An Alzheimer’s study used electrostimulation to evoke vivid memories – here’s what it could mean

September 20, 2019  USF,   Wissam Deeb  Assistant Professor of Neurology, 

Alzheimer’s disease is one of the most dreaded diagnoses, and the fear is particularly acute among older people. This complex brain disorder, which usually affects older individuals, can cause many cognitive disabilities, most notably memory impairment.

About 5.7 million Americans are living with Alzheimer’s disease. In addition, millions of loved ones and caregivers are affected, with some estimates indicating there are as many as 16 million unpaid caregivers. 

As the baby boomer generation has started to turn 65, the number of people diagnosed with this disease is expected to continue to grow.

The available medications don’t help much in the management of memory problems and associated behavioral changes. There is a clear need for more effective treatment options. 

As a response to this demand, a group of researchers tested the use of deep brain stimulation to improve memory and cognition in individuals with Alzheimer’s disease (ADvance trial). While the long-term benefit on memory was not as robust as expected, almost half of the patients reported recalling past experiences. This is a notable observation as it occurred in individuals with memory problems. Furthermore, it can improve researchers’ understanding of the way memory is formed and retrieved.

Deep brain stimulation for Alzheimer’s disease

The fornix, a tiny part of the brain, may hold some clues to memory loss. Wissam Deeb, CC BY-SA

Deep brain stimulation is an FDA-approved treatment for many neurological disorders such as Parkinson’s disease. It consists of implanting, through the skull, stimulating electrodes, with electric wires, into deep structures inside the brain. These electrodes are then connected to pacemaker-like devices in the patient’s chest. The pacemaker devices produce an electric signal that modifies the brain activity and improves the targeted symptoms, such as tremor in Parkinson’s disease.

In Alzheimer’s disease, the memory circuits in the brain, which include a notable structure called the fornix, are affected. The fornix is important in remembering personal events and concepts. In the ADvance trial, the researchers evaluated if deep brain stimulation at the level of the fornix ameliorated the memory of 42 subjects with Alzheimer’s disease. They found a possible improvement in memory only in those older than 65; researchers saw no benefit when evaluating all the participants. Learning from this experience, the researchers are embarking on another trial called ADvance II.

But there’s more to the story

Recently, researchers involved in the ADvance trial and I wrote an article for the New England Journal of Medicine which analyzes an interesting observation from the trial: About half of the subjects spontaneously reported recalling vivid memories. These were detailed and unsolicited memories from their past. These memories occurred only for a short period of time and their presence did not equate to a long-term improvement in memory. A key takeaway is that deep brain stimulation at the fornix can induce memories, at least briefly, although the implications for treatment and long-term effects remain unclear.

Of the 42 subjects who participated in the ADvance trial, 20 described previous events during the first session of evaluating their deep brain stimulation for possible side effects. During these evaluation sessions, the stimulation intensity and location were varied to determine the optimal settings. 

Analyzing data from the first trial, we counted 85 unique memory recollections of varying detail. Twenty-nine recollections had elaborate details about the place and time of these memories. For example, one person recalled a vacation in Aruba including the taste of lime in the margarita and feeling “buzzed.” Some of the recollections were from decades ago. 

They were memories that the participants did not think of for many years, and they carried a lot of emotional value. I found it interesting that, as the intensity of deep brain stimulation stimulation increased, the detail of the memories increased. The detail was limited only by the development of unwanted side effects of more intense deep brain stimulation stimulation. For example, one person initially described a generic recollection of “helping a guy find something on his property” which then evolved, as the stimulation intensity was increased, into remembering that this was at night, around Halloween, and that he was with his son.

The 20 subjects who developed these memory recollections when deep brain stimulation was turned on did not do better than those who did not have them on cognitive testing. Furthermore, there was no association between having these recollections or their intensity and the cognitive and memory outcomes. Hence, the implications of these findings for treatment remain unclear. 

Despite these limitations, these findings offer a couple of insights. First, they add to the accumulated knowledge about the areas of the brain involved in memory, including in brains of individuals with memory disorders. Second, they reveal that it is possible, albeit maybe only temporarily, for individuals with Alzheimer’s disease to access stored memories with electrical stimulation that were not previously accessed possibly due to the brain changes associated with the disease.

