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#AANAM – Data Recorded from PKG Wearable Device May Help Clinicians Choose Better Treatment, Study Says

Personal KinetiGraph (PKG)

A wearable device called Personal KinetiGraph (PKG) can continuously and objectively monitor motor symptoms in people with Parkinson’s disease, which can help clinicians select the most appropriate management therapy and assess treatment impact, a study finds.

The study, “Objective Data in Parkinson’s Disease: A Description of Over 27,000 Parkinson’s Symptom Scores Across the World Using the Personal KinetiGraph® (PKG®),” was presented as a scientific poster during the 2019 American Academy of Neurology’s (AAN) Annual Meeting in Philadelphia.

The PKG system, developed by Global Kinetics Corporation, is a wrist-worn movement recording device that collects data on the person’s motor symptoms, including tremors, slowness of movement (bradykinesia), and abnormal involuntary movements (dyskinesia).

The technology also assesses patients’ daytime somnolence (sleepiness), studies their likelihood for developing impulsive behaviors, and provides information on medication compliance, motor fluctuations, and immobility.

The device has been cleared by the U.S. Food and Drug Administration (FDA), and holds CE certification, meaning it meets EU safety, health and environmental protection requirements.

Previous validation studies have correlated PKG objective scores with other standard Parkinson’s scales, like the Unified Parkinson’s Disease Rating Scale (UPDRS). However, there still is no consensus about the indications for PKG and which patients should wear the device.

To learn more, researchers studied 27,834 complete PKGs — with any identifying data removed — recorded worldwide between January 2012 and March 2018.

Analysis showed 54% of patients had uncontrolled, but likely treatable, slowness of movement, while 10% had uncontrolled, but also likely treatable, dyskinesia. Individuals who used their PKG device regularly had their PKG scores improve, meaning their symptoms became more controllable. That suggests the technology may help to improve clinical decisions, and consequently disease management.

Data from another study, “An Observational Study of PKG Movement Recording System Use in Routine Clinical Care of Patients with Parkinson’s Disease,” was presented in April at the 2019 Parkinson Study Group (PSG) Annual Meeting. That data showed that using Global Kinetics’ technology improved dialogue with patients in more than half of the cases, and enhanced clinicians’ ability to assess treatment impact.

“At Global Kinetics, we are committed to serving the Parkinson’s disease community and providing access to our PKG, which can provide objective measurement in the clinical care setting and help optimize care in this neurodegenerative disease. These presentations underscore the value of PKG in providing valuable information about Parkinson’s movement symptoms and allowing neurologists and movement disorder specialists to have more meaningful conversations with their patients, which translates to optimized care,” John Schellhorn, CEO of Global Kinetics Corporation, said in a press release.

More than 40,000 patient PKG reports have been recorded so far, which has helped more than 200 Parkinson’s specialist clinics to adjust treatment choice and improve management for their patients, according to the release.

Global Kinetics now is enrolling participants in APPRISE, a prospective, multi-center, controlled trial (NCT03741920) designed to evaluate the utility of PKG movement recording system data in the clinical management of Parkinson’s disease in routine clinical care.

Researchers believe PKG recording positively influences clinical decisions, enabling better disease control. In APPRISE, treatment changes with or without the use of PKG data will be evaluated. Participants will have to wear the device for 90 days. Scientists plan to enroll 438 participants across 10 U.S. Movement Disorder clinics. Enrollment is by invitation only.

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Pilot Project Tests Wrist Device That Monitors Symptoms at Home

wearable technology

A pilot project in the United Kingdom is testing a wrist device that is worn like a watch, called Personal Kinetigraph (PKG), to help Parkinson’s patients and their specialist healthcare providers to monitor their condition at home.

The PKG, developed by Global Kinetics, will be tested in the “Developing Home-based Parkinson’s Care” project, led by researchers at the University of Plymouth and University Hospitals Plymouth NHS Trust (UHPNT).

The wearable technology monitors patients’ motor symptoms, using a proprietary algorithm to process the data. Participants also are asked about their non-motor symptoms, including changes in mood, to supplement the movement data delivered by the PKG.

Patients will wear the device for six-day stints, during which their care team will identify and implement necessary treatment changes. The specialist Parkinson’s team will work remotely to ensure necessary help — calls or clinical appointments — is offered when needed.

In the U.K., current guidelines recommend that Parkinson’s patients see a specialist every six months, no matter the stage of their condition. Care is usually provided by a consultant and community Parkinson’s disease nurse specialist (PDNS).

However, results from a recent survey showed that almost half of these appointments (46%) are delayed by more than six months. In 60% of the cases, patients can go an entire year without an appointment. Some regions of the U.K. don’t have the specialist service, and 50% of vacant PDNS positions are due to long-term sick leave or resignation, the audit showed.

