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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Freezing of Gait Linked to More Severe Disability, Advanced Disease in Parkinson’s Study

gait and Parkinson's

Freezing of gait — the description for a Parkinson’s symptom in which a person’s feet become briefly “glued to the floor,” preventing forward movement despite an intention to walk — is associated with more severe disease and worse motor and non-motor disability, a study reports.

The study, “Factors associated with freezing of gait in patients with Parkinson’s disease,” was published in Neurological Sciences.

Such freezing, a form of akinesia or abnormal movement, while walking is estimated to affect about 50 percent of Parkinson’s patient in later, more advanced, disease stages. Freezing of gait (FOG) is a well-known cause of falls, and a loss of independence and lower quality of life in these patients, but can be difficult for clinicians to assess and treat.

“FOG measurement is quite challenging as objective FOG assessment requires a continuous ambulatory system that can monitor locomotion and FOG episodes,” the researchers wrote.

Studies have suggested that FOG is related to an array of contributing factors, including longer disease duration, more severe disability, wearing off of levodopa treatment, and urinary plus cardiovascular symptoms.

Given this variety, scientists at the Chonnam National University Hospital in Gwangju, South Korea, wanted to estimate the prevalence of FOG and pinpoint factors that could independently contribute to its occurrence in a population of Parkinson’s patients.

A total of 157 patients (ages 62 to 77) were recruited. All “had a positive response to levodopa and did not have clinically significant brain lesions, as seen by magnetic resonance imaging,” tje researchers wrote.

Patients’ age at symptom onset, disease duration, and past plus current medications were all evaluated.

A series of scales/questionnaires were used to assess distinct domains:

Results showed that 70.7 percent — 111 of 157 — of examined patients had FOG.

Researchers reported that “patients with FOG were older [mean age of 71.1], had long disease duration, were taking higher doses of dopaminergic agents, and had higher motor and non-motor scores than those without FOG.” Higher scores mean greater disability.

Among non-motor symptoms, those affecting the cardiovascular, gastrointestinal and urinary systems were more frequent in patients with FOG than in those without. In accordance, cardiovascular, gastrointestinal, urinary and miscellaneous NMSS domain scores were significantly higher in patients with FOG.

Results showed that higher mHYS and UPDRS part II scores — the section of the scale that refers to motor experiences in daily living — and NMSS total scores were significant predictors of  greater freezing of gait severity and frequency.

Evidence indicates that non-motor symptoms like anxiety, fatigue, and pain impact mobility in PD patients, but this study found no difference between mood/cognition scores in patients with and without FOG.

The cause or mechanism of action for freezing of gait in Parkinson’s patients “remains unclear,” the study concluded. But its researchers saw  possible association between FOG and both motor and non-motor disabilities. They suggest that physicians “consider the non-motor features, the motor, and activities of daily living states of the patients for the proper management of FOG.”

And they recommended further studies “to fully assess the role of non-motor symptoms in the mechanism of action during FOG.”

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PKG-Watch Helps in Managing Parkinson’s Symptoms and Lowering Patient Costs, Global Kinetics Reports

wearable monitoring device

Global Kinetics recently announced that the use of its wearable device, Personal KinetiGraph ­­(PKG)-Watch, significantly improves the assessment and management of Parkinson’s disease symptoms, while reducing patients’ costs.

These results were presented in four scientific posters at the International Congress of Parkinson’s Disease and Movement Disorders, held Oct. 5-9 in Hong Kong.

The PKG-Watch is a wrist-worn device that collects data on a patient’s movement, providing information regarding motor symptoms of Parkinson’s — such as tremor, slow or involuntary movements, motor-skills fluctuations, and immobility — to the patient’s doctor.

The PKG system is now commercialized for clinical use in 17 countries, including the U.S. and several European countries. Earlier this year, the company announced that the PKG-Watch was recommended by two separate expert panels to improve clinical management of Parkinson’s disease.

A previous population study using a database of more than 10,000 Parkinson’s patients worldwide who wore the PKG-Watch showed that this technology had the potential to provide clinicians with a passive and continuous assessment of patients’ symptoms, helping them  to better understand disease progression and to optimize treatments.

