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Subtle Alterations in Postural Behavior May Help Diagnose Parkinson’s Earlier

Postural behavior

People with Parkinson’s have postural adjustments even at early stages of the disease when clinical symptoms of postural instability are not evident and despite the use of antiparkinsonian medications, a recent study shows.

Researchers believe these findings suggest that postural behavior may be used as an early indicator to diagnose the disease.

The study, “Postural Behavior in Medicated Parkinson Disease Patients: A Preliminary Study Searching for Indicators to Track Progress,” was published in the Journal of Central Nervous System Disease.

Parkinson’s disease usually is diagnosed based on the presence of classic  motor symptoms. But other signs of the disease are present sometimes years before motor symptoms are evident, though still insufficient to make a definite diagnosis.

Identifying patients in this earlier phase would ensure they receive treatment early, before their disease progresses to more advanced stages and significantly affects daily activities.

Generally, Parkinson’s patients with early disease are classified as not having postural instability. But modern technologies are more sensitive to subtle impairments in balance, and potentially may identify changes in postural behavior that take place even in earlier stages of disease.

To clarify the presence of postural changes in early Parkinson’s disease, and whether these changes can be used to diagnose the disease before motor symptoms are evident, researchers at the Western Michigan University and collaborators at the Federal University of Piauí, Brazil, investigated two groups of Parkinson’s patients, and compared them to a group of healthy controls.

Participants included nine patients with early disease — defined as a Hoehn and Yahr Stage rating scale up to 2, which means their balance was not yet affected — and nine patients with mid- to advanced disease (a Hoehn and Yahr Stage of 2.5 or higher, whose balance was already compromised).

These patients were all taking antiparkisonian medication, allowing researchers to account for the effects of medication on balance, which the team believes is a clear limitation of prior studies that lacked a standardization on this parameter. Controls included nine healthy subjects matched by age, who had no history of sensory, muscular, or neurological disorder.

Participants were asked to perform two simple postural tasks: stand quietly on a force platform with arms crossed, with eyes open or closed. Each task took 120 seconds. During that time, the platform collected information regarding participants’ center of pressure, including body sway trajectory (how the center of pressure moved), sway amplitude (how far in each direction it went), sway velocity (how fast it moved), and sway jerkiness (how shakier body sway was).

The team found that most measures were similar across patients and controls when they did the test with their eyes open. But Parkinson’s patients already showed greater sway velocity and jerkiness compared to controls in this task. Late-stage patients also had more overall sway movement and greater sway amplitude.

When the task was done with eyes closed, patients also had higher sway jerkiness — though sway was only laterally shakier — compared to controls, but not higher sway velocity. Those with advanced disease also had greater sway amplitude.

No significant differences were seen between groups of Parkinson’s patients in either task. Also, while controls and early-stage patients swayed more, faster, and shakier when they stood still with their eyes closed, no differences were seen in advanced patients with eyes open and closed.

The findings show that Parkinson’s patients have alterations in postural behavior starting in early stages of disease, and despite the use of dopaminergic medication. “This finding indicates that balance control is affected even before clinical signs surface,” the researchers wrote.

“Therefore, postural markers used in this study are [of] great importance to improve early diagnosis of postural instability in PD [Parkinson’s disease], record progress of balance control, and assess fall risk. They should also be implemented in clinical trials of pharmacotherapy and balance training protocols specific to populations diagnosed with PD,” they concluded.

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IRL752 Can Safely Manage Treatment-resistant Symptoms in Parkinson’s Dementia, Trial Shows

IRL752, Parkinson's dementia

Treatment with IRLAB Therapeutics‘ small molecule IRL752 is safe and well-tolerated by Parkinson’s disease patients with dementia, and may help manage symptoms that are unresponsive to levodopa, results from a Phase 2a trial show.

In particular, the treatment was found to reduce apathy, improve balance, and decrease the risk of falls. Planning and executive function also seem to improve with IRL752. Notably, no severe adverse events related to treatment were reported.

The study, “A Phase 2a Trial Investigating the Safety and Tolerability of the Novel Cortical Enhancer IRL752 in Parkinson’s Disease Dementia,” was published in Movement Disorders.