“The UK prevalence of Parkinson’s disease will increase by a fifth by 2025, so the challenges associated with providing a timely and patient-centered service will also be much higher,” Camille Carroll, the project leader and an associate professor at the University of Plymouth’s Institute of Translational and Stratified Medicine (ITSMed), said in a press release.

“The existing service puts a lot of pressure on nurses, and attending clinics is arduous for both patient and carer as it presents logistical and physical challenges that add to burden and distress,” said Carroll, also a consultant neurologist at UHPNT.

“We want to help people with Parkinson’s to live the best lives they can for as long as they can, and this project aims to empower patients to take control of their own condition,” she added.

The project will start with 150 patients from Plymouth city, West Devon and East Cornwall.

“The new project is designed to reduce the burden of attending hospital clinics; improve motor and non-motor Parkinson’s symptoms; ensure appropriate and timely contacts to health-care services; and result in improved quality of life for people with Parkinson’s and their carers,” Carroll said.

“If successful, the intervention will prove a means of providing a resilient and sustainable service faced with the future demands of a condition that is increasing in prevalence and complexity,” she added.

The project also will bring together both clinicians and caretakers by providing “co-design workshops” to ensure that patients’ needs and expectations are assessed and met.

A Parkinson’s patient from Looe who is enrolled in the project is pleased with the device’s ease of use.

“Using the PKG is simple and gives the specialist an easy and quick way of monitoring my Parkinson’s disease remotely. Hopefully the new service design will make life easier for others like myself living with the condition,” John Whipps said.

“One of the hardest things with Parkinson’s is trying to decide when your Partner needs their extra doses of medication. The PKG results help take the guesswork out of that, which is really valuable for ensuring the best care possible,” said Sue Whipps, his wife and caregiver.

The pilot project is being delivered in partnership with the Cure Parkinson’s Trust, Flourish Workplace, Sheffield Hallam University, Global Kinetics Corporation, Parkinson’s UK, Fre-est, Radboud University, the South West Academic Health Science Network (SWAHSN) and UCB Pharma.

It’s been funded with £75,000 ($97,619) from the Health Foundation and £15,500 ($27,176) from a Parkinson’s UK Excellence Network Service Improvement Grant.

“The PKG is an exciting example of how technology has the potential to transform care in conditions like Parkinson’s,” said Julie Dodd, director of Digital Transformation at Parkinson’s UK.

“People tell us that one of the most frustrating things about the condition is how unpredictable it is, no two days are the same, which makes it incredibly hard to plan,” Dodd added.

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Study Assessing Smartphone Technology to Track Parkinson’s Motor Symptoms, Researchers Report

smartphone technology

Researchers are conducting a study assessing the use of different motion-tracking sensors to remotely gather data from Parkinson’s disease patients.

The technology holds the potential to noninvasively monitor Parkinson’s motor symptoms, as well as the effects of medication, over the course of patients’ normal daily lives at home.

The study, “Identification of Motor Symptoms Related to Parkinson Disease Using Motion-Tracking Sensors at Home (KÄVELI): Protocol for an Observational Case-Control Study,” was published in JMIR Research Protocols.

Parkinson’s motor symptoms are usually assessed using the motor part of the Movement Disorders Society — Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). This rating scale requires patients to perform a series of repetitive movements, which are then rated by a clinician from zero (normal) to four (severe) to reflect a patient’s level of motor impairment.

However, this scoring method is not sensitive enough and is dependent on an individual clinician’s observations, making it somewhat subjective and prone to variability.

“The symptoms present during the clinic appointment may not reveal all of the issues that are present at home, and the ability to cope independently may vary substantially between the on and off states,” the researchers wrote.

Antiparkinsonian medications can help control Parkinson’s motor symptoms (on periods), but as the disease progresses, patients typically need to gradually increase the treatment dose for maximum benefit. Even after increasing the dose, they might sometimes experience a reappearance or worsening of symptoms (off periods) due to the diminishing effects of the therapy.

There is an urgent need for developing objective, effective, and convenient measurements to help clinicians accurately identify Parkinson’s motor symptoms.

Besides allowing for the collection of quantifiable data regarding the progression of disease-related symptoms, wearable sensors enable remote monitoring of the patient.

This kind of technology may assist clinicians in recognizing on/off periods, helping them to adjust medication doses and schedule to prevent unexpected worsening of symptoms.

Investigators at Tampere University in Finland designed an observational, prospective, case-control study (NCT03366558), called KÄVELI, to help them find new methods to identify and categorize disease-related motor symptoms.

During the study, patients must wear accelerometers connected to the wrist and sensors built into a mobile phone worn on a belt. Long-term motion tracking measurements are acquired at home while patients are going about their everyday lives.