Further work and research is needed to clarify the role of these electrically induced memories. Do they last long after deep brain stimulation implantation? How can different memories be induced? Why did only half of the subjects develop such recollections? How can researchers use these memories in helping develop deep brain stimulation and other treatments for Alzheimer’s disease?

This work provides further insight into the effect of electrical stimulation in the area of the fornix in individuals with Alzheimer’s disease. It also provides one more piece of information in the scientific quest to treat this condition. And in the study of Alzheimer’s disease, any new information that may be helpful is welcome news.

http://theconversation.com/an-alzheimers-study-used-electrostimulation-to-evoke-vivid-memories-heres-what-it-could-mean-123253

Yarmouth gearing up for Parkinson SuperWalk on Sept. 28

September 20, 2019

The SuperWalk is a national fundraiser for Parkinson Canada, with walks held across the country. This year’s event will be held in Yarmouth on Saturday, Sept. 28.

YARMOUTH, N.S. — 

On Saturday, Sept. 28, members of the Parkinson Canada Tri-County Patient and Caregiver Support Group will be participating in the Yarmouth SuperWalk. 

This is the 29th year for the SuperWalk, organized by Parkinson Canada, during which thousands of Canadians will be coming together to walk in support of people living with Parkinson’s disease. 

This year Rita Fitzgerald, 61, will take part in Parkinson SuperWalk for the third time. 

“I walk each year because I want to spread awareness of the disease to others,” she says. Fitzgerald wants others to be open about their battle with Parkinson’s. 

“Don’t be afraid to talk about it. It doesn’t need to be a secret.”

The Parkinson Canada Tri-County Patient and Caregiver Support Group meets monthly and provides people support in managing this condition. 

Parkinson’s affects more than 100,000 Canadians, with 25 people being diagnosed every day. The numbers of diagnoses are expected to increase to 51 by 2031. Due to these numbers, Parkinson’s is one of the fastest growing neurological conditions in the world. It is also one of the most prevalent neurodegenerative diseases. 

This means that continued support is needed in order to fund research to find a cure and the SuperWalk is a chance to fundraise for the cause. Since 1981, Parkinson Canada has invested more than $29 million in research.

“We want to thank SuperWalk participants who continue to raise significant funds and increase public awareness of our charity,” says Joyce Gordon, CEO of Parkinson Canada. 

“These funds help us to greatly impact the lives of those living with Parkinson’s, their caregivers and health-care professionals, and offer hope for a future without Parkinson’s. For these individuals, a cure can’t wait.” 

When you walk in a Parkinson Canada SuperWalk you support: research to find a cure and to improve quality of life; advocacy for better public policies and programs to improve the quality of life; information and referral services accessible to anyone, anywhere in Canada; support groups so that all who need information and help receive it from those who can best provide it; and education so that people living with Parkinson's are informed and empowered to live well.

Check-in for the Yarmouth walk on Sept, 28 will be at noon, with the walk starting at 1 p.m. Registration can be completed online: http://www.superwalk.caAbout Parkinson Canada

Parkinson Canada provides services and education to people living with Parkinson’s disease, their families, and the health-care professionals who treat them. Operating since 1965, the organization advocates on issues that concern the Parkinson’s community in Canada. The Parkinson Canada Research Program funds innovative research for better treatments and a cure. A national registered charity, Parkinson Canada fulfils its mission through the generosity of donors and is an accredited organization under the Imagine Canada Standards Program. Parkinson Canada participates in numerous coalitions and partnerships to effectively fulfill its mission.

https://www.novanewsnow.com/news/provincial/yarmouth-gearing-up-for-parkinson-superwalk-on-sept-28-354613/

Glycolysis Inhibitor Could Prevent Cell Death and Excitotoxic Brain Disease

Sep 20, 2019   by Alina Chernova, Gero Discovery Team

An international team of scientists from Gero Discovery LLC, the Institute of Biomedical Research of Salamanca, and Nanosyn, Inc. has found a potential drug that may prevent neuronal death through glucose metabolism modification in stressed neurons. The positive results obtained in mice are promising for future use in humans. The new drug could be advantageous in neurological conditions ranging from amyotrophic lateral sclerosis, Alzheimer’s and Huntington’s diseases, to traumatic brain injury and ischemic stroke. The results have been published in theScientific Reports Journal.