IRL752 is a small molecule that has the ability to enhance communications between nerve cells in the frontal cortex, a major brain area that controls cognitive functions. It does so by increasing the availability of two important chemical messengers (neurotransmitters) — norepinephrine and dopamine — and by activating specific genes involved in nerve cell communication.

Both of these chemical messengers are needed for cells to communicate properly but their levels are reduced in those with Parkinson’s disease, leading to the motor and cognitive deficits characteristic of the condition.

After showing that IRL752 is safe and well-tolerated in a group of 40 healthy volunteers included in a Phase 1 trial, with no cardiovascular effects reported, IRLAB designed a Phase 2a trial (2017-001673-17) to evaluate the treatment’s safety, tolerability, and preliminary signs of efficacy in people with Parkinson’s and dementia taking their normal antiparkinsonian medications.

“The aim with IRL752 is to improve balance and reduce the risk of falls in patients with Parkinson’s disease, which is the current top priority within the treatment of Parkinson’s disease,” Joakim Tedroff, MD, PhD, chief medical officer of IRLAB, said in a press release.

The trial included 32 patients, median age of 72 years, from Sweden and Finland who were randomly assigned IRL752 or a placebo. The treatment’s dose was adjusted for each patient during the first 14 days, after which dosing was kept stable for an additional 14 days of treatment. The average dose achieved in the stable dose phase was 600 mg daily.

The trial’s main goal was to determine the safety and efficacy of repeat IRL752 dosing in these patients. Secondary efficacy measures included IRL752’s effects on Parkinson’s symptoms, postural control and walking speed, freezing of gait, cognitive function, neuropsychiatric symptoms, and global function.

During the four-week treatment period, 72% of patients reported at least one treatment-emergent adverse event, 58% of which were possibly related to treatment. Most adverse events were mild, affected the central nervous system, and occurred predominantly in the first two weeks, when the dose was still being adjusted for each patient.

The most common adverse events related to IRL752 included abdominal pain, headache, tremor, increase in liver enzymes (indicating possible liver damage), and cognitive disorder.

Two patients reported severe adverse events during the study, but none were deemed related to treatment. Also, no patient experienced changes in vital signs or in cardiovascular parameters.

Regarding efficacy, patients taking IRL752 showed significant lessening of axial motor symptoms such as postural instability and falls, as well as reductions in apathy and cognitive impairment. These symptoms are known to be largely unresponsive to levodopa treatment.

Notably, “the possible effect of adjunct IRL752 treatment on postural dysfunction seemed not to be a result of a general effect on parkinsonism because none of the other classical hallmark symptoms of Parkinson’s disease were affected by the treatment,” the researchers wrote.

Instead, they believe that an increase in norepinephrine likely explains the improvements, as symptoms such as poor balance and apathy have been associated with lower levels of this neurotransmitter.

The researchers also showed that IRL752 reached concentrations in the blood believed to have a therapeutic effect, suggesting that “IRL752 may be dosed at potentially clinically effective dosing in this patient population.”

The company is now planning a Phase 2b clinical trial to continue evaluating the effects of IRL752 on the frequency of falls in Parkinson’s patients.

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Impaired Backward Walking Linked to Motor Symptoms, Fear of Falling in Early Parkinson’s, Korean Study Suggests

backward walking

Backward walking is significantly impaired and associated with motor symptoms and fear of falling in newly diagnosed Parkinson’s patients, a small Korean study suggests.

These results point to backward walking parameters as potential biomarkers of Parkinson’s disease progression. The researchers called for future studies investigating the dynamics of backward walking in people with Parkinson’s, and its link to falls.

The study, “Backward Gait is Associated with Motor Symptoms and Fear of Falling in Patients with De Novo Parkinson’s Disease,” was published in the Journal of Clinical Neurology.

People with Parkinson’s are at a significant risk of falls due to gait (walking) and balance problems. Specifically, these patients show increased stride-to-stride variability and take shorter and slower steps.

While most gait studies in people with Parkinson’s have focused on walking forward, backward gait has been suggested to be even more impaired in these patients. It’s also been associated with freezing of gait, defined as not being able to start stepping forward, with no apparent cause.