Scientists want to see if motor symptoms related to different stages of Parkinson’s disease can be identified using motion tracking sensors and if the time at which the antiparkinsonian medicine is taken can be detected from the movement signals.

Movement data collection started a year ago, but participant recruitment is continuing throughout spring of this year.

Researchers plan to enroll 50 early-stage Parkinson’s disease (no abnormal involuntary movements, known as dyskinesia, and no on/off state changes), 50 patients in the later stage of the disease (with dyskinesia and on/off state changes), and 50 healthy individuals used as controls. In 2018, the researchers managed to enrolled 103 people, 66 of whom were diagnosed with Parkinson’s.

Patients first have to complete a telephone screening and visit to the hospital. Background characteristics and disease stage is evaluated in the hospital using UPDRS questionnaires and a standardized 20-step walking test.

Before the walking test, a Movesense smart sensor is attached to the nondominant wrist. In addition, the participant wears a smartphone that has a built-in accelerometer, gyroscope (a device that uses Earth’s gravity to help determine orientation), and phone orientation sensor. Patients must also wear a Forciot smart insole, so that scientists can measure the forces applied on the feet. Based on the questionnaires and walking test study, the physiotherapist classifies the participant into one of the study groups.

After this, participants must wear the smartphone at home for three consecutive days. Due to technical requirements, wrist and insole sensors are only used in the 20-step walking test. The motion-tracking system is not worn during sleep or while showering or swimming.

During the three-day period, the participant records the time at which all Parkinson’s disease medications are taken in a smartphone app, as well as in a paper diary format.

“This manual recording was added, since the patients were having problems using the medication registration button despite the simple user interface. The double registration process ensures that medication intake is recorded as accurately as possible. The subjects also record other events, such as falls and other adverse effects, and feedback in the diary,” the researchers said.

“This study will provide quantitative information on PD [Parkinson’s disease] motor symptoms and their statistical properties. The collected dataset will be used to develop algorithms and create tools for remote monitoring of PD progression by physicians and to assist with adjusting the medication,” they concluded.

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Patients Who Respond to L-DOPA Treatment May Have Dyskinesia Earlier Than Those Who Don’t, Study Finds

L-DOPA study

People with Parkinson’s disease whose motor symptoms are eased by levodopa (L-DOPA) therapy may be “more likely” to develop earlier in their disease course the abnormal involuntary movements known as dyskinesia than do patients with a limited response to this treatment, researchers report.

Data on this finding were presented March 30 at the 14th International Conference on Alzheimer’s & Parkinson’s Diseases (AD/PD 2019) in Lisbon. The research, “Variation in the L-DOPA Response in the Parkinson’s Progression Markers Initiative (PPMI) Cohort,” was part of the conference’s Symposium 52: Clinical Aspects & Therapeutic Strategies in PD.

A precise clinical diagnosis of Parkinson’s disease can be difficult in its early stages. Diagnostic criteria include the response of key motor features to levodopa (L-DOPA challenge test).

Physicians rate patient’s motor symptoms according to the motor part of the Unified Parkinson’s Disease Rating Scale (UPDRS part 3) both before and after a “single‐shot” administration of L-DOPA. If a patient’s symptoms improve while taking the medication, he or she is likely to have Parkinson’s.

However, there’s no consensus on how much the levodopa response can vary and still be considered “a response” to treatment.

Researchers at the Institute of Neuroscience and Psychology set up to quantify L-DOPA responsiveness in early Parkinson’s disease and assess its relationship with motor complications. They did so by using the Parkinson’s Progression Markers Initiative (PPMI) dataset.

PPMI was launched in 2010 by the Michael J. Fox Foundation to create a large bank of samples and data from Parkinson’s patients available to the research community. The initiative’s main goal is to identify biomarkers of Parkinson’s disease, a critical next step in the development of new and better treatments for the neurodegenerative disease.

Investigators analyzed the Movement Disorder Society (MDS)-UPDRS scores of 182 patients (69.2% men, mean age at diagnosis 62.1), before and after an L-DOPA challenge test (usual morning dose). The challenge took place 3.5 years after they were diagnosed.

An L-DOPA response of 24.5% or more was considered to be definite, while any percentage below that established threshold was taken as a limited response.

Half of the study sample had a definite levodopa response (median improvement 40.7%), while the remaining half had a limited one (median improvement 11.1%).

Around 14% of the definite L-DOPA responders had dyskinesia, which was significantly more common than in these patients than in those with a limited response (1.1% of cases).

Other motor differences were also evident between these groups: motor fluctuations were observed in 31.1% of patients with a definite response, and in 20.9% of limited responders; uncontrollable muscle contractions (dystonia) were seen in 13.3% of definite versus 5.5% of limited responders. However, differences here did not reach statistical significance.

