that I, myself, didn't reach out to anybody before that."

https://learningenglish.voanews.com/a/boxing-program-helps-people-with-parkinsons-disease/4506013.html

Specific Biomarkers May Help to Distinguish Parkinson’s Dementia from Dementia with Lewy Bodies

AUGUST 10, 2018  BY JOSE MARQUES LOPES, PHD 

The levels of specific protein biomarkers in the cerebrospinal fluid (CSF) — the liquid surrounding the brain and spinal cord — can distinguish patients with Parkinson’s disease dementia (PDD) from those with dementia with Lewy bodies (DLB) regardless of dementia stage, according to a new study.

The research, “Cerebrospinal fluid markers analysis in the differential diagnosis of dementia with Lewy bodies and Parkinson’s disease dementia,” appeared in the journal European Archives of Psychiatry and Clinical Neuroscience.

Brain protein clumps known as Lewy bodies are characteristic of both Parkinson’s and DLB.

Current practice gives a DLB diagnosis if dementia occurs before or during the first year of parkinsonism, a general term for neurological disorders that cause movement problemssimilar to those of Parkinson’s patients.

As such, a follow-up is essential to differentiate between PDD and DLB. However, the overlap of clinical symptoms and the difficulty in establishing when specific symptoms start make this distinction challenging and impacts treatment.

A percentage of DLB cases share a varying extent of pathological features with Alzheimer’s. But, unlike in that disease, no specific CSF biomarkers  have been validated for DLB and PDD. Researchers, for this reason, assessed the diagnostic potential of widely accepted CSF biomarkers across dementia stages to differentiate between DLB and PDD.

A total of 136 patients, all being treated at University Medical Center, Göttingen, Germany, underwent routine laboratory testing and a spinal tap to collect CSF. Cognitive examinations were preformed using the Mini-Mental State Exam (MMSE), and 65% of these patients were also tested with the Montreal Cognitive Assessment (MoCA), and the Clinical Dementia Rating (CDR).

The group included 51 people (31 men) with a diagnosis of probable DLB — 6 later confirmed — 53 with Parkinson’s, and 32 who were cognitively intact. Thirty-one of the Parkinson’s patients met the criteria for PDD (16 women and 15 men). Patients exhibiting dementia were classified as mild, moderate or severe.

CSF samples were tested for the proteins amyloid-beta1–42, tau, phoshorylated tau (a modified form of the tau protein), neuron-specific enolase (NSE) — a predictor of severity and neurobehavioral outcome after acute stroke, and implicated in Alzheimer’s — and S100B, a marker of brain damage. Of note, both amyloid-beta and phoshorylated tau form clumps in the brains of Alzheimer’s and Parkinson’s patients.

Levels of tau and amyloid-beta1–42, as well as the phosphorylated tau/total tau ratio were helpful in distinguishing between DLB and Parkinson’s patients with or without dementia.

Specifically, tau levels were higher in DLB than in Parkinson’s patients regardless of cognitive status, and were also higher in Parkinson’s patients with dementia than those without it.

DLB patients had lower levels of both amyloid-beta1–42 and phosphorylated tau/total tau ratio than did Parkinson’s dementia patients. This ratio was lower in DLB patients with mild and moderate dementia.

Levels of tau and phosphorylated tau protein in patients’ CSF reflected the severity of dementia in both DLB and PDD patients. Tau ratio enabled a distinction between Parkinson’s patients with mild and moderate dementia, and was lower in those with severe dementia than those with mild dementia.

Lower levels of amyloid-beta1–42 correlated with a rapid disease course in DLB but not in PDD. Both DLB and Parkinson’s patients with dementia showed elevated levels of S100B in comparison to healthy controls — indicating brain damage.

For both DLB and PDD, patients with less than a year of disease duration showed a trend toward higher tau, phosphorylated tau and NSE as opposed to lower amyloid-beta1–42  when compared to those whose disease had been diagnosed earlier.

Nevertheless, only values for amyloid-beta1–42 were lower in DLB patients whose dementia was confirmed less than one year after their primary diagnosis, compared to those diagnosed with PDD.

“These results have clinical relevance by suggesting that the descent of CSF [amyloid-beta1–42] values mainly in rapid disease course might have a prognostic significance,” the researchers wrote.

“[W]e conclude that CSF profile with the appropriate clinical context could be effective in distinguishing DLB from PDD patients, regardless of the severity of dementia,” they added.

https://parkinsonsnewstoday.com/2018/08/10/biomarkers-help-distinguish-parkinsons-dementia-from-dementia-with-lewy-bodies-in-study/

Specific Area of Brain Involved in Motor Issues, Slow Thinking in Parkinson’s, Mouse Study Shows

AUGUST 10, 2018      BY MARTA FIGUEIREDO IN NEWS.

Nerve cell damage in a specific area of the brain impairs motor function and slows thought, both of which are symptoms of Parkinson’s disease, a mouse study finds.

The study, “Loss of glutamate signaling from the thalamus to dorsal striatum impairs motor function and slows the execution of learned behaviors,” was published in NPJ Parkinson’s Disease.

Parkinson’s disease is caused by the progressive loss of brain nerve cells — in particular, those that produce dopamine, a molecule essential for nerve cell communication — as well as the abnormal accumulation of alpha-synuclein-containing Lewy bodies that induce nerve cell damage.

While a hallmark of Parkinson’s disease is the loss of dopamine-producing nerve cells in a brain area called the substantia nigra, known to be involved in motor function, increasing evidence shows that other areas of the brain are also impacted both at Parkinson’s onset and throughout the course of the disease.