Brain injuries and neurological disorders are among the most significant causes of death worldwide. According to WHO, stroke is the second most common cause of mortality, and more than a third of people who have survived a stroke will have a severe disability.

What is more, as the population ages, millions more people are at risk of developing Alzheimer’s or Parkinson’s diseases in the near future. However, there are no efficient drugs for major neurodegenerative diseases. It is thus critically important to understand the biology of these diseases and to identify new drugs capable of improving quality of life, survival, and, in the best-case scenario, curing the disease completely.

In most tissues in the body, glycolysis is considered an essential metabolic pathway for cell survival since it meets the cell’s energy needs in case of intensive energy consumption. However, in brain tissue, the situation is quite different - individual cell types show distinct glucose metabolism patterns.  In neurons, only a small portion of glucose is consumed via the glycolysis pathway. At the same time, astrocytes provide nutrients to neurons and utilize glycolysis to metabolize glucose. These differences are mostly due to a specialized protein called PFKFB3, which is normally absent in neurons and is active in astrocytes. In the case of certain neurological diseases, stroke being one of them, the amount of active PFKFB3 increases in neurons, which is highly stressful for these cells and leads to cell death.

An international team of researchers led by Peter Fedichev, a scientist and biotech entrepreneur from Gero Discovery, and professor Juan P. Bolaños from the University of Salamanca, suggested and further confirmed in in vivo experiments that a small molecule, an inhibitor of PFKFB3, may prevent cell death in the case of ischemia injury. In experiments using mouse cell cultures, it was shown that the PFKFB3 inhibitor protected neurons from the amyloid-beta peptide, the main component of the amyloid plaques found in the brains of Alzheimer’s disease patients. Subsequent in vivo testing showed that inhibition of PFKFB3 improves motor coordination of mice after stroke and reduced brain infarct volume.

Bolaños commented, “Excitotoxicity is a hallmark of various neurological diseases, stroke being one of them. Our group has previously established a link between this pathological condition and high activity of PFKFB3 enzyme in neurons, which leads to severe oxidative stress and neuronal death.”

“We are glad that our hypothesis that pharmacological inhibition of PFKFB3 can be beneficial in an excitotoxicity-related condition, such as stroke, was confirmed. I would like to note that in our work, we used a known molecule to demonstrate that PFKFB3 blockage has a therapeutic effect. But we have also performed the same experiments with other proprietary small molecule designed in our company and showed that it had a similar effect. There is, of course, still much work to do. We are currently investigating the efficacy of our compounds in models of orphan excitotoxicity-related neurological diseases. We have already obtained good safety results in mice and believe that we will be successful in our future investigations” said Olga Burmistrova, director of preclinical development in Gero Discovery.

The Gero Discovery team is planning to proceed with preclinical trials and to move into clinical trials soon. “These promising results bring hope to dozens of millions of patients suffering from life-threatening neurological diseases. We have started communicating with potential investors and co-development partners and invite interested parties to collaborate on the further development of this breakthrough medicine through the preclinical and early clinical stage” said Maksim Kholin, the Gero Discovery Co-Founder and Business Development Director.

Reference: http://dx.doi.org/10.1038/s41598-019-48196-z

https://www.technologynetworks.com/tn/articles/glycolysis-inhibitor-could-prevent-cell-death-and-excitotoxic-brain-disease-324177

Embracing the Beauty and Serenity of My Sanctuary

SEPTEMBER 20, 2019     BY DR. C 

Sunlight bounces its way through the swaying birches, projecting a shadow picture show on the lawn and garden shed. A light wind causes the fluttering leaves to sing in unison like waves on the shore. A family of hummingbirds — we have given all of them names now — take turns to show off their aerial ballet at the feeder, a few feet from my rocking chair. The gardens are still blooming with cranberry-red coneflowers nestled between large-cupped orange and yellow day lilies. In the distance, I hear the sweet, calming vibrato of our brook. It beckons me to embrace the support revealed within my sanctuary.