Definite responders’ levodopa equivalent daily dose was no different than limited responders, the researchers observed.

They concluded: “Only half of early PD patients have a definite L-dopa motor response on challenge testing. Patients with a definite L-DOPA response are more likely to develop early dyskinesia than those with a limited response.”

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High-frequency Brain Stimulation Is Superior for Parkinson’s Patients, Study Suggests

rTMS

Repetitive transcranial magnetic stimulation (rTMS), given at high or low frequency, effectively reduces motor symptoms in Parkinson’s disease patients, but the effects of high-frequency rTMS are superior and last longer, a clinical trial shows.

Investigators also found that the treatment is more effective in patients with akinetic-rigid Parkinson’s — those with slow movements and rigidity — than in patients with the tremor-dominant form of the disease.

The Effect of 20 Hz versus 1 Hz Repetitive Transcranial Magnetic Stimulation on Motor Dysfunction in Parkinson’s Disease: Which Is More Beneficial?” was published in The Journal of Parkinson’s Disease.

The use of non-invasive therapies that stimulate the brain and help treat the symptoms of Parkinson’s disease is an alternative to pharmacologic treatments. For example, rTMS uses electromagnetic currents to stimulate specific regions of the brain. This approach has been shown to ease motor symptoms in Parkinson’s patients.

The therapy can be administered at different frequencies — a varying number of stimuli in the same period of time — which might have different effects. However, it is not clear which frequency yields better results.

Aiming to address that, researchers at Egypt’s Assiut University conducted a clinical trial (NCT03342846) comparing the effects of rTMS either at high (20 Hz) or low (1 Hz) frequency on the motor symptoms of 52 Parkinson’s patients.

Patients were randomly assigned to one of the two groups. Both groups received a total of 2,000 pulses, delivered at the primary motor cortex in both brain hemispheres every day for 10 days, either at a frequency of 20 Hz or 1 Hz.

The researchers measured the motor symptoms using the Unified Parkinson’s Disease Rating Scale part III (UPDRS) and looked for differences before the treatment, after the last session, and one month after the end of the treatment as a primary outcome.

Secondary outcomes included changes in the Instrumental Activity of Daily Living (IADL), a self-assessment score, and a measure of cortical excitability.

The treatment improved the scores of both groups in all scales, but the effects were slightly better in the high-frequency group. Additionally, after one month, high-frequency patients still showed significantly better scores than before the treatment, while low-frequency patients showed no difference.

“It was interesting to note that in the total group analysis, the immediate effects of both 1 Hz and 20 Hz rTMS were similar, but that the effect at 1-month follow-up was only maintained after 20 Hz rTMS,” researchers said.

Regarding cortical excitability, they said that “20Hz rTMS increased excitability as measured by the larger response to single TMS pulses, while there was a tendency for excitability to be reduced after 1Hz rTMS.”

The researchers also performed an exploratory analysis to examine whether the therapy was more effective in patients with akinetic-rigid or tremor-dominant Parkinson’s disease.

“The data suggested that akinetic-rigid patients benefit from 20 Hz treatment whereas there was no significant effect on the tremor-dominant form. Treatment with 1 Hz rTMS had no significant effect on either group,” investigators stated.

They concluded that “20 Hz rTMS over [the primary motor cortex] may be superior to 1 Hz rTMS, particularly in patients with predominantly akinetic-rigid symptoms.” However, studies with a larger number of participants should validate these results.

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ConnectedLife, Ocean Protocol Team to Safely Share Patients’ Motor Symptom Data with Scientists and Doctors

patient data

With the goal of advancing Parkinson’s disease (PD) diagnosis and therapy by securely and safely sharing patient-produced data, the healthcare artificial intelligence (AI) company ConnectedLife is partnering with the technology platform Ocean Protocol.

The collaboration marries the Internet of Things (IoT) — connected devices able to communicate with each other — with deep learning technology, a subset of machine learning whereby artificial neural networks learn from data. The result allows ConnectedLife, based in Singapore, to constantly gather motion data allowing it to objectively monitor patients’ motor symptoms.

Thousands of minutes of “free-living” motion data are being collected from patients in clinical trials with the National Neuroscience Institute in Singapore, as well as from investigation affiliates in Turkey and Germany. At length, the processed raw data becomes a predictive model to discern motor issues in PD.

Ocean Protocol technology works to ensure safe and secure data sharing. When it comes to patient data, research, and disorder management, privacy issues have often offset advances in IoT. Ocean Protocol states that its technology is able to address such concerns.

Collected high-resolution motion and biomedical data are shared through Ocean Protocol to help physicians prescribe optimal therapies and dosages. Machine learning is also expected to facilitate the development of diagnostic tools to detect disease in early states.

