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Stopping Trimetazidine May Ease Parkinson’s Symptoms, Improve Quality of Life, Study Says

trimetazidine and Parkinson's symptoms

Discontinuing trimetazidine treatment in people with Parkinson’s disease may lessen their motor and non-motor symptoms and improve their quality of life, a study has found.

The study, “The Impact of Trimetazidine on Disease Severity and Quality of Life in Parkinson’s Disease,” was published in the journal Scientific Reports.

Trimetazidine, which is sold under the brand name Vastarel and also available as a generic, is an antianginal medication used as add-on therapy for treating stable coronary heart disease — conditions that cause a reduction of blood flow to the heart. It is approved for this indication in Europe and other countries but not in the U.S. 

Previous studies have shown trimetazidine to have adverse effects on motor function, including causing reversible parkinsonism, tremor, and orofacial dyskinesia (involuntary repetitive movements of the mouth and face). It can also worsen symptoms of existing movement disorders like Parkinson’s disease.

These effects may be caused by the medication’s piperazine core, a chemical compound also found in antipsychotic medications that have been reported to induce parkinsonism and worsen Parkinson’s symptoms. 

Piperazine is thought to block the action of dopamine receptors, which play an important role in movement regulation. 

Based on previous studies, in 2012, the European Medicines Agency recommended against the administration of trimetazidine to patients with Parkinson’s disease.

However, recent data show that this recommendation is not followed strictly enough, and trimetazidine is still being prescribed to people with movement disorders.

Researchers at University of Pécs in Hungary have now evaluated the impact of trimetazidine treatment on the severity of clinical symptoms and its effects on health-related quality of life in people with Parkinson’s disease. 

The study included 42 patients with Parkinson’s disease, at a mean age of 71.1 years, who had been prescribed trimetazidine. All patients were also taking oral anti-parkinsonian medications.

At the start of the study, patients had been taking trimetazidine for a mean of 6.5 years, at a mean dose of 72.1 mg. Participants underwent detailed neurological and neuropsychological assessments.

Trimetazidine was stopped and patients were again reevaluated three months later. Their oral antiparkinsonian treatment was kept stable until the follow-up.

Results showed significant lessening of Parkinson’s clinical symptoms at follow-up, measured by the Movement Disorder Society-sponsored Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), a four-part assessment of motor and non-motor Parkinson’s symptoms.

Clinically relevant improvements were observed upon discontinuation of trimetazidine according to changes in scores of different parts of the MDS-UPDRS, compared with the beginning of the study: a 25.7% change in part 1, which relates to non-motor experiences of daily living; a 23.8% change in part 2, which assesses motor experiences of daily living; a 28.5% change in part 3, a motor examination that included notable lessening in disturbances of posture, gait (walking) problems, and postural instability; and a 30.1% change in part 4, which also measured motor complications.

Trimetazidine discontinuation also lessened Parkinson’s disease severity in 16 patients (38.1%), including two whose motor symptoms completely disappeared. However, in these two cases, “discontinuation of antiparkinsonian medications resulted in the reemergence of Parkinsonian symptoms,” the researchers wrote.

They also noted an overall lessening of non-motor symptoms, especially sleep problems and depression. 

“The use of [trimetazidine] in patients with [Parkinson’s disease] and the negative impact of the drug on the severity of Parkinsonian symptoms seem to be clinically meaningful problems,” the researchers wrote.

Additionally, patients experienced better health-related quality of life, as measured using the 39-item Parkinson’s Disease Questionnaire, which assesses patient-reported health status and quality of life.

Stopping trimetazidine and using alternative antianginal treatment did not cause any cardiovascular events in these patients up to 12 months of follow-up.

“Our results provide clinical rationale for avoiding the use of [trimetazidine] in [Parkinson’s]. [Trimetazidine] seems to worsen the severity of Parkinsonian symptoms in a clinically meaningful manner and have a negative impact on the [health-related quality of life],” the team wrote. 

“Therefore, discontinuation of the drug in patients with [Parkinson’s] seems to be a clinically adequate therapeutic intervention,” they concluded.