Several studies have also shown that people with Parkinson’s have considerably more difficulties in walking while performing a secondary cognitive task, known as dual-task gait. Dual-tasking measures an individual’s ability to carry out a cognitive task — such as counting, or naming words that start with a particular letter — while engaging in a motor skill like walking.

However, since changes in walking parameters are closely associated with the progression of motor symptoms, most of what is known about walking difficulties in Parkinson’s patients comes from studies preformed in people at advanced stages of the disease.

Thus, understanding gait dynamics and difficulties in early-stage Parkinson’s disease remains largely unknown.

Now, a team of Korean researchers set out to determine which type of gait — forward, backward, or dual-task — was more strongly associated with motor symptoms or the risk of falling in people with de novo Parkinson’s disease, meaning they are newly diagnosed and still untreated.

The study involved 24 individuals with de novo Parkinson’s — 13 men and nine women, who had the disease for less than five years, were between 50 and 75 years old, and were able to perform various types of gaits. An additional 27 unaffected people, including 16 men and 11 women, were used as controls.

Clinical data for all participants was measured through several tests and scales, including the Korean version of the Montreal Cognitive Assessment, the Fear of Falling Measure (FFM) — a rating scale in which lower scores indicate greater fear of falling — and the Unified Parkinson’s Disease Rating Scale part II and III, which assesses motor symptoms.

The participants’ gait parameters were analyzed using the computerized GAITRite system with a 4.6-meters (16 foot) long, pressure-sensitive walkway mat. Each type of gait was tested 10 times while walking at a comfortable speed. Dual-task gait consisted of walking while subtracting serial sevens.

Results showed that de novo Parkinson’s patients had a slower walking speed and shorter stride in all three gaits, compared with unaffected people. However, backward gait showed the highest stride-to-stride variability in both stride time and length.

Dual-task gait also showed significant variability in stride length between the two groups of participants, while forward gait showed no significant differences.

When looking at the potential associations between gait speed, motor symptoms, and fear of falling in these patients, the team found that reduced backward gait speed was significantly associated with a wider range of motor symptoms. These included walking difficulties, bradykinesia (difficulty in body movement), postural instability, and total motor score. These individuals also had an increased fear of falling.

Reduced dual-task gait speed was specifically linked to worse bradykinesia and total motor score, while reduced forward gait speed was associated with reduced tremor score. That was consistent with previous studies suggesting that reduced gait speed is “more pronounced in non-tremor-dominant [Parkinson’s] patients,” the researchers said. None of these gaits’ speeds were associated with fear of falling.

“These results indicate that slow walking with a short stride is a clear feature of de novo PD regardless of the gait task being performed, and the earliest alterations of gait variability may first become apparent in [backward gait], followed by [dual-task gait] and then [forward gait],” the researchers said.

The team added that these findings suggest that backward walking speed is more strongly associated with the risk of falling and is “a potential surrogate marker for the progression of motor symptoms or gait impairment in PD.”

Future studies are required to confirm and better understand the association of backward gait and motor symptoms and to investigate the clinical relevance of stride-to-stride variability in the different types of gaits, the researchers said. They also called for additional studies into the link between backward walking and falls in people with Parkinson’s disease.

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Torso Exercises Helped Reduce Severity of Forward Stoop in Parkinson’s Patients

torso exercises

Torso-specific exercises can help improve posture and balance by significantly reducing the severity of forward stoop in patients with Parkinson’s disease.

The study with that finding, “Four-week trunk-specific exercise program decreases forward trunk flexion in Parkinson’s disease: A single-blinded, randomized controlled trial,” was published in the journal Parkinsonism and Related Disorders.

Forward bending of the spine, known as disease-related forward trunk flexion (FTF), is a common complication observed in patients with Parkinson’s disease. FTF can result in permanent postural imbalance, pain, frequent falls, and irreversible deformities. Early detection and rehabilitation efforts through focused physical therapy can help in reducing pain and delay motor symptoms progression. However, information is limited on FTF rehabilitative efforts in Parkinson’s patients.