”We are enthusiastic about solving significant challenges in healthcare using AI,” Franz M.J. Pfister, MD, ConnectedLife’s chief medical officer, said in a press release. “But, health data is locked up and not being shared due to concerns around control, privacy and security. Removing these roadblocks can help billions of chronic disease patients through AI-enabled prevention, early diagnosis, and personalized treatment that ultimately improves patient outcomes and quality of life.”

Ocean Protocol co-founder Trent McConaghy said his company’s technology will ultimately permit algorithms and models to reach patient data, undergo training, and safely exit with no data exposure.

”With way more data, the accuracy of AI models can be significantly improved to solve real-world problems like decreasing the prevalence of chronic diseases through early diagnosis,” McConaghy said. “It’s a pleasure to work with ConnectedLife to make this a reality.”

ConnectedLife employs IoT sensors and deep learning technology to facilitate early diagnosis and monitoring of chronic diseases like Parkinson’s. Using blockchain technology, Ocean Protocol specializes in safely connecting data providers and consumers.

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Study Cites Factors Associated With Sleep Benefit In Parkinson’s Disease

sleep study

Parkinson’s patients who have had the disease for a long time, who do not sleep very efficiently, and have higher motor impairment are more likely to experience sleep benefit — the phenomenon in which Parkinson’s patients wake up feeling better before taking medication.

The study with that finding, “The related factors of sleep benefit in Parkinson’s disease: A systematic review and meta-analysis,” was published recently in PLOS One.

Sleep benefit is, as the investigators wrote, “a fascinating, but mysterious phenomenon.” It is reported to happen in between a third and half of Parkinson’s patients.

The phenomenon is essentially when a person wakes up from sleep and feels better, with fewer disease symptoms. This is particularly puzzling for clinicians because, at least in theory, just waking up is often when a person has no medications helping them along. So, what could cause sleep benefit?

Researchers still are not sure. Some reports suggest that, although patients may report feeling better, they do not actually perform better on objective motor control tests. aAs such, it might all be psychological.

Still, the team wondered whether patient characteristics — from age and sex to sleep patterns and disease score — might predict which patients would experience sleep benefit.

After a search of the existing scientific literature, the investigators identified seven studies reporting on sleep benefit that included more than 1,300 Parkinson’s disease patients. Using the data from these studies, the authors looked for statistical trends to see which patient traits might be associated with experiencing sleep benefit.

Most of the factors they looked at, including sex, age at diagnosis, and sleep length, did not have a significant association with sleep benefit. However, the investigators did identify three factors that were predictive of experiencing sleep benefit: having had Parkinson’s for a long time; having a low sleep efficiency; and having a high score on the MDS-UPDRS-Ⅲ, a scale used to assess the severity of Parkinson’s motor symptoms, while on medication.

These results might let researchers determine which patients are most likely to experience sleep benefit, though what causes this phenomenon is still pretty much unknown.

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Gut Bacteria Composition Linked to Parkinson’s Disease Severity, Study Shows

gut bacteria composition

The composition of intestinal bacteria in patients with Parkinson’s disease is correlated with disease severity and a worse prognosis, a study has found.

The study, “Gut microbiota are related to Parkinson’s disease and clinical phenotype,” was published in Movement Disorders.

Parkinson’s disease is a chronic and progressive neurodegenerative disorder, caused by the gradual loss of dopamine-producing neurons in the substantia nigra, a region of the brain responsible for movement control. Although the condition is mostly associated with motor symptoms, such as tremors, body rigidity, and balance instability, patients may also experience a series of non-motor symptoms.

Gastrointestinal problems, in particular constipation, are some of the most common non-motor symptoms of Parkinson’s. They are estimated to affect up to 80 percent of all patients and can occur years before the onset of the first motor symptoms.

Previous studies have shown that gut bacteria involved in the regulation of intestinal transit interact with the nervous system, “influencing brain activity, behavior, as well as levels of neurotransmitter receptors and neurotrophic factors,” according to the study. However, the impact of intestinal bacteria in neurological disorders, such as Parkinson’s disease, had never been investigated.

“Based on the early gastrointestinal involvement in PD [Parkinson’s disease] and the vast potential of microbiome-host interactions, we … hypothesized that the fecal microbiome of PD patients differs from that of matched control subjects in terms of bacterial diversity,” the researchers wrote.

To test this hypothesis, the University of Helsinki researchers compared the composition of intestinal bacteria found in stool samples from 72 patients with Parkinson’s disease and 72 healthy controls by genetic sequencing.

Data from the observational study (NCT01536769) revealed that patients with Parkinson’s had a 77.6% reduction in the amount of bacteria belonging to the Prevotellaceae family compared with controls. This family of bacteria, which includes the Prevotella genus, is a group of nonharmful bacteria that live in the colon and help break down complex foods.