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COVID-19 Infections May Appear as Rapid Worsening of Motor Symptoms

COVID-19 infections report

Infections with the new coronavirus may manifest in people with Parkinson’s as a rapid worsening of disease symptoms, hindering early and accurate diagnosis of infections in this population, according to a case report on two patients.

It also points to a possibility of more severe infections in these patients, but further studies are needed to confirm the prevalence and mortality of COVID-19 cases among those with Parkinson’s.

The correspondence describing these two cases, “Rapid worsening in Parkinson’s disease may hide COVID-19 infection,” was published in the journal Parkinsonism and Related Disorders.

Parkinson’s patients are not more likely to be infected by COVID-19 than the general population, but their older age puts them at risk for more severe infections.

Diagnosing COVID-19 in these patients, however, may be challenged by symptoms that are common to both illnesses, like fatigue, loss of sense of smell, hot flush, and muscle pain.

Currently, little information exists about how COVID-19 presents in Parkinson’s patients, or about outcomes among those infected.

Researchers at the Institut du Cerveau et de la Moëlle épinière in France reported on two people with Parkinson’s who experienced a worsening in their motor symptoms as first evidence of a COVID-19 infection.

The first patient, an 83-year-old man, had been diagnosed with Parkinson’s about 21 years ago and had a deep brain stimulation (DBS) device to help control his motor symptoms. An outpatient at the institute, he showed a worsening in motor function, with falls, postural instability, as well as speech, chewing and swallowing difficulties. Five days later, fever and cough also appeared.

He was diagnosed with COVID-19 and hospitalized with signs of moderate pneumonia. While there, his motor and respiratory symptoms stabilized for three days. But he then developed acute respiratory distress syndrome, a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs, and died within a few hours.

A similar disease course was seen in the second patient, a 73-year-old woman with a 23-year history of Parkinson’s who also had a DBS device. The woman was admitted to the hospital due to sudden falls and speech problems that had started two days earlier. She had no fever, or respiratory or digestive symptoms.

At admission, the patient was confused and her Parkinson’s symptoms appeared to be more severe than usual. But a brain CT scan was normal and her DBS was functioning properly. Due to an elevation in inflammation markers, she underwent chest imaging scans, which revealed a mild pneumonia. COVID-19 infection was then confirmed.

The woman increased her levodopa dose, but her symptoms remained severe. After 10 days in the hospital, she also developed acute respiratory distress syndrome and died in a few hours.

“Those two cases illustrate that early and accurate diagnosis of COVID-19 in PD [Parkinson’s disease] patients may be challenging [since] COVID-19 may mimic PD evolution,” the researchers wrote.

This overlap can be particularly difficult during a home quarantine, because added stress and reduced physical activity alone can worsen Parkinson’s symptoms, they added.

“This study draws attention to the potential severity of COVID-19 in PD and highlights the need of larger studies to assess the exact prevalence and fatality rate of COVID-19 in PD population,” the team concluded.

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Duloxetine in Trial Fails to Ease Pain, But May Help with Motor Skills

duloxetine and Parkinson's

Use of duloxetine, a treatment for depression and nerve pain, fails to alleviate pain in people with Parkinson’s disease, according to data from a clinical trial.

However, results also showed that it may be of benefit in easing motor symptoms and improving patients’ quality of life, although more studies are necessary.

The findings, “A double-blind, randomized controlled trial of duloxetine for pain inParkinson’s disease,” were published in the Journal of Neurological Sciences.

A neurodegenerative disorder, Parkinson’s is characterized by the gradual loss of dopaminergic neurons in the substantia nigra — a region of the brain responsible for movement control — together with brain inflammation.

Previous studies have shown that patients have a lower pain threshold, possibly due to imbalances in the levels of several neurotransmitters — chemicals that allow nerve cells to communicate — in the brain.

Duloxetine, marketed as Cymbalta and Irenka, is normally prescribed to treat depression and to ease pain in individuals with chronic pain disorders like fibromyalgia, or pain caused by nerve damage. The medication works by preventing certain neurotransmitters from being taken up by nerve cells in the brain, including those thought to be involved in pain processing in people with Parkinson’s.

“Reports on duloxetine’s effect on pain in patients with Parkinson’s disease, however, are rare. One study reported that levels of pain … were significantly lower after 6 weeks of treatment with duloxetine … among the 20 people who completed the study,” the researchers wrote.