The study, “Objective Data in Parkinson’s Disease: A description of over 20,000 Parkinson’s symptom scores across the world using the Personal KinetiGraph (PKG),” showed updated results from that growing database, involving 21,234 PKG-Watch users worldwide from 2012 to 2018.

Data supported previous findings, showing that a substantial proportion of patients have suboptimal management of their motor symptoms, with high levels of slowness of movement, tremors, and daytime immobility.

Among these patients, 54% had uncontrolled but likely treatable slowed movement, and 10% had uncontrolled but likely treatable involuntary movements.

Subsequent use of the PKG-Watch significantly improved patients’ motor symptoms, suggesting that the data collected and provided did help clinicians to optimize treatment and improve motor symptom management.

Similar results were presented in the poster “Personal KinetiGraph™ Movement Recording System: An Assessment of Utility in a Movement Disorder Clinic,” regarding an open-label study that involved 28 Parkinson’s patients wearing the PKG-Watch.

The study also showed that patients reported the device had a positive impact on their care, assessing their daily activity levels (96% of patients), providing data that helped to manage their disease (93%) and they could not otherwise provide to their physician (89%), and explaining symptoms (79%).

Another study, titled “Costs and outcomes for Parkinson’s disease patients who have their management adjusted by Personal KinetiGraph (PKG),” assessed the potential cost savings for 33 Parkinson’s patients in Northern Tasmania, Australia, whose oral therapy was adjusted with guidance from the PKG-Watch.

Better disease management associated with the use of PKG-Watch contributed to an estimated annual cost savings of AU$1,719.42 per patient, results showed.

The study, “Pilot economic evaluation of Personal KinetiGraph (PKG) for management of Parkinson’s disease in Australia,” also supported PKG-Watch use being tied to cost savings.

It showed that even small additional therapeutic benefits associated with PKG-Watch contribute to lesser resource utilization and lower cost, compared to current usual care. The study estimated that PKG-Watch use contributed to an annual savings of AU$962 per patient.

“We are pleased to share this data, as well as having our PKG device be used as an objective measurement tool in the clinical care setting,” John Schellhorn, Global Kinetics’s CEO, said in a press release.

“We are also excited that our PKG smartwatch is being used in multiple clinical studies conducted by pharmaceutical and biotechnology companies to evaluate potential new therapies,” Schellhorn added.

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Benefits of Exercise for Parkinson’s Patients Linked to Increased Dopamine Release, Study Suggests

exercise and Parkinson's

Engaging in regular exercise can help preserve the motor and non-motor function of Parkinson’s disease patients, most likely as a result of an increased release of dopamine in the brain, a small study suggests.

The study, “Habitual Exercisers Versus Sedentary Subjects With Parkinson’s Disease: Multimodal PET and fMRI Study,” was published in the journal Movement Disorders.

Exercise has been shown to ease both motor and non-motor symptoms of Parkinson’s disease, including bradykinesia (slowness of movement) and balance, as well as cognition and mood.

While the mechanisms underlying these benefits are largely unknown, researchers hypothesize that exercise may enhance dopamine release. The progressive degeneration and death of nerve cells in the brain that produce dopamine, called dopaminergic neurons, is one of the underlying causes of Parkinson’s disease.

In this study, researchers investigated how dopamine release and other clinical features of Parkinson’s disease differ between patients who exercise and those who remain sedentary.

A total of 17 patients with mild to moderate Parkinson’s disease were recruited, eight of whom engaged in regular exercise at least three times a week for more than three hours total, while nine were sedentary.

All patients underwent two positron emission tomography (PET) scans, one before and one after exercising on a stationary cycle, to determine whether exercise affects the release of natural dopamine in the dorsal striatum — a region of the brain involved in the control of movement. PET scans were performed after overnight withdrawal from dopaminergic medication.

Additionally, participants underwent functional magnetic resonance imaging (MRI) of the brain during a monetary reward task that required randomly selecting one of four cards.

“Subjects were explicitly informed about the probability of obtaining a monetary reward ($0.50) for selecting a winning card during each block. Subjects were also instructed that the task was purely chance (analogous to a slot machine), and there was no pattern to learn that could improve odds,” the researchers wrote.