Sanctuary can be found and created anywhere. It doesn’t have to be Walden Pond or resemble my description. What is important is the frame of mind used when accessing sanctuary. Sanctuary is that place where the saying, “You get back out what you put in,” truly applies. If I can embrace the awe and beauty of my sanctuary while also experiencing its solitude, safety, serenity, and sacredness, then I know that I am in the right frame of mind.

Sanctuary is more than a sacred physical place. The physical merely signals the senses to be ready for the well-being phenomena. The physical sanctuary supports the emotional and spiritual sanctuary. It is from this inner stance that I seek calm and a trusting openness, and prepare to experience the journey. I have a relationship with my sanctuary, and this “agreement” is the first step to incorporating sanctuary into a wellness plan.

Architects realize the importance of creating healthy living and work environments. Designs for buildings and the areas they occupy, whether in a rural or urban setting, are incorporating a sense of sanctuary for well-being. Providing for “green space,” buffers, and integration with the natural environment are key concepts for architects. “Architecture helps shape the quality of our environments and can contribute to health and happiness,” writes Karl Johnson in the Guardian. Sanctuary is rooted in the beauty of nature. The “N” in the CHRONDI Creed, stands for “nature” and its health benefits.

Let me share my story of sanctuary. The week had been hectic, even busier than usual. It started with a trip to my general medical provider’s office for fasting lab work. It’s almost a two-hour drive on an empty stomach until after the labs are drawn, which throws off my Parkinson’s medications. The next day, we took a trip to Boston for my appointment at a Veterans Affairs healthcare facility. That trip takes two days, so we usually drive down the day before the appointment to break up the journey. We stay at a hotel, then arise the next morning to complete the four-hour drive to the clinic.

The appointments are never fun. At least this one didn’t require the providers to poke, prod, or inject. Well, maybe some poking, but no injections. Then we drove home, another four hours on the road. With my rigid Parkinson’s, every minute of travel increases my discomfort. No time to rest because I’m back at the doctor’s office a day later for the lab results.

The day after the doctor’s appointment, we run errands, and my partner hand-delivers her application to the state offices for “designated caregiver” status. We didn’t have the energy to attend a live theater presentation on Galileo or the monthly get-together for the New England Santa Society. Or celebrate our anniversary. We make decisions every week about where to spend our free time; this includes letting go of some plans in favor of time spent with sanctuary.

Weeks like the one that I describe are more difficult for me. I require several days to recuperate and recover. The fatigue is almost overwhelming, preventing me from returning to my projects as much as I would like. My mind is tired, my body drained, and my soul seeks out my sanctuary. I don’t need to have faith that sanctuary will help; I know from personal experience that it will.

You can create a sanctuary in your home, in a favorite room or comfortable chair. You can build a garden along a walkway. Perhaps you will find, as I do, that I can create several different areas, each unique to the landscape, plants, and season. I enjoy the beauty of each special place within my quiet sanctuary. What is important is your ability to embrace that special sacred physical place, the sanctuary that offers you the greatest support for well-being.

***

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.

https://parkinsonsnewstoday.com/2019/09/20/embracing-sanctuary-well-being-nature/

$2.8M NIH Grant Targets Proteins Involved in Brain Disorders

SEPTEMBER 20, 2019   BY MARISA WEXLER 

The National Institute of Neurological Disorders and Stroke, of the National Institute of Health (NIH), has awarded a large grant to researchers who are seeking to understand the molecular structure of toxic proteins that drive brain disorders.

Irregular clumps of certain proteins are thought to be the root cause of several neurological disorders: alpha-synuclein and amyloid-beta proteins are linked with Parkinson’s disease and Lewy body dementia (which often occur simultaneously), and amyloid-beta and tao are involved in Alzheimer’s disease.

The new grant awards $2.8 million over five years to study the structure of these proteins. The project is being led by researchers at Mayo Clinic’s Florida Campus and at Columbia University in New York.

The researchers plan to use new imaging technologies, namely single-particle cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), to investigate these proteins in more detail than ever before.

Cryo-EM — a technology that shared the 2017 Nobel Prize in Chemistry — uses beams of electrons to investigate the structure of proteins with atomic-level resolution. Researchers plan to use it to view proteins in samples of brain tissue from people with neurological disorders like Parkinson’s.