Given this study’s small number of patients and its open-label design (lacking a placebo group for comparison), its findings are susceptible to bias.

A team of researchers in Japan, for this reason, carried out a randomized, double-blind, and placebo-controlled trial to evaluate duloxetine’s effectiveness at treating pain in people with Parkinson’s.

The trial (jRCTs061180028) enrolled 46 patients recruited at the Ehime University Hospital, and ran from May 2015 to September 2019. All patients were at the early progressive stages of Parkinson’s, and experienced mild to distressing pain.

Participants were randomly assigned to duloxetine or a placebo, both given orally. The process of randomization took into account patients’ age and pain intensity levels, which were assessed using the Visual Analogue Scale (VAS) for pain.

For the first two weeks, patients were given a duloxetine capsule (20 mg) or placebo capsule every day. Then, for eight weeks, they took two capsules of either duloxetine (total 40 mg dose) or a placebo daily. In the study’s last two weeks, participants went back to one 20 mg capsule of duloxetine or a placebo every day.

Other medications used by patients were maintained, unless “change was necessary”.

The study’s main goal was to assess changes in pain intensity levels from the study’s beginning (baseline measures) to week 10, using the VAS.

Exploratory outcomes included changes in the progression of motor symptoms (Unified Parkinson’s Disease Rating Scale Part III, UPDRS-III), depression (Beck’s Depression Inventory, BDI), and patients’ quality of life (Parkinson’s Disease Questionnaire-39, PDQ-39).

Nine of the 46 enrolled failed to complete the study, including seven — all in the duloxetine group — who discontinued due to adverse events.

No significant differences in pain intensity were found between people treated with duloxetine or those given a placebo through week 10.

However, duloxetine-treated patients experienced significant improvements in their UPDRS-III scores — which translates to a lessening of motor symptoms — and in three areas of the PDQ-39 (activities of daily living, emotional well-being, and communication) compared to those given a placebo.

“These results may indicate that duloxetine has beneficial effects on PD [Parkinson’s disease] patients in more ways than simply through its anti-depressant effects,” the researchers wrote.

“[W]e were unable to confirm previous reports suggesting a favorable effect of duloxetine on pain. Nevertheless, the results are informative, as they pertain to the second study of duloxetine for pain in Parkinson’s disease and the first … placebo-controlled clinical trial using duloxetine to Parkinson’s disease,” they added.

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Parkinson’s Symptoms May Help to Judge Ability to Do Daily Tasks

motor skills

The clinical symptoms experienced by people with Parkinson’s disease, like dyskinesia or postural instability, may help to distinguish and group patients whose ability to perform daily activities are more or less affected, a new study suggests.

These findings were detailed in, “Can We Predict the Motor Performance of Patients With Parkinson’s Disease Based on Their Symptomatology?,” a study published in Frontiers in Bioengineering and Biotechnology.

Parkinson’s is characterized by motor symptoms like tremor, slowness of movement (bradykinesia), uncontrolled involuntary movement (dyskinesia), and postural instability, as well as by non-motor symptoms like sleep problems and cognitive decline.

These symptoms affect to differing degrees a person’s ability to go about activities of daily life. But currently there is no way of knowing how a person’s symptoms, taken together, correlate with an ability to perform daily tasks requiring motor skills.

To investigate this, researchers at the Université de Sherbrooke, in Canada, assessed symptoms and motor performance in a group of 115 Parkinson’s patients, mean age of 67, without psychosis and who could walk without assistance. A group of 69 elderly individuals without this disease, matched by age and sex, served as controls.

At examination, patients were asked to take their regular medication and were equipped with a suit containing 17 sensors to objectively measure their motor symptoms.

All were then asked to perform three motor tasks: rising from a chair, walking, turning, sitting down (the Timed-Up and Go, or TUG, test), eating soup, and inserting pins into a board using both hands, alternately, for 30 seconds (the Purdue Pegboard test). They also answered a questionnaires providing socio-demographic data, as well as information about their cognitive health and quality of life.