However, for each selected card, subjects were provided visual (happy or sad face) and auditory (cheers or sighs) feedback, which could alter the card selection process, even though the success of each trial was by chance.

This test allowed researchers to evaluate possible behavioral differences in card selection between groups. Specifically, researchers measured the response of the brain’s ventral striatum, a region involved in the evaluation of rewards.

Participants also completed other tests to evaluate motor and non-motor function, including the Beck Depression Inventory to assess depression and the Starkstein Apathy Scale to measure apathy.

Results showed that habitual exercisers had an increased release of dopamine compared with sedentary patients. They also had greater activation of ventral striatum during the MRI reward task. Their apathy and bradykinesia scores were also lower than sedentary patients.

These results suggest that exercise is associated with improved motor and non-motor functions in Parkinson’s patients, which is likely linked to exercise-enhanced dopamine release.

“Although it appears that exercise plays a role in the clinical outcome of subjects with PD, future randomized control trials are needed to determine the cause-effect relationship between exercise and enhanced DA [dopamine] release, response to anticipation of reward, and clinical outcomes,” the researchers wrote.

“Future studies should also investigate other potential mechanisms of benefit from exercise,” they added.

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Middle-Onset Parkinson’s Linked to Impaired Ability to Detect Emotions, Study Finds

detection of emotions

Patients with middle-onset Parkinson’s disease have difficulties recognizing negative and neutral emotions, deficits that appear to be even stronger in female patients, a study shows.

The study, “Emotion-Specific Affective Theory of Mind Impairment in Parkinson’s Disease,” was published in the journal Scientific Reports.

Parkinson’s disease is known to affect the frontal-subcortical circuit, an area responsible for motor and behavioral processes.

This region is also responsible for processing the theory of mind (ToM), a complex function that enables the detection and recognition of cognitive and emotional states (thoughts, feelings, beliefs, intentions, or desires) of other people, and thus the anticipation and interpretation of their behaviors. These abilities are crucial in a social situation for successful communication.

ToM can be divided into cognitive ToM, involved in reading the cognitive beliefs of other people, and affective ToM, involved in recognizing and interpreting the emotional states of others.

While Parkinson’s disease is known to impair cognitive ToM, whether it influences affective ToM remains controversial, with several studies reaching varying conclusions.

Researchers in Taiwan evaluated whether affective ToM is affected in Parkinson’s patients with either young-onset (YOPD) or middle-onset (MOPD) disease, and whether impaired affective ToM is associated with Parkinson’s motor symptoms.

Researchers first recruited 30 people with middle-onset Parkinson’s, 30 young-onset Parkinson’s patients, and 30 healthy participants. Young-onset was defined as developing the disease at 49 years of age or younger, while middle-onset was classified as developing the disease between 50 and 70 years old.

Affective ToM was assessed through the validated Reading the Mind in the Eyes Test (RMET), which comprises 36 black-and-white photographs of pairs of eyes that each depict a particular emotion. These photographs are shown to the participant, who must pick the adjective that best fits the emotion.

Results showed that while young-onset Parkinson’s patients and healthy individuals appeared to have comparable abilities to infer emotions in others (similar RMET scores), patients with middle-onset Parkinson’s had significant difficulties recognizing emotions — particularly negative and neutral emotions.

Researchers also found that these deficits were only present in women in the middle-onset group.

“This finding may imply that female patients with MOPD have a vulnerable emotional recognition ability; thus, early detection and appropriate treatment are needed for the female MOPD population,” the researchers wrote.

They noted that these results may explain the variability of previous studies, since Parkinson’s patients with particular disease onsets or genders showed distinct differences in affective ToM.

Next, the team analyzed the data of 107 middle-onset Parkinson’s patients, which included the initial 30 patients, plus an additional 77 participants, to better understand the potential associations between deficits in affective ToM and Parkinson’s motor and non-motor symptoms in these patients.

In this Parkinson’s population, the ability to accurately interpret the emotional state of others decreased with disease duration and with the presence of specific motor symptoms, such as slowness of movement, walking and posture instability, and impaired speech and facial expression.