Cryo-ET allows for the visualization of proteins within living neurons, which  researchers hope will provide important information about how these protein clumps end up killing brain cells.

“To truly understand the link between proteins and disease, we must discover how they interact with each other and with the surrounding brain tissue,” one of the researchers who will lead the project, Anthony Fitzpatrick, PhD, a professor at Columbia, said in a press release. “Cryo-EM’s power lies in its ability to reconstruct any protein at the level of individual atoms. This, combined with cryo-ET, which helps us understand how each protein behaves inside individual brain cells will, ultimately, enable us to learn how this behavior causes cells to die,” he said.

“[W]e hope to discover whether different proteins work in concert to spur disease progression,” Fitzpatrick added. “The combined use of cryo-EM and cryo-ET marks a tremendous leap forward from traditional, in vitro methods, which study the proteins’ behavior in a petri dish and thus do not replicate their natural environment.”

“One of the most imperative quests of our time is the understanding of brain function and the mechanisms of neurodegeneration,” said Rui Costa, DVM, PhD, the director of Columbia’s Zuckerman Institute. “This endeavor will allow us to have unprecedented insight into the 3D molecular structure of the aggregates that form in many neurodegenerative disorders, which ultimately can be critical for early diagnosis, prevention and treatment of these disorders.”

https://parkinsonsnewstoday.com/2019/09/20/nih-grant-targets-proteins-involved-in-brain-disease/

Rhode Island Professor Receives More Funding for ‘Smart Glove’ for Parkinson’s Patients

SEPTEMBER 20, 2019     BY MARY CHAPMAN IN NEWS.

The National Science Foundation (NSF) has awarded a University of Rhode Island (URI) professor nearly $250,000 to help commercialize a “smart glove” for Parkinson’s disease patients.

Kunal Mankodiya, PhD, an associate professor of engineering, is developing the glove that can capture wearers’ movement data. Designed for those with PD or other movement disorders, the technology can help physicians customize patients’ exercise and treatmentregimens.

The two-year project grant is through the NSF’s Partnerships for Innovation program, which helps researchers accelerate innovations that address significant societal needs. The project received NSF funding earlier.

“This funding will enable us to take a deep dive into the world of fusing different domains, including conductive fabrics, wearable electronics, human-factors design and smart textile manufacturing,” Mankodiya said in a press release. “I’m glad that the NSF created such grant programs where innovative technologies could find their way to the marketplace over the years.”

It’s been three years since Mankodiya, with the help of students in his Wearable Biosensing Lab, designed the first prototype of the glove. “We’ve performed significant research on the smart gloves over the years. We decided that it’s time to transition this technology from research to market. However, the transition is not straightforward. It will require very focused, narrow research to finalize the physical, digital and analytical components of the smart gloves,” he said.

Nick Constant has been there since the start. The URI electrical engineering doctoral student designed the proof-of-concept glove that earned the original NSF grant. Along with Mankodiya, he also wrote the new grant proposal. “Its ultimate outcome seemed clear from the beginning, but building a new technology takes time and testing,” he said. “We have seen this glove go from a hopeful idea to gaining traction in reality through different design iterations and consultations with stakeholders.”

Constant’s charge these days is to find project collaborators knowledgeable about areas such as manufacturing, supply chains and medical device regulations. Ultimately, the team wants an affordable glove that’s relatively easy to manufacture.

Neurologist Umer Akbar, MD, project collaborator and co-director of Rhode Island Hospital’s Movement Disorders Program, specializes in those living with Parkinson’s, and sees a definite need for the wearable device. “The challenge with studying the many symptoms of the disease is that they fluctuate throughout the day,” he said. “The short window physicians have into their patients’ lives is often inadequate to verify the symptoms, so we sought to develop wearable technology that can remotely and objectively provide clinical data which can help us better treat our patients.”

In a pilot study to take place in Mankodiya’s lab, at Rhode Island Hospital, and in patients’ homes, up to 30 Parkinson’s patients will try the glove.

Andrea Hopkins has worn the glove a few times since its development. Diagnosed with Parkinson’s in 2002, the former URI assistant vice president of public affairs eagerly awaits the finished version.

“There is no cure for Parkinson’s disease, but if doctors can monitor their patients remotely using the smart glove, it would enable them to assess how the medications are working,” she said.