Based on patients’ performance on the three motor tasks, researchers broke them into four groups: those within normal range for all tasks (group 1), those whose fine motor skills (or dexterity) were slightly affected (group 2), those mainly affected on the TUG test (suggesting limited mobility; group 3), and patients affected in all these activities (group 4).

Notably, some symptoms and medications were significantly different among groups, including postural instability, dyskinesia, bradykinesia, rigidity, freezing of gait, and the use of amantadine (marketed as Gocovri, among other brand names).

An increase in postural instability was found to be linked to a four to nine times greater likelihood of poor performance in the TUG test or in all activities (assignment to groups 3 or 4), the researchers reported. Low-to-moderate dyskinesia increased the chances of being in the normal group (relative to the groups 2 or 3, those slightly affected in fine motor tasks or mainly affected during TUG).

Higher levels of rigidity increased the likelihood of being affected in all activities (group 4).

Amantadine as part of a treatment regimen was seen to lower the risk of being in the group 3 (limited mobility).

The model showed a good accuracy overall, being able to place 76% of patients in their correct motor group based solely on their symptoms and medication. But researchers suggest that the grouping of patients according to their motor performance on tests could be further refined; the soup eating test, for instance, was not seen to be relevant in this classification.

Still, “this study demonstrated that it is possible to predict the mobility performance of any patient, based on personal clinical features,” the researchers wrote.

“[T]hese results appear promising, and may lead to more personalized treatment by identifying and targeting symptoms that specifically impede a particular patient’s motor performance,” they concluded.

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Levels of Progranulin Protein May Affect Parkinson’s Severity, Progression

possible disease biomarker

Blood levels of progranulin — a protein whose deficiency has been linked to neurodegeneration — may reflect Parkinson’s severity and progression, and serve as a disease biomarker, a recent study suggested.

The research, “Reduced plasma progranulin levels are associated with the severity of Parkinson’s disease,” was published in Neuroscience Letters.

Progranulin is widely distributed throughout the brain. Studies indicate this protein is a potent regulator of neuroinflammation and a promotor of long-term neuronal survival.

Low progranulin levels have been associated with neurodegenerative and lysosomal storage disorders. Blood levels of progranulin are also suggested to be lower than usual in Parkinson’s patients.

But little is known about how blood levels of progranulin and disease severity in Parkinson’s might correlate.

Researchers explored this possibility by measuring progranulin blood concentrations and correlating them with symptom severity.

Their study involved 55 patients (24 men and 31 women, mean age 71.1) and 55 people without the disease serving as controls, (22 men and 33 women, mean age 67.8).

Disease severity was quantified using the Unified Parkinson’s Disease Rating Scale (UPDRS) and the Hoehn and Yahr scale. Patients’ motor symptoms were assessed using the UPDRS motor section (UPDRS-III).

Blood plasma tests revealed that progranulin levels were significantly lower in Parkinson’s patients compared to controls (333.8 vs. 364.2 ng/ml). Blood levels of progranulin were also found to negatively correlate with Parkinson’s severity, motor symptoms, and disease duration.

This means that lower progranulin levels associated with greater disease severity and motor symptoms, and longer disease duration. It also indicates a possible protective role of progranulin against the neurodegeneration process associated with Parkinson’s.

Previous studies have shown that boosting progranulin production protected dopamine-producing neurons from degeneration in mouse models of Parkinson’s, supporting progranulin’s role in better neuronal survival and neuroinflammation control.

“These results indicate that circulating [progranulin] levels might reflect the severity of neuronal loss and might be developed as a potential biomarker of [Parkinson’s disease],” the researchers wrote.

Progranulin deficiency has also been implicated in other neurodegenerative diseases besides Parkinson’s, including frontotemporal dementia, a group of dementias mainly affecting decision-making and behavior or language and speech, depending on the brain area that’s affected.

More research is necessary to investigate the protein’s diagnostic potential in Parkinson’s disease, the researchers advised.

A Phase 1 clinical trial in healthy volunteers (NCT04111666) is expected to test AL101, a therapeutic compound with a potential ability to raise progranulin levels in the brains of people with neurodegenerative diseases. But this study, listed as starting in December 2019, does not yet appear to be enrolling.