Additional analysis showed that impaired ability to recognize others’ emotions in these patients was associated with the development of motor symptoms, but not of non-motor symptoms. The same was true for women in this group of patients.

The team noted that the data support an association between affective ToM and motor symptoms, and that additional studies are required to clarify the underlying mechanisms of this link, and to more thoroughly evaluate the potential link between affective ToM and cognitive function.

They also believe the use of a test with both verbal and nonverbal information to assess affective ToM may “provide more comprehensive context that mimics real-life situations.”

“Whether the affective ToM can be used as a biomarker to detect or diagnose PD [Parkinson’s disease] is a noteworthy issue, and the development of a useful diagnostic tool is therefore needed,” they concluded.

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Facial Expressions in Parkinson’s Patients Mirror Asymmetry Seen in Motor Symptoms, Study Says

facial expressions

Although no marked differences in the asymmetry of facial expressions distinguished Parkinson’s disease patients and healthy individuals in a study, patients most clearly expressed an emotional reaction on the side of the face corresponding to the side of the body less affected by Parkinson’s motor symptoms, a study found.

Its researchers concluded patients’ facial asymmetry when displaying emotions is a consequence of general motor symptom asymmetry, rather than difficulties or problems in processing emotions.

The study, “Emotional facedness in Parkinson’s disease,” was published in the Journal of Neurotransmission.

Parkinson’s is characterized by the gradual loss of muscle control and lack of facial expression, sometimes accompanied by cognitive deficits.

Previous studies have suggested that hemispheric dominance — a phenomenon in which one side of the brain is more important than the other for a given function — in emotional processing can lead to an asymmetric facial expression.

Although Parkinson’s motor symptoms tend to be rather asymmetric (i.e., more pronounced on one side of the body), studies had not addressed facial and emotional asymmetry in Parkinson’s patients.

A research team in London and Italy explored the relationship between motor symptom asymmetry and facial expressiveness in Parkinson’s disease.

The study enrolled 20 patients and 20 healthy people serving as controls, who were video-recorded while displaying facial expressions: one that was neutral, and six basic emotions (anger, disgust, fear, happiness, sadness, and surprise).

The most expressive pictures obtained from the video-recordings were then cut down the middle and put through a program to generate ‘chimeric’ faces that showed only the right side of the face (right side manipulated to make full face) and the left side (a left-left combination). Investigators then asked nine healthy people with no prior connection to the study to rate which one of the two chimeric faces looked more expressive. Raters’ choices, reaction times, and confidence levels were recorded.

To evaluate a possible link between facial expressiveness and motor symptom asymmetry, researchers performed correlation analysis between the global facial laterality index (pooling all emotions together) as well as for the indexes of each emotion separately, and the body laterality index (defined by the side of the body most affected by Parkinson’s symptoms).

No substantial differences were found in how the nine raters judged emotional expressiveness on the two chimeric faces (right-right and left-left), whether within the Parkinson’s and the control group, or between the two groups.

In Parkinson’s patients, however, investigators found a correlation between the global facial laterality index and the body laterality index, suggesting that each patient’s most expressive side of the face corresponded to the body side less affected by Parkinson’s symptom’s.

“Despite the lack of significant facial asymmetry in PD [Parkinson’s disease] and healthy subjects, the relationship we found between the intensity of facial expression and motor symptom lateralization supports the hypothesis that there is some facial asymmetry of emotional expression in PD which relates to the general lateralisation of the motor features of the disorder rather than a specific abnormality in emotional processing,” the researchers wrote.

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Parkinson’s Study Analyzes Levodopa‐induced Dyskinesia’s Effect on Sleep

sleep study

When a person is awake, brain circuit activity is constantly “on.” This activity needs to be normalized during sleep. Researchers now report that neuronal activity in Parkinson’s disease patients with levodopa-induced dyskinesia fails to decrease during sleep.

The study, “Levodopa-induced dyskinesia in Parkinson’s disease: sleep matters,” was published in Annals of Neurology.

The brain’s structure and functional networks are constantly changing/evolving in a biological process scientists call “neuronal plasticity,” which affects the brain’s learning and memory abilities.