Many stand to benefit from the glove’s successful development. The neurodegenerative disorder affects roughly 1 million U.S. residents, and more than 10 million individuals globally.

https://parkinsonsnewstoday.com/2019/09/20/smart-glove-funding-parkinsons-rhode-island/

Eisai and Meiji Announce Parkinson's Disease Treatment Equfina Tablets (Safinamide Mesilate) Approved In Japan

September 20, 2019

Eisai Co., Ltd. and Meiji Seika Pharma Co., Ltd. has announced the manufacturing and marketing approval in Japan for the indication of improvement of wearing-off phenomenon in patients with Parkinson's disease under treatment with a drug containing levodopa for Equfina TABLETS (safinamide mesilate, "safinamide"), which was developed for use in the treatment of patients with Parkinson's disease was obtained. In Japan, Meiji holds the manufacturing and marketing approval for safinamide, and Eisai exclusively sells the safinamide.

Parkinson's disease is a neurodegenerative disease which causes motor impairment, with symptoms including tremors in the limbs, muscular rigidity and shuffling gait. It is caused by degeneration of the dopamine nervous system, which leads to a shortage of dopamine, a neurotransmitter in the brain. There are approximately 200,000 patients suffering from Parkinson's disease in Japan(1), and the number of patients is increasing due to the aging of the population.(1), (2) Drugs containing levodopa are widely used to treat Parkinson's disease by replenishing the brain's supply of dopamine. However, as the disease progresses, levodopa's duration of effect ("on" time) decreases, and there are cases where patients may experience wearing-off phenomena, a return of Parkinson's disease symptoms before the next dose. Safinamide through its main mechanism of action as a selective monoamine oxidase B (MAO-B) inhibitor, increases the density of endogenous dopamine and exogenous dopamine from levodopa-containing drugs in the brain.

This manufacturing and marketing approval is based on a double-blind, placebo-controlled Phase II/III study (study ME2125-3) to evaluate the efficacy and safety of safinamide as add-on therapy and an open label Phase III study (study ME2125-4) to evaluate the safety and efficacy of long-term administration of safinamide in Japanese patients with Parkinson's disease with wearing-off phenomena who are currently receiving levodopa, as well as global clinical trials.

In study ME2125-3, the change in mean daily "on" time from baseline to 24 weeks of the treatment phase, which is the primary endpoint, of treatment with safinamide 50 mg and 100 mg were statistically significant compared to placebo-controlled treatment. The most common adverse drug reactions (ADRs) (incidence 3% and higher) observed with patients with safinamide 50 mg and 100 mg were dyskinesia and visual hallucination. Also in study ME2125-4, with regard to the change in mean daily "on" time from baseline to 52 weeks of the treatment phase, the "on" time with long-term administration of safinamide was extended, and showed the continued effectiveness. The most common ADRs (incidence 3% and higher) observed with patients were dyskinesia, falls, and constipation.

By providing Equifina TABLETS as a new option for Parkinson's disease treatment, Eisai and Meiji will make further contributions to address the diverse needs of, and increase the benefits provided to, Parkinson's disease patients and their families.

About Eisai

Eisai Co., Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. We define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call our human health care (hhc) philosophy. With approximately 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realize our hhc philosophy by delivering innovative products in various therapeutic areas with high unmet medical needs, including Neurology and Oncology.

Furthermore, we invest and participate in several partnership-based initiatives to improve access to medicines in developing and emerging countries.

For more information about Eisai Co., Ltd., please visit www.eisai.com

http://health.einnews.com/article/496918429?lcf=Hzf-KE6h-Xmcpvzwcdl3CuzbRmZ8XaTUdg3y3lN96pg%3D

‘Exergaming’ on Stationary Bicycle Eased Parkinson’s Motor Problems

SEPTEMBER 19, 2019    BY JOSE MARQUES LOPES, PHD 

Exercising at home with a stationary bicycle — using a motivational app and remote supervision to increase compliance — eases motor complications in patients with mild Parkinson’s disease and improves their cardiovascular health, according to results from a clinical trial.

Findings from the study, “Effectiveness of home-based and remotely supervised aerobic exercise in Parkinson’s disease: a double-blind, randomised controlled trial,” were published in the journal The Lancet Neurology.