In a controlled trial (NCT03741959), researchers assessed the impact of a four-week trunk-specific rehabilitation program in correcting the posture of  37 Parkinson’s patients with FTF. Patients were assigned randomly to the experimental group (19 patients) or the control group (18 patients).

The exercise regimen for the experimental group consisted of three routines. First was a 20-minute session of self-correction exercises in three levels of difficulty to be performed in front of a mirror (visual feedback), while measuring the muscle activity using electromyogram (proprioceptive feedback), or without any feedback. The second routine included 20 minutes of trunk stability exercise and improving muscle strength and coordination. The third set of exercises included functional tasks that were meant to trigger behavior changes to unconsciously correct posture and movement to aid daily activities.

In the four-week program, the exercise regimen was performed in 60-minute sessions for five days a week.

The control group performed 20 minutes of joint movements, exercise for muscle strength, and stretching, followed by gait training and balance exercises.

All the exercise routines were performed under the guidance of a trained physical therapist, and each treatment session consisted of 10 exercises with repetitions based on the patient’s capacity.

In the four-week program, the exercise regimen was 60-minute sessions five days a week.

Patients who underwent the four-week program showed a significant decrease in the degree of forward bend compared to the control group, indicating a positive effect from the trunk-specific exercises. The exercise regimen helped them straighten up by a mean of 9.73 degrees by the end of the program, and 8.84 degrees at the one-month follow-up. In contrast, the control group exercises corrected posture by a mean of only 1.62 degrees and 0.95 degrees at the same time intervals.

“The main findings of the present study are that the four-week trunk-specific exercise program reduced the degrees of FTF in patients with Parkinson’s disease more than the conventional treatment, and the training effects were maintained at one-month post-treatment,” researchers wrote.

Further assessments showed that both groups exhibited significant improvement in patients’ ability to perform daily activities, as determined by the Unified Parkinson’s Disease Rating Scale III (score range 0-132, with higher scores representing worsened symptoms), compared to before the intervention.

Also, significant reduction in pain was reported in both the groups at one month of follow-up. However, there was no statistical difference between the two groups, researchers noted.

The team also assessed the impact of the exercise in improving static balance (ability to balance while standing still) and dynamic balance (ability to balance while moving or switching positions). No difference was noted in both groups immediately after completion of the four-week program. But, at the one-month follow-up, the static and dynamic balance was significantly improved in the experimental group compared with the control group.

In addition, patients in the experimental group reported a marked overall decrease in the number of falls per month at the one-month follow-up, as well as an overall improvement in their health-related quality of life at the one-month follow-up; the control group experienced a decline.

“The four-week trunk-specific rehabilitation training decreased the forward trunk flexion severity and increased postural control in patients with Parkinson’s disease,” researchers stated.

More studies are warranted to further validate these preliminary findings and explore more extensively the potential of torso-specific exercises for Parkinson’s patients, they added.

 

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Wives of Parkinson’s Patients are More Impaired in Postural Stability from Caretaking, Study Finds

postural stability, wives of Parkinson's patients

Wives who take care of husbands with Parkinson’s disease have greater impairments in their stability while standing than housewives or more active women of the same age, a study shows.

The research, “Postural stability in Parkinson’s disease patients’ wives and in elderly women leading different lifestyles,” appeared in the journal Health Care for Women International.

Increased impairment of posture and gait that comes with aging results from alterations in the central nervous system — brain and spinal cord — muscle and joint dysfunction, deteriorated physical capability, and other health issues.

The level of physical activity in the elderly is varied and associated with their lifestyle, responsibilities, and support. While some are able to participate in various forms of physical activity, others spend significant time doing housework or caretaking, and so don’t have opportunities to be physically active.

“This type of activity (housework) certainly is not conducive to the health of the caregivers and some aspects of it can be destructive both physically and mentally,” the study stated.

Parkinson’s patients require permanent care as their movements are unstable and slow. Their caregivers’ own stability may be affected, especially if the patient’s postural balance in impaired, and there’s an increased risk for falls.

“The (Parkinson’s) patient is hunchbacked and leans forward, making rising and sitting difficult,” the researchers wrote.