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Motion Machine’s Ability to Ease Motor Symptoms in Parkinson’s Entering Trial in Australia

Parkinson's and balance

A trial in Australia will test a motion machine, called the Reviver, to understand whether it can improve balance, mobility and sensory-motor coordination in people with moderate to advanced Parkinson’s disease and atypical parkinsonism.

Exercise has been shown to help ease Parkinson’s symptoms. The Reviver machine, by Isodymanics, is designed to stimulate the vestibular system, the sensory system that provides a sense of balance and information about body position.

The machine works by placing the user at a tilted angle and rotating them in a slow and radial, wave-like motion.

The reaction to being tilted off-balance can induce a brain response that activates muscles across the body, including those that may be dormant as a result of age, infrequent use, damage, or disability. Specifically, it activates nerve pathways that then aid in balance, enhance muscle strength, and help resist the effects of gravity.

Isodynamics reports early evidence suggesting the Reviver’s use can improve mobility and lessen Parkinson’s symptoms, with patients demonstrating a 22% increase in mobility; namely, quicker “up and go” test times over an average of 26 days. This test measures the time it takes for a person to rise from a chair, walk three meters (about 10 feet), turn around and return, then sit down again.

“The anecdotal results with our patients have been very positive,” Geoffrey Redmond, Reviver’s developer, said in a press release. “We’re really glad to see the Reviver being used in a formal trial.”

The trial will assess whether a 12-week program using the Reviver machine improves balance, mobility, and sensory-motor coordination. It plans to enroll 30 patients with moderate to advanced Parkinson’s disease or atypical parkinsonism. People with atypical disease have some evident Parkinson’s symptoms, like muscle stiffness or balance issues, but who do not respond well to standard medications. Their symptoms are caused by other disorders.

The trial is being overseen by Terry O’Brien, a neurologist at Monash University and led by Ben Sinclair, a brain imaging expert at Monash and with Alfred Health. Participants will be required to attend twice weekly sessions for 12 weeks at The Alfred in Melbourne.

Enrolled patients will be split into two groups, based on their diagnoses. One group will undertake the Reviver exercise regime on top of their standard of care, and the second (a control group) will continue with standard of care without using the Reviver.

Those interested in participating or receiving more information about the trial can call Isodynamics at 02-9524-2188 (in Australia, country code +61) or email the company.

“We now need to see what kind of results can be generated during a formal, randomised controlled trial,” Sinclair said.

“It’s an exciting project because people affected by Parkinson’s have a limited range of treatment options. This study provides a rare opportunity to explore and uncover a new possible treatment pathway for people affected by Parkinson’s,” he added.

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Palliative Care Leads to Better Quality of Life than Standard Care for PDRD Patients, Study Finds

Palliative care

Palliative care — focusing on physical, psychosocial and spiritual treatment — for people with Parkinson’s disease and related disorders (PDRD) led to a significantly better quality of life (QoL) than standard care alone, a study finds.

Easing of both non-motor and motor symptom severity was linked to palliative care intervention — and those with the greatest needs benefited the most, the researchers said.

The study, “Comparison of Integrated Outpatient Palliative Care With Standard Care in Patients With Parkinson Disease and Related Disorders,” was published in the Journal of the American Medical Association, Neurology

Parkinson’s disease and related disorders (PDRD) are a group of disorders that share core features of Parkinson’s but have additional symptoms. People with PDRD do not respond well to standard Parkinson’s medications and have a poor prognosis. 

Given the additional needs of patients with PDRD, an increasing number of medical centers are providing palliative care for these patients. 

While such care is typically associated with hospice and cancer, “recognition of the potential relevance of [palliative care] in other contexts has expanded substantially over the past decade to include earlier deployment, delivery to noncancer populations, delivery in outpatient settings, and delivery by persons not specializing in palliative medicine,” the researchers said.

Palliative care, known as PC, aims to improve quality of life (QoL) and reduce suffering by addressing medical symptoms, psychosocial issues, and care planning. 

Despite the recent advances in patient care, few studies are available that support the effectiveness of palliative care in the PDRD population.