Nerve cells in the substantia nigra send dopamine signals to the dorsal striatum, a region of the brain also involved in the control of movement. The loss of dopamine signaling in Parkinson’s disease leads to dorsal striatum dysfunction and to the motor problems seen in Parkinson’s patients.

However, the dorsal striatum also receives signals from other areas of the brain, such as the thalamus, which relays motor signals to the dorsal striatum through glutamate, another signaling molecule. The thalamus is also known to play a crucial role in memory, executive function, and attention.

Several studies have reported that Parkinson’s patients present with Lewy bodies, loss of nerve cells, and changes in the structure and activity of the thalamus.

These data suggest that nerve cell damage in the thalamus may be involved in the development of Parkinson’s symptoms.

Researchers have now evaluated whether the disruption of glutamate-dependent thalamus signaling to the dorsal striatum results in the cognitive and motor deficits characteristic of Parkinson’s.

The team generated genetically modified mice that allowed the induction of loss of glutamate signaling specifically between the thalamus and the dorsal striatum. A battery of motor and behavioral tests were performed in these mice to assess motor function, visuospatial function, executive function, attention, and working memory.

Modified mice showed significant motor coordination deficits, compared with healthy mice, suggesting that impaired thalamus-dorsal striatum signaling is involved in motor deficits.

In addition, while the disruption of thalamus-dorsal striatum signaling did not result in an apparent cognitive impairment, these mice took longer to process cues and new environments and were slower at carrying out tasks than healthy mice.

These results suggest that the loss of glutamate signaling between the thalamus and dorsal striatum led to slower processing reaction times, which resemble “bradyphrenia, the slowness of thought that is often seen in patients with PD and other neurological disorders,” the researchers wrote.

Slow thought can cause bradykinesia — slowness of movements or difficulty moving the body quickly on demand — which is also a symptom of Parkinson’s.

The team noted that the results highlight the involvement of glutamate-producing nerve cells in the thalamus that signal to the dorsal striatum in behaviors of mice that resemble slowness of thought and movement, indicating that the loss of function of these cells contribute to cognitive and motor deficits in Parkinson’s disease.

This may explain why some of the Parkinson’s therapies that target dopamine signaling have limited therapeutic effects in terms of patients’ cognitive function.

The researchers added that new therapies acting on other communication molecules besides dopamine are needed to target cognitive symptoms, and that their genetically modified mice may serve as a model to test those approaches.

https://parkinsonsnewstoday.com/2018/08/10/specific-brain-area-involved-motor-issues-slowness-thought-study/

Reduced levels of chaperone protein may have implications for development of Parkinson’s disease

August 10, 2018

Reduced levels of a chaperone protein might have implications for the development and progression of neurodegenerative diseases such as Parkinson's disease and Lewy body dementia, according to new research from investigators at the University of Alabama at Birmingham. Findings published in the Journal of Neuroscience indicate that the reduction of chaperone protein 14-3-3 could lead to misfolding and spread of a key brain protein from one brain region to another.

Genes are encoded to make a particular protein, using DNA as a set of instructions for how the protein is to be assembled. A protein, a long string of amino acids, needs to assume its correct shape in order to interact with other structures. Proteins that fail to or are prevented from assuming the proper shape -; a process called misfolding -; are implicated in a number of disease conditions.

Alpha-synuclein is a highly expressed brain protein. While its actual function is not well understood, it appears to be involved in communication between neurons. What is understood is that, when alpha-synuclein misfolds, it forms neuronal aggregates, or inappropriately shaped proteins, that contribute to the death of neurons and are associated with the development of Parkinson's and Lewy body dementia.

UAB researchers led by Talene Yacoubian, M.D., Ph.D., an associate professor in the Department of Neurology, launched an investigation of the role of 14-3-3, a chaperone protein, on alpha-synuclein. Chaperone proteins are involved in regulation of other proteins -; in essence, a chaperone protein helps another protein assume its proper shape to perform its proper function.

14-3-3s are a family of seven chaperone proteins in humans. In particular, Yacoubian's group looked at one member of that family, 14-3-3θ, referred to as 14-3-3 theta. In two elegantly designed studies, the researchers investigated the role of 14-3-3θ on misfolding and spread of alpha-synuclein.

In one study, 14-3-3θ was withheld or inhibited in neurons. Observations of alpha-synuclein showed an increase in misfolded proteins, an increase in the spread of aggregates from neuron to neuron, and increased neuronal death. The second experiment involved boosting the amount of 14-3-3θ, which produced a decrease in misfolded alpha-synuclein and limited the spread of the protein across neurons and reduced neuron death.

"Our findings indicate that 14-3-3θ plays an important role in the management of alpha-synuclein, keeping it in a more normal folded state and preventing the spread of aggregates across the brain," Yacoubian said. "The study suggests that 14-3-3θ may be a suitable target for efforts to slow the progression of neurodegenerative diseases, although more work is needed."

One tantalizing connection to diseases such as Parkinson's and Lewy body dementia is that both are primarily diseases of aging.

"There is evidence that 14-3-3θ may be age-dependent and the amount present in the brain may decrease with age," Yacoubian said. "If subsequent research confirms our findings of its role on preventing misfolding of alpha-synuclein, we may have a viable target for intervention in neurodegenerative diseases that are also age-related."

Yacoubian says studies of 14-3-3θ using animal models are already underway, and she is collaborating with the drug development arm at Southern Research Institute to find a compound that can boost the production of 14-3-3θ and is suitable for use in human studies. ​

Source:

http://www.uab.edu/news/research/item/9669-study-identifies-chaperone-protein-implicated-in-parkinson-s-disease

https://www.news-medical.net/news/20180810/Reduced-levels-of-chaperone-protein-may-have-implications-for-development-of-Parkinsone28099s-disease.aspx