“Our findings indicate that the Prevotella associated gut microbiome enterotype [bacteria that live in the intestine] could be underrepresented among PD patients. Investigating whether high abundance of Prevotellaceae has protective effects against PD or whether low abundance is rather an indicator of disturbed mucosal barrier function will be important,” the investigators wrote.

Interestingly, the amount of bacteria from the Enterobacteriaceae family was much higher in patients with postural instability and gait difficulty than in those with tremor-dominant (TD) symptoms. This family of bacteria includes several pathogens, such as Escherichia coli, and other species of harmless bacteria.

“In comparison with TD patients, patients with a non-TD phenotype progress faster [and] have a worse prognosis. Our results suggest that this may be associated with higher abundance of Enterobacteriaceae in the fecal microbiome of non-TD patients,” the researchers wrote.

“Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and PD and the suitability of the microbiome as a biomarker,” they added.

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Exercise That Motivates Parkinson’s Patients to Push Limits Can Offer Range of Benefits, Experts Say

exercise in Parkinson's

With a treatment not yet within reach that might slow the progression of Parkinson’s disease, much less offer a cure, many — doctors, patients, and researchers alike — are looking to exercise in hopes of fending off a worsening of symptoms.

Interest in exercise-based interventions has risen so much that “the number of publications on exercise studies has increased by a factor of 10 since 2000,” Tanya Simuni, MD, chief of Movement Disorders in the Department of Neurology at Northwestern University, said in a 2016 interview on the International Parkinson and Movement Disorder Society website.

Many consider it common sense that exercise can help to compensate for the motor symptoms that mark Parkinson’s — and research points to this possibility — yet scientists still have few clues as to how exactly it does so.

Work done through the Parkinson’s Outcome Project, an ongoing study involving more than 12,000 patients in five countries, suggests that patients should exercise at least 2.5 hours each week to slow decline and maintain a better quality of life. A similar study advised that patients should begin regular exercise at diagnosis.

Still, this research stops short of recommending a specific exercise regimen as a best strategy.

This has led several enterprises — both for-profit companies and nonprofit groups —  to offer classes ranging from dancing to Parkinson’s-only boxing, and products such as specialized at-home exercise equipment that promise to reduce, reverse, and delay symptoms.

While the literature on exercise in Parkinson’s is “extensive,” Rebecca Gilbert, MD, PhD, chief scientific officer of the American Parkinson’s Disease Association and a practicing neurologist, told Parkinson’s News Today, studies on its effects are typically small. Only recently have they begun to grow in size and in quality — but “translating [their findings] into practical recommendations” is a challenge.

Exercise and the brain

In Parkinson’s, neurons in a brain area called the substantia nigra that are responsible for producing a neurotransmitter called dopamine gradually die off, leading to motor symptoms such as tremor and bradykinesia (slow movement).

Levodopa — which works to increase dopamine levels in the brain but cannot rescue damaged neurons — is currently the front-line treatment for the disease.

Some evidence suggests that, like levodopa, exercise may exert some of its effects by increasing dopamine. A recent study of 17 Parkinson’s patients used positron emission tomography (PET) scans of the brain before and after stationary cycling. Results showed that habitual exercisers in this group — eight patients who exercised more than three hours a week — had higher dopamine levels in the dorsal striatum (the brain area that receives dopamine input from the substantia nigra to help control movement) after stationary cycling than the nine others who were sedentary.

The eight exercisers also performed better on functional tests assessing motor symptoms, including the Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 — which measures items such as gait and time to stand — and in tests of non-motor symptoms such as apathy and depression.

Exercise might also go a step further than levodopa by increasing brain-derived-neurotrophic-factor (BDNF), which promotes the survival of neurons that make dopamine — the same neurons that degenerate in Parkinson’s patients.

An analysis of 12 studies of BDNF levels in Parkinson’s patients found lower levels of BDNF in patients’ serum than in healthy individuals (mean difference of 2.99 ng/mL).

Two of these studies showed that patients who completed exercise programs lasting four, eight, or 12 weeks increased both serum levels of BDNF and UPDRS motor scores.

A separate review of 32 studies related to exercise’s effects on BDNF suggested that aerobic exercise increased BDNF serum levels in healthy people. This was seen to be both an acute effect of a single exercise session and a result of consistent exercise. Strength training did not impact BDNF.

Another Phase 2 study (NCT01506479) divided 128 recently diagnosed patients into three groups that either continued not exercising, participated in 30 minutes of gentle treadmill walking four times a week, or were assigned to six months of high-intensity treadmill exercises for 30 minutes four times a week. Those who did the high-intensity workout maintained the same UPDRS motor score at the study’s end as they had at its start, while those in group that did not exercise saw their scores drop by three points, and those who exercised minimally had a two-point drop.