Thus, a team of investigators from the University of Colorado (UC), the University of California, San Francisco (UCSF), and the University of Alberta (UA) in Canada, designed a study (NCT02533921) to examine the effects of this care approach. The team compared outpatient palliative care with standard care alone to assess any differences in participants’ QoL, the burden on the caregiver, and other patient-related outcomes. 

A total of 210 PDRD patients with moderate-to-high care needs were enrolled in the study, with participants randomly divided into a standard care group and a palliative care group. Of those selected, 104 patients and 88 caregivers were part of the standard care group, while 106 patients and 87 caregivers were assigned to the palliative care intervention group.

Standard care was provided by the patient’s primary care physician and a neurologist. 

Outpatient palliative care included standard care plus visits every three months either in person or by telemedicine — two-way videoconferencing and advanced information communication technologies. The PC team consisted of a specialized neurologist with palliative care workshop training, a nurse, a social worker, a chaplain experienced with Parkinson’s patients, and a physician specializing in this type of care. 

The primary outcomes were defined as differences in patient QoL after six months, measured using the Quality of Life in Alzheimer’s Disease (QoL-AD) scale, and by determining caregiver burden, using the 12-item Zarit Burden Interview (ZBI-12). 

Additional patient outcomes also were assessed, including symptom burden and health-related QoL. Patient and caregiver mood, grief, spiritual well-being, and overall impression of change also were reported. The outcomes for both patients and caregivers were recorded at the beginning of the study, and every three months for 12 months.

The results showed that, after six months, those receiving outpatient palliative care had significantly better QoL compared with those receiving standard care. When QoL assessments of patients and caregivers were combined, the impact was even greater. 

While the ZBI-12 difference in caregiver burden at six months was not significant, reassessment at 12 months showed a statistically significant difference. 

The greatest benefit from palliative care intervention was seen among the patients who were assessed, at the beginning of the study, as having greater needs. After 12 months, palliative care had a greater effect on women compared with men. 

In comparison with the standard care group, the PC group had a greater number of patients who experienced a clinically significant benefit in QoL-AD, and a lower number of those who scored worse.

Factors such as age, mood, symptom burden, disease severity, and cognition were not significantly different. However, improvements in non-motor symptoms, motor symptoms severity, and caregiver anxiety were linked to palliative care. 

Standard care alone was not favored for any outcome, the results showed. 

“Outpatient PC is associated with benefits among patients with PDRD compared with standard care alone,” the researchers concluded. “This study supports efforts to integrate [palliative care] into PDRD care.”

The researchers said such efforts are particularly needed for people with more severe symptoms.

“The integration of [palliative care] into PDRD care holds the potential to improve outcomes, particularly for persons who are underserved by current models of care (eg, patients with advanced illness and dementia),” the investigators said.

“Because the PC intervention is time-intensive and resource-intensive, future studies should optimize triage tools and consider alternative models of care delivery, such as telemedicine or care navigators, to provide key aspects of the intervention at lower cost,” they recommended. 

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Way of Detecting Parkinson’s Early via Typing Patterns Being Tested and Refined

typing patterns

A type of computational analysis that works to analyze typing patterns may help in detecting motor signs of Parkinson’s disease at early stages, the researchers who developed the analysis report.

This new method, which appeared to allow researchers to discriminate between people with early Parkinson’s and those without the disease, may also speed data collection and analysis of disease states across neurodegenerative ills.

The study, “Classification of Short Time Series in Early Parkinson’s Disease With Deep Learning of Fuzzy Recurrence Plots,” was published in the IEEE/CAA Journal of Automatica Sinica.

Objective measures of Parkinson’s motor signs are crucial for diagnosing the disease early and correctly, as well as for monitoring progression and assessing treatment response. Early detection of Parkinson’s disease (PD) is particularly relevant, as people at early stages of the disease are more likely to benefit from neuroprotective treatments.

“Because a significant amount of the [midbrain’s] substantia nigra neurons have already been lost or impaired before the onset of motor features, people with PD may first start experiencing symptoms later in the course of the disease,” the researchers wrote.

Current methods to evaluate motor symptoms focus on a person’s movements and balance while walking, which requires a trained specialist and clinic visits. As such, they limit the frequency at which disease state and progression is likely to be assessed.

In addition, these methods involve the collection of data “during relatively long walking periods, causing discomfort to the participants or impracticability of performance in clinical settings,” the researchers wrote.