In the study, Polish researchers compared the postural stability of wives of Parkinson’s patients to that of women doing higher physical activity — students of the University of the Third Age (U3A; adult education movement for retired individuals) — or average physical activity (housewives).

A total of 128 unemployed women were included: 44 were wives of Parkinson’s patients (with a mean age of 66.5 years), 43 were U3A students (68.0 years), and 41 were housewives (65.6 years).

When not housekeeping, the wives of Parkinson’s patients spent their time caring for their husbands and resting. U3A students participated in organized activities twice a week, such as dance, exercises, nordic walking, or swimming. Housewives preferred to spend their time resting passively, which could be watching TV, reading, or chatting with family and friends.

Scientists assessed the women’s balance using a so-called stabilometric platform. Each participant was tested twice for 30 seconds. While one test included complete postural control with eyes open, the second was under conditions that limited postural control, with eyes closed.

The women stood on the platform in a relaxed and upright position, with their upper limbs hanging loosely. They were barefoot and dressed lightly. During the trial with eyes open, the women were asked to focus on a fixed point — a circle with a 15-centimeter diameter and a line through it, which was hanging on the wall three meters away.

No woman had difficulty standing due to neurological, orthopedic, or other issues. An assistant stood behind the participants to prevent falls.

The stability parameters analyzed were the mean velocity of center of pressure (COP) displacement (which measures postural balance); COP velocity in the sagittal plane (the one that divides the body into left and right halves) and frontal plane (front and back); and sway range in sagittal plane — mainly controlled by the ankles — and frontal plane directions, which depends mainly on the control of hip joints. The COP is the point where the sum of all forces on the body act, including gravity.

The wives of Parkinson’s patients were the tallest, and each had a lower body mass index, with none obese, than the other participants. Nearly 30% of housewives and U3A students were overweight.

As for postural balance, the wives of Parkinson’s patients had significantly higher values of mean velocity, displacement velocity, and sway range than housewives and students, which means they had greater impairment in balance. In contrast, U3A students, who engaged in regular organized physical activities, had the slowest velocity and lowest sway.

“It can be thus supposed that engagement in physical activity has positive effect on balance of older adults,” the scientists wrote.

However, the housewives and students showed greater differences in displacement velocity with eyes closed versus open, compared with the wives of patients.

“Surprisingly, compared to the other women, the wives of (Parkinson’s) patients did very well with eyes closed in terms of frontal plane sway,” the researchers said. “This may be the ‘practice effect’ of the long-term strength as well as the motion coordination required for caring for the (Parkinson’s) patients, who are typically characterized by instability.”

“The study results clearly point to the fact that the Parkinson’s disease patients’ wives require support in the form of balance enhancing training,” the team concluded. “Therefore, undertaking any form of physical activity aiming at redressing postural stability deficits would be beneficial for (this) group of women.”

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Vitamin D May Improve Balance in Younger Parkinson’s Patients, Pilot Study Suggests