Levodopa (L-Dopa), one of the main therapies used to treat Parkinson’s symptoms, “successfully controls motor symptoms for several years and then induces motor fluctuation and abnormal involuntary movements, i.e. levodopa-induced dyskinesias (LIDs),” researchers wrote.

This long-term, therapy-related complication results in important functional disability, often requiring complex pharmacological or surgical interventions.

Although LDIs are believed to be associated with changes in neuronal plasticity in the striatum — a brain area involved in multiple aspects of cognition — studies have demonstrated abnormal motor cortex plasticity in LID patients. The motor cortex is the brain area involved in the planning, control, and execution of voluntary movements.

In addition, changes in cortical slow wave activity (SWA) — the major characteristic of deep sleep key for both cortical restructuring and functioning, which, in turn, supports cognition — have been described in animal models of Parkinson’s disease with LID.

SWA increases with wake duration, peaks in early sleep, and declines in late sleep. Animal studies have shown that “rodents exposed to combined levodopa treatment and sleep deprivation developed earlier and more severe LID than animals that were not sleep deprived,” authors noted.

The team at Neurocenter of Southern Switzerland investigated if sleep could influence clinical presentation of Parkinson’s in humans, as previously observed in animals.

A total of 27 Parkinson’s patients (50-65 years old) were divided into three groups:

  • de novo: seven recently diagnosed patients who had received only azilect (rasagiline, by Teva) as dopaminergic therapy;
  • advanced: nine subjects without LID using their usual therapy, but demonstrating the end-of-dose or wearing-off phenomenon;
  • dyskinetic: 11 advanced patients with LID.

Seven healthy and age-matched participants also were recruited as controls.

Researchers evaluated subjects’ mood and sleep complaints as well as their Parkinson’s motor symptoms, using a series of rating scales, and asked them to maintain regular sleep-wake schedules.

A wristwatch-like device was attached to individuals’ non-dominant wrist to monitor their sleep/wake cycles for one week. This method is known as actigraphy. Because of technical failure, one patient from each of the Parkinson’s groups could not undergo rest/activity cycles monitoring.

Additionally, participants were submitted to whole night video polysomnography-high-density electroencephalogram (EEG) recording, meaning those studied had their brain waves, blood oxygen level, heart rate, breathing patterns, eye and leg movements monitored while they were asleep. Recording data was corrupted by artifacts in two de novo patients and one dyskinetic participant, and as a result was excluded from the SWA analysis.

Subjects were followed for at least six months.

Results showed there was a decline in SWA in the de novo, advanced and control groups, but not in dyskinetic patients, who had their SWA persistently elevated during the night.

In accordance, all groups except the dyskinetic one, manifested a significant decrease in SWA between early and late sleep, further supporting the investigators’ hypothesis that dyskinetic patients have their much-needed overnight brain activity normalization process compromised.

In all Parkinson’s patients, total sleep time and sleep efficiency were negatively correlated with disease duration, which is consistent with previous studies.

However, “while the correlation between [deep sleep] and disease duration was positive in both [de novo and advanced] patients, it was surprisingly negative in [dyskinetic] patients,” researchers wrote.

A possible explanation is there may be biological compensatory mechanisms in the de novo and advanced sample that can be compromised in the dyskinetic one, making dyskinetic patients unable to sleep efficiently as disease progresses.

Because levodopa dose influences dyskinesia onset, investigators performed a correlation analysis between sleep parameters and levodopa-equivaled daily dose.

A negative correlation of total sleep time and sleep efficiency with levodopa-equivalent daily dose was observed in all patients with motor fluctuations, i.e., in both advanced and dyskinetic groups. Importantly, slow wave (or deep) sleep was negatively correlated with levodopa-equivalent daily dose only in patients  experiencing LID.

“In conclusion, these results support our preclinical findings of a clear association between sleep and LID at the electrophysiological, behavioral, and biochemical levels,” researchers wrote.

“Although our findings do not imply a causative role for the lack of SWA reduction in the emergence of LID … they do suggest an association between sleep and some clinical [features] of PD and suggest a relationship between sleep disruption and LID,” they concluded.

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