Increasing efforts are being made to develop easier and more accessible methods of detecting Parkinson’s motor signs, including the use of digital technologies.

A previous study showed that analyzing the time a person takes between pressing and releasing a key while typing (key hold time) could be used to detect motor problems in the early stages of Parkinson’s. The analysis involves a computational self-learning algorithm able to generate a Parkinson’s disease motor index based on key hold times.

This approach — which measures key hold times during the normal use of a computer without any change in hardware — was shown to efficiently distinguish people with and without Parkinson’s using data from either a controlled clinic setting or an uncontrolled at-home setting.

While it has the potential to be an objective and user-convenient tool to detect Parkinson’s, this approach “require the time series of length to be considerably long.”

Researchers at Linköping University (LiU), in Sweden, developed a new way of analyzing typing patterns based on a very short time series of data for machine learning (artificial neural networks that learn from data). It intends to avoid discomfort to participants in performing long physical tasks for data recording, and to effectively differentiate Parkinson’s patients from healthy people.

The team used the first short segments of the key hold time data from 43 healthy individuals and 42 Parkinson’s patients (average time since diagnosis, 3.9 years), part of a publicly available database. Of note, patients were on parkinsonian medication, but stopped their treatments for at least the 18 hours before the typing test.

Researchers first translated the data into a set of two-dimensional, grey-scale images of texture, called fuzzy recurrence plots, which were then used for machine learning with an algorithm named long short-term memory (LSTM)-based deep learning.

The use of fuzzy recurrence plots in machine learning allowed for distinguishing among people with and without Parkinson’s using less data than current methods.

According to a press release, researchers believe their findings are “encouraging,” and plan to further explore the use of fuzzy recurrence plots and improve the algorithm to better determine a patient’s disease state.

They also highlighted that this approach may be applied to other types of data, with a goal of improving machine learning and reducing the amount of data required to achieve good results for differentiating healthy people from those with disease.

The research team plans to evaluate this approach against walking and balance data collected from people with Parkinson’s and other neurodegenerative diseases, such as Huntington’s disease and amyotrophic lateral sclerosis (ALS).

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Higher Risk of Falls Linked to Longer Disease Duration and PIDG Subtype, Study Suggests

gene mutation cancer risk

In Parkinson’s patients, the risk of falls increases depending on disease duration and having the postural instability/gait disturbance (PIDG) subtype, but is not signficantly correlated with non-motor symptoms, a study suggests.

The study, titled “Falls in persons with Parkinson’s disease: Do non-motor symptoms matter as much as motor symptoms?,” was published in Arquivos de Neuro-Psiquiatria.

Falls can be a major problem for people with Parkinson’s disease, with some individuals being at greater risk of serious falls. However, identifying a person’s fall risk can be challenging because the risk is affected by a multitude of different factors that may or may not be related to Parkinson’s disease itself.

Intuitively, it may seem that the best predictors of falls are likely related to motor symptoms — after all, falling is associated with moving. But, previous studies have suggested that measurements of motor function aren’t good predictors of falls.

The researchers behind this new study set out to investigate whether including non-motor symptoms, in addition to motor symptoms, would help better predict fall risk in people with Parkinson’s.

To test this, the researchers assessed 179 people (average age of 64.6 years, mean disease duration of 10.4 years) with Parkinson’s who were seen at the National Institute of Neurology and Neurosurgery in Mexico City. The participants’ clinical history, including fall history in the past year, was taken.

Participants underwent a series of evaluations, including disease state using the Hoehn and Yahr scale, assessment of motor symptoms using relevant parts of the Movement Disorders Society Unified Parkinson’s Disease Rating Scale, as well as non-motor symptoms using the Non-Motor Symptoms Scale.

Overall, 16.8% had experienced a fall in the last year, with just over half of these having experienced more than one fall — the average was 2.5 falls per month. The researchers noted that this is a “very low” proportion of patients who experienced falls (“fallers”), which “could partially be explained by under-representation of advanced forms of the disease,” a limitation of the study.

The researchers constructed statistical models using several types of data that they had collected, with the aim of identifying factors that were significantly over-represented among the fallers — thus, being predictive of falling.