Rock Steady Boxing

Rock Steady Boxing, a nonprofit, non-combat boxing program designed exclusively for Parkinson’s patients, aims to help all — regardless of skill level — take advantage of the benefits of exercise, while building a supportive and understanding community of patients.

Parkinson’s News Today columnist Jean Mellano, an athlete who not only boxes with Rock Steady but also does physical therapy, yoga, weight training, and daily walking to help treat her Parkinson’s, said “the camaraderie is off the charts.”

Joyce Johnson, Rock Steady’s executive director echoed that sentiment, noting “the magic of Rock Steady is the camaraderie and the fact that all of our boxers are fighting back against same disease.”

Founded in 2006, Rock Steady Boxing has grown in popularity and now operates out of more than 700 locations worldwide.

“We’ve actually had neurologists write Rock Steady Boxing on their little prescription pad and sent them to a location,” Johnson said.

Rock Steady allows affiliates to operate for a small fee in boxing gyms, YMCAs, hospitals, and churches. Some programs are free to patients thanks to grants, but most require participants to pay fees similar to that of an average exercise program.

A typical 90-minute class begins with a warm-up, followed by varied exercises designed to mitigate Parkinson’s symptoms through balance and flexibility work, jumping rope, weightlifting, and, of course, boxing.

A case study, listed on the group’s website and published in the journal Physical Therapyof six Rock Steady boxers showed that after 24-36 classes over the course of 12 weeks, all six boxers improved in at least five out of 12 outcome measures, such as the Functional Reach Test, gait speed, cadence, stride length, step width, and other measures of UPDRS part 3, as well as the Parkinson Disease Quality of Life Scale, an assessment of non-motor symptoms. Patients in earlier disease stages did better at 12 weeks, but those with more advanced disease gained benefits with regular classes that ran for 24 and 36 weeks.

Stephanie Combs-Miller, PhD, the case series’ lead author and an associate professor at the Krannert School of Physical Therapy at the University of Indianapolis, published a slightly larger study in 2013 comparing Rock Steady Boxing with a community-based exercise program that included stretching, resistance, aerobic, and balance-based exercises in 31 patients.

Patients again took part in 24-36 sessions of either workout over the course of 12 weeks. The researchers expected that both programs would lead to improvements, but that the boxers’ improvements would be more dramatic than those of patients in the traditional exercise program.

However, Combs-Miller and her team concluded that “both groups demonstrated significant improvements with the balance, mobility, and quality of life,” supporting the idea that any group-based exercise can help Parkinson’s patients, provided they do it consistently.

Still, as Johnson put it: “How much more fun is that for a grandpa to tell his grandkids that he’s going to boxing instead of saying he’s going to therapy?” 

Theracycle and forced exercise

Rock Steady boxers are encouraged by coaches and peers to attempt moves and workout intensities that seem to push the limits of their abilities.

The Theracycle takes this idea a step further, using a motor that forces patients to pedal the stationary bike faster than they could on their own, theoretically maximizing workout effects.

Jay Alberts, PhD, a biomedical engineer at the Cleveland Clinic and an avid cyclist, went on a 200-mile trip in 2003 on a tandem bike with a friend, who also happened to be a Parkinson’s patient. The friend was forced to pedal at Alberts’ pace, which was about 30 revolutions per minute faster than she would have been able to pedal on her own.  According to Alberts, her tremors disappeared during the ride and for a period of time afterward. 

Alberts brought another patient on his tandem bike and noticed similarly striking results. 

But requiring a strong cyclist to take patients out on tandem bike rides regularly is not a practical treatment plan for 10 million patients worldwide.

The Theracycle, a motorized stationary bicycle based on the exercycle invented in 1932, gives patients a safe way to engage in forced exercise — exercise where, in this case, a motor helps them pedal at a speed they wouldn’t be able to reach on their own — at home without a tandem bike or partner.

Alberts conducted a small study in 2009 at the Cleveland Clinic, which appears on the Theracycle website and was published in the journal Neurorehabilitation and Neural Repair, comparing the effects of forced exercise and voluntary exercise (in which patients choose the intensity at which they exercise) on Parkinson’s symptoms.

Ten patients were randomly assigned to complete three one-hour sessions per week of either voluntary cycling or forced exercise using a motorized cycle. After eight weeks, both groups showed improved aerobic capacity, but only the forced exercise group showed improvements (an average of 35%) on the UPDRS part 3.

Mike Studer, president and co-owner of Northwest Rehabilitation Associates, has been using the Theracycle in his Oregon physical therapy clinic since the company reached out to him more than eight years ago, shortly after the Cleveland Clinic study was published. He said he “remained skeptical” of the new research at first, but that the Theracycle “meets and exceeds” expectations.