Short-term supplementation of vitamin D in high doses may improve balance in people with Parkinson’s disease younger than 66, according to results of a Phase 2 pilot study.
The study, “A randomized, controlled pilot study of the effects of vitamin D supplementation on balance in Parkinson’s disease: Does age matter?” was published in Plos One.
Parkinson’s patients are at a high risk of falling mainly due to problems with balance — one of the primary symptoms of the disease. It is estimated that 70 percent of Parkinson’s patients fall at least once a year.
Falls are associated with substantial injury, disability, hospitalization, and reduced quality of life in Parkinson’s patients and in older people in general. However, no pharmaceutical or surgical intervention is currently known to significantly improve balance.
As a result, there is an unmet need to discover or develop therapeutic approaches to improve balance in Parkinson’s patients.
At the same time, individuals with Parkinson’s, particularly those with advanced disease, have lower levels of vitamin D, which is involved not only in bone health, but also in brain function.
Previous studies have shown that vitamin D supplementation reduces fall rates and improves balance in older people. While it has been suggested that higher doses of vitamin D are more effective than lower ones, more recent evidence suggests that higher doses in older populations may have the opposite effect, being associated with more frequent falls and fractures.
A randomized, double-blinded, placebo-controlled Phase 2 pilot study (NCT01119131) evaluated the safety and effectiveness of high-dose vitamin D supplementation on balance, gait, falls, strength, and cognition in Parkinson’s patients. Disease severity and quality of life were also assessed.
Researchers analyzed the data of 51 patients, at a mean age of 66.57 years, who were randomized to receive either a high dose of vitamin D (27 patients) or a placebo (24 patients), in addition to 1,000 mg of calcium, daily for four months.
Balance function was measured using the Sensory Organization Test (SOT), an objective test to measure impairments in postural stability or balance, which has been found to be the most suitable for assessing balance in relation to vitamin D levels.
Results showed that vitamin D supplementation doubled patients’ vitamin D blood levels after four months of treatment, while patients who received placebo showed no substantial changes in their levels.
Patients receiving the high dose of the supplement showed no significant improvements in balance, compared with those in the placebo group. In addition, no significant changes were found for gait, strength, cognition, disease severity, or quality of life between the two groups of patients.
However, when researchers divided the patients who received vitamin D into two age groups — those 66 or younger, and those 67 and older — the supplement was found to significantly improve the balance of patients in the younger group, compared with the older age group. No significant therapeutic effect of the supplement was found for any of the other measures.
High-dose vitamin D supplementation appeared to be safe, with no serious adverse events reported.
These findings highlight the possibility of an “age-dependent role for vitamin

Source: Parkinson's News Today

Parkinson’s Patients with Tendency to Fall Control Balance Differently than Non-Fallers, Study Suggests

Parkinson's fall risk

Parkinson’s disease patients who have a tendency to fall use different strategies to control their balance than those who do not fall, according to a recent study.

The study, “Fallers with Parkinson’s disease exhibit restrictive trunk control during walking,” was published in Gait and Posture.

Due to Parkinson’s-related motor imbalance, falls are a common consequence of the disease, and the risk of falling increases as patients get older and as the disease progresses.

Parkinson’s patients are twice as likely to fall than older adults living independently, and are also nine times more likely to have recurrent falls.

Observational studies suggest these patients underestimate the amount of work necessary for their muscles to produce a certain movement. They compensate for this lack of motor and perceptual ability by adopting distinct postural strategies to keep their balance during both static and dynamic movements.

Static measures of posture control can distinguish Parkinson’s patients from healthy older adults, but not Parkinson’s fallers from non-fallers.

“A better understanding of the relationship between falls and static and dynamic movements may provide further insight into falls-risk assessment in this clinical population,” the researchers said.

To study this, researchers at the University of Ottawa in Canada conducted a study that recruited 25 Parkinson’s patients and 17 healthy older adults used as controls.

They analyzed postural differences between Parkinson’s fallers and non-fallers, based on the self-reported occurrence of falls in the previous three months, and between healthy controls.

Motor disability was measured using the Unified Parkinson’s Disease Rating Scale III, cognitive impairment by the Montreal Cognitive Assessment, and freezing of gait by the Freezing of Gait questionnaire.

Participants were given static and dynamic motor tasks, consisting of one quiet standing condition and one walking condition (walking 15 meters while looking straight ahead).

Both tasks were presented twice and lasted for 30 seconds. Testing was performed while patients were optimally medicated with dopaminergic therapies.

The standing test was sensitive enough to distinguish between Parkinson’s patients and healthy controls, but not between fallers and non-fallers with Parkinson’s disease. However, static tasks were less sensitive in differentiating between fallers and non-fallers with Parkinson’s disease and healthy older adults than dynamic tasks.

Fallers had difficulty controlling their upper body (torso) when walking, compared with non-fallers and the control group. This was also true for individuals with Parkinson’s disease versus older healthy adults.

Importantly, falling was associated with static and dynamic postural control in Parkinson’s patients, with fallers and non-fallers adopting different postural strategies to regulate balance.

“Overall, this study provides useful information for falls-risk assessments as well as for developing fall prevention program specific to fallers and non-fallers with PD,” the researchers concluded.

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Source: Parkinson's News Today