They found that the severity of motor and non-motor symptoms in the participants was not significantly linked with fall risk.

However, the study did find two factors that were linked with fall risk: the first was disease duration. Patients who had experienced symptoms for longer were more likely to fall — average disease duration was 12.8 years in the fallers group and 7.4 years in the non-fallers group.

The second risk factor was having the PIDG subtype (which accounted for 59.8% of the participants), one of the three groups into which Parkinson’s patients can be divided based on their most prominent motor symptoms. The PIDG subtype is associated primarily with difficulty standing and/or walking and is thought to be associated with rapid progression of disease and cognitive dysfunction.

While about half (53%) of the people in the non-fall group had the PIDG subtype, nearly all (93%) of those in the fall group had the subtype.

“Disease duration and the PIGD subtype were identified as relevant risk factors for falls in [people with Parkinson’s disease]. Non-motor symptoms appear to have a less important role as risk factors for falls,” the researchers wrote, adding that these findings suggest a need for a “more intensive approach in fall prevention” for people with this subtype.

 

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Devices to Record the Progression of PD

devices

The progression of Parkinson’s disease (PD) is unique to every person, with different early, middle, and late-stage symptoms. However, this view of PD progression may be an artifact of limited data rather than an accurate description. We need new ways of measuring PD symptoms as they change over time. We have the technology to create new devices that people can use over an extended period, across multiple settings and severity of “off periods.”

I see progression as a change in the intensity and duration of “bad” days and off periods. Many longitudinal studies investigate the progression of PD (for example, the rate of progression in exercise), but it is hard to find studies that measure changes in response to treatment. Devices discussed in this column might change that.

Better measurement of PD progression begins with a few assumptions. First, subtle, early motor symptoms will appear before more obvious symptoms, such as tremors or bradykinesia. Second, early motor symptoms will be inconsistent and episodic. Third, we have the technology to build mobile monitoring devices.

I recently read that a patient being evaluated for “internal tremors” showed no signs of tremor during a physical examination of his bare feet. However, once he put his socks and boots on, an astute clinician observed the left bootlace swinging in such a way that, when measured, fit the PD pattern of a tremor. In other words, while the patient didn’t exhibit tremor during a visual examination of his bare feet, his shoelace reflected an underlying tremor!

A shoelace is not going to be a reliable measuring device, but it proves that slight motor changes that are difficult to detect do exist. I’ve designed two possible motor symptom detection devices: a mobile swing monitor (MSM) and a fine motor skills test (FST). Both devices would record and monitor movement fluctuation over time and across settings in daily life over 10 or so days. Both devices use sensors to track and record movement through three dimensions.

The MSM uses five “movement in 3D space” sensors — one on each wrist, one on each ankle, and one on the belt — with recording hardware for all five. Worn for several days, like a Holter monitor, the MSM would map the sway of the arms, legs, and body over time and across settings. The MSM is very similar in appearance to wearable training weights, which can measure the slightest variations in body movement. Wearable training weights are used by Olympic and World Cup judges to evaluate Shaun White’s amazing snowboard flips and twists.

The FST, illustrated in the graphic below, has a 3D monitor in the “soda can” receptor where the block is inserted. Similar to the game “Operation,” the patient must remove objects from openings in the receptor without setting off the buzzer. The warning light goes off when the sensor plate is touched.

The FST will measure how the person adjusts position and control while using fine motor skills. The FST uses a 3D monitor and four independent, pressure-sensitive plates that record when the patient fails to insert the block and when the block is aligned. The plates can be positioned at different widths using an adjustable difficulty setting, making it harder to insert the block without touching the plates.

Fine skills motor test, designed by Dr. C. (Photo by Dr. C)

Data gathered by these two devices may provide patients and medical professionals with more accurate clinical data about motion, tremors, and fine motor skills over a greater period. They could demonstrate the progression of intensity and duration of bad days and off periods and serve as the beginning of a database on PD progression.

Many people are excited about using technology to provide outcome measures. As we know, technology is not being utilized in offices with patients to help understand the progression of PD. But hopefully, that will change.

If these devices are already being tested in the home of PD patients, sign me up!

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

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