Though high-intensity aerobic exercise has shown motor benefits in people with Parkinson’s, the effectiveness of home-based programs in a broader patient population has not been determined.

A team from Radboud University Medical Center, The Netherlands, designed the “Park-in-Shape” intervention that incorporates virtual reality software and real-life videos — a so-called “exergaming” approach — to make exercising on a stationary bicycle at home more engaging.

Overall, the single-center, randomized trial (NTR4743) tested whether this type of aerobic exercise would improve motor function in patients with mild disease severity (a Hoehn and Yahr stage 2 or less) who were on stable dopaminergic treatment or not yet started on such therapies.

To be included, the patients (ages 30–75) had to exercise less than is recommended for older adults, meaning vigorous exercise over 20 minutes up to two times per week, or moderate exercise over 30 minutes up to four weekly sessions.

The study compared two groups, in which all 130 patients exercised three times per week over six months and were on stable dopaminergic medication (stable dose for at least one month), or were still without treatment and expected not to start treatment within the next month.

But while 65 patients performed stretching, flexibility and relaxation exercises in 30-minute sessions (control group), the other 65 patients exercised for 30 to 45 minutes on the stationary bicycle at home (intervention group). The patients were instructed to cycle at a target heart rate zone, which was gradually increased as the participants became fitter.

All participants had a motivational app with tips for optimal training, support from loved ones, and information to track progress. All were supervised once at home and also remotely every two weeks.

Patients were evaluated during their “on” and “off” states — when dopaminergic medication is still effective, or when it wears off.

Results showed that the patients exercising on the stationary bicycle had  significantly better motor function after six months. Specifically, in their “off” state, the increase in their Movement Disorders Society—Unified Parkinson’s Disease Rating Scale score was 4.2 points lower than that of the controls. Also, unlike the controls, patients on aerobic exercise experienced improvements in cardiovascular fitness by the end of the study.

“Aerobic exercise can be done at home by patients with Parkinson’s disease with mild disease severity and it attenuates [lessens] off-state motor signs,” the scientists wrote.

In contrast, no benefits were seen in non-motor complications such as fatigue, anxiety, depression, or cognitive function, which the researchers attribute to the short duration of the intervention.

Over the span of the study, the mean number of aerobic exercise sessions was 54, while that of the control sessions was 60. This corresponds to 75% and 83% of the expected 72 sessions for each group, respectively.

“We were pleasantly surprised that people with Parkinson’s disease were able to adhere to their exercise regimes so well,” Nicolien van der Kolk, the study’s lead author, said in a press release. “The beneficial effect on their motor disability was also large enough to be clinically relevant. As such, exercise is a very useful addition to the medication.”

Five patients were lost to follow-up, four of whom were in the cycling group. Ten patients in each group did not complete their assigned intervention, with technical issues being the main reason for discontinuation in the cycling group. However, as they attended the follow-up visit, these patients were included in the analysis.

Eleven patients experienced adverse events (AEs, or side effects) potentially related to the intervention, seven of whom were in the cycling group. These included back or joint pain and palpitations. Three patients discontinued exercise due to AEs.

In turn, the seven serious AEs observed (three in the cycling group) were all unrelated to the program. They included knee and fall-related injuries, hip fracture, and severe dyskinesias, which refer to involuntary, jerky movements.

“This study is very important,” said Bas Bloem, MD, PhD, the study’s principal investigator. “We can now start researching whether much more long-term cycling can also slow the disease progression.”

“Also, this new ‘exergaming’ approach that we have developed is very suitable to achieve long-term improvements in exercise behavior for patients with a range of other disorders that could also benefit from regular exercise,” Bloem said.

“Future studies should establish long-term effectiveness and possible disease-modifying effects,” the researchers concluded.

https://parkinsonsnewstoday.com/2019/09/19/exergaming-home-exercise-stationary-bicycle-motor-problems-parkinsons/

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

SEPTEMBER 19, 2019 BY MARY CHAPMAN IN NEWS.

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 Centersto 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:

https://www.apdaparkinson.org/article/apda-research-funding-2020/

https://parkinsonsnewstoday.com/2019/09/19/parkinsons-organizations-research-grants/