Changes in Gait, Cognition May Be Early Signs of Idiopathic Parkinson’s, Research Suggests

gait and Parkinson's

Changes in gait and cognition precede a diagnosis of idiopathic (without known cause) Parkinson’s disease, and may occur earlier than typical non-motor symptoms, a study has found.

The study, “Prediagnostic markers of idiopathic Parkinson’s disease: Gait, visuospatial ability and executive function,” was published in Gait & Posture.

Motor symptoms in idiopathic Parkinson’s disease (IPD) are identified relatively late in the disease course, reducing the odds of neuroprotective benefit from available treatment options. Identifying individuals during the prodromal (early) period that precedes motor symptoms could be of great use for clinical studies seeking new therapies to prevent or delay disease progression.

A team of French researchers sought to determine the existence of any subtle gait disorders or other signs that precede the diagnosis of IPD, based on data from a long-standing study of human aging across the adult lifespan: the Baltimore Longitudinal Study of Aging (BLSA).

Conducted by the National Institute on Aging (NIA) Intramural Research Program, the BLSA continuously enrolls healthy volunteers age 20 and older who are followed throughout their life independently of the development of age-related diseases.

Ten pre-diagnosed IPD patients (eight men and two women) and 30 healthy control subjects were chosen for this study.

Subjects were assessed for the disease approximately 2.6 years before diagnosis. Clinical examination included gait speed, spatio-temporal gait parameters, balance, upper-limb motor skills, neuropsychological profile, and non-motor symptoms.

In comparison to the control group, IPD patients had shorter step length and reduced gait speed in a usual gait speed testing condition. Despite also having shorter step length when testing maximum gait speed, no differences between the IPD and control samples were found in walking speed.

Moreover, patients had worse mental rotation ability (the ability to rotate mental representations of two-dimensional and three-dimensional objects, which is related to the brain’s capacity for visual representation), and impaired ability to name different examples that could be inserted into a category (for instance, naming all types of flowers one can think of in one minute).

Compared to control subjects, IPD patients had no changes in upper-limb motor function, no depression, no sleep disturbances, no urinary symptoms, and no orthostatic hypotension (when blood pressure suddenly drops when standing up quickly).

Researchers concluded that the observed “changes might serve as markers to improve the early detection of IPD patients, who could then benefit from pharmacological neuroprotection trials and/or prevention trials of lifestyle-related interventions in order to delay, or even prevent, clinical manifestations.”

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Design, Development of BeatHealth System for Parkinson’s Gait Impairments Described in Study

BeatHealth system

Researchers have developed a system — a mobile app and two websites — based on musical stimuli to improve gait and reduce freezing episodes in Parkinson’s disease patients, according to a study describing the design process of the new approach.

The project, called BeatHealth, involved patients, caregivers, and health professionals from the start to produce the most useful, usable, and easy-to-use final system, with the most appropriate functionalities.

The study, “Design and development of a gait training system for Parkinson’s disease,” was published in PLOS ONE.

Parkinson’s main motor symptoms are typically associated with impaired gait. Rhythmic auditory stimulation (RAS), an approach that consists of matching a patient’s walking speed to a rhythmic sound, or piece of music, has shown beneficial effects in improving gait and reducing freezing episodes in people with Parkinson’s.

The BeatHealth system uses RAS in the form of musical stimuli and has been developed to deliver a training session for Parkinson’s patients. It consists of two sensors worn on the lower legs, a mobile application on a smartphone — which receives data from the sensors and is able to adapt the music rhythm to the user’s gait — and a cloud platform accessed through a website to store the information and allow healthcare professionals and patients to track gait progress.

BeatHealth’s design process was iterative and followed a user-centered methodology that incorporated the input of health professionals, patients, and caregivers.

This approach was intended to create an easy-to-use and easy-to-learn system over four phases: (1) research and exploration to adjust requirements, goals and context of use to the user; (2) concept and design to fulfill the requirements from phase one; (3) development and implementation, with input from users; and (4) evaluation of prototypes by final users to verify that requirements were met and to assess the system’s viability, usability, and functionality.

Personas, or fictional characters, interviews, standard validated questionnaires, and mock-ups were used along with the four phases. In the final phases, end-users also evaluated the system.

In phase one, 12 Parkinson’s patients and two relatives were interviewed about BeatHealth’s utility and its main functionalities. These patients were at various stages of disease severity and were also of different types of medication.

Ten patients said they would rather use this kind of system by themselves than under clinical supervision. Patients also indicated a preference for having access to step length, number of steps and time of training, and for using larger headphones due to hand function impairments.

Observation sessions were conducted in Montpellier, France, two with Parkinson’s patients and one with a healthy participant. The sessions were focused on better understanding the movement evaluation tools and techniques, as well as their impact on participants. The participants were mainly asked to walk around a marked circuit while listening to music with varying rhythmic characteristics.

In the third session, a patient had to complete tasks while using a memory app on a smartphone to evaluate issues related to managing a touch screen. Unlike when sitting or standing still, the patient was unable to complete any task when asked to walk.

“Witnessing this participant’s experience gave the observer a deeper understanding of user needs and the effects of [Parkinson’s] symptoms on the user’s interaction with their environment,” the researchers wrote.

Overall, the observation sessions led to breaking down the evaluation process into smaller parts, reducing multitasking, understanding the importance of motivation and goal-setting, simplifying data and instructions, designing the user interface, and establishing the distance to be walked during the task, as well as reducing the need for patients to enter data.

The scientists then decided to implement a web application, linked to one website for patients and another for health professionals, which, with patient authorization, enables the professional to create a training program for the patient and track his or her progress.

In phase two, the team generated paper prototypes initially evaluated by experts and stakeholders, but not by patients. A second mock-up was then created, which was evaluated by a team made up of a neurologist, a consultant, a physiotherapist, a patient, a human-computer interaction specialist, a computer science specialist, and a computer interaction designer.

Among the results of this second phase, the team found that the workflow required review to encourage the participants to send the data, the login screen needed simplification, the map screen required clarification, and volume buttons and text spacing needed improvement.

In phase three, a third version of the mock-up was evaluated, and the team focused on its viability. For the evaluation of the mobile app, four idiopathic (without known cause) Parkinson’s patients (one woman, three men, ages 64-74) with a walking disorder were recruited. They had to progress through a task flow using the prototype screens with additional tasks such as putting on sensors, connecting the charger, connecting headphones, or connecting to the WiFi network.

Interviews and discussions after the evaluation were aimed at addressing participants’ thoughts about the system, their evaluation experience, and any recommendations they had. The analyses showed that user experience in relation to connecting to WiFi and the time required to complete tasks needed improvement. In addition, the system needed further overall simplification and clarification.

A second evaluation of the mobile app was done by four patients (two women and two men, ages 46-84). They were asked to perform five tasks, which, in general, they were able to complete under appropriate guidance. They found the app user-friendly and simple, resulting in better usability and satisfaction over the previous version.

Website mock-ups were then evaluated by six patients, one relative of a Parkinson’s patient, and 11 healthcare professionals, who all valued the system’s simple and user-friendly structure. But healthcare professionals had difficulties finding particular functionalities, while patients mainly had problems in being able to read the text.

In phase four, the team incorporated changes based on the previous evaluations to create the final mobile application and websites. The most notable changes were to the home screen — such as direct access to music selection and user progress — and the screen flow associated with taking a walk.