His clinic also offers the Rock Steady Boxing program, yoga, treadmills, underwater exercises, and more. Studer says “a repetition is not equal to every other repetition.” With the Theracycle, he can control the intensity of a patient’s workout, a crucial factor in its effectiveness.

The main drawback of the machine is its price. It’s not covered by Medicare, and Rich Blumenthal, chief operating officer of Theracycle, admits that the $3,700-$5,900 price tag (depending on the model) can make the equipment difficult to sell. But patients’ lives “are just better when they start using this,” he says.

Both regimens have one thing in common — pushing patients to do more than they may think they are capable of doing.

“There is nothing wrong with people’s bodies. What’s wrong is that neurologically they quit producing dopamine,” Johnson said.

Whether they are encouraged by coaches or by motors, patients often end up doing more than they ever thought they could.

We may never know which exercise regimen is the most effective for preventing Parkinson’s decline, or which is better for any given patients.

“It’s virtually impossible to imagine testing every single modality versus every other modality,” Gilbert said, but “the answer is it’s probably a little of everything.”

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Dopamine Depletion Not Associated with Non-motor Symptoms in Key Parkinson’s Brain Area, Study Shows

dopamine, Parkinson's, non-motor symptoms

Dopamine depletion in a brain region called the striatum does not correlate with the severity of non-motor symptoms in patients with Parkinson’s disease, according to a new imaging study.

The research, “Lack of association between dopamine transporter loss and non-motor symptoms in patients with Parkinson’s disease: a detailed PET analysis of 12 striatal subregions,” was published in the journal Neurological Sciences.

Loss of dopamine-producing neurons in a brain area called substantia nigra and reduced release of this neurotransmitter in the striatum —  a brain region that plays a critical role in motor and reward systems, as well as several aspects of cognition — leads to the development of hallmark Parkinson’s motor symptoms.

Abnormal accumulation of misfolded alpha-synuclein protein further leads to progressive loss of neurons.

In contrast to motor manifestations, the link between dopaminergic deficits in the striatum and Parkinson’s diverse non-motor symptoms — that may include sleep disturbances, constipation, depression, pain, fatigue, urinary difficulty or dementia — is still controversial.

To address this gap, researchers used an imaging technique called positron emission tomography (PET) with a radioligand (a radioactive-labeled chemical compound) to investigate the correlation between non-motor symptoms and dopaminergic deficits in 12 subregions of the striatum.

The scientists used diverse scales for symptoms that included depression, anxiety, fatigue, sleep quality, global cognition and executive function, which comprises goal-directed actions and adaptive responses.

The study included a total of 41 Parkinson’s patients (53.7% men, mean age 67.5 years, mean disease duration 2.3 years). Activity of the dopamine transporter (DAT) protein — responsible for the uptake of dopamine into neurons — and dopamine concentration were calculated in each subregion of the striatum.

“To the best of our knowledge, this study was performed with the most segmentalized subdivisions of the striatum as well as the most numerous nonmotor symptoms,” researchers wrote.

Motor symptoms were evaluated using the Unified Parkinson’s Disease Rating Scale-part III, cognitive function with the Montreal cognitive assessment, and executive function with the frontal assessment battery. The Beck depression inventory, Beck anxiety inventory, Parkinson’s disease sleep scale, fatigue scale, and non-motor symptoms scale (NMSS) also were used.

The results showed that the higher the dopamine depletion in all striatal subregions, the greater the severity of motor complications. As for non-motor symptoms, a simple statistical correlation revealed that depression was associated with dopamine depletion in the left anterior putamen (AP), bilateral posterior caudate nucleus (PC), posterior putamen (PP), and ventral putamen (VP); anxiety was linked with the left posterior putamen and VP; sleep disturbances were associated with the left anterior caudate nucleus (AC), bilateral PC, and bilateral PP; and the NMSS score correlated with left AC and ventral striatum, and bilateral PC, AP, PP and VP. Cognitive function and fatigue did not correlate with any striatal subregion.

However, upon using a more complex statistical method (multiple linear regression analysis) to determine which specific parameter might be independently associated with dopaminergic depletion of striatum, the team found that dopaminergic depletion in all 12 subregions was not related to any of the non-motor symptoms. In contrast, dopaminergic deficit in the right AP and PP were associated with motor symptoms’ severity.

“Striatal dopaminergic depletion was not significantly correlated with any of the various non-motor symptoms in [Parkinson’s],” researchers wrote.

Noting that a prospective study with more participants is required to confirm the findings and that dopaminergic medications may have affected non-motor symptoms, scientists added that the findings suggest that “non-dopaminergic systems are significantly implicated in the pathogenesis of non-motor symptoms in patients with [Parkinson’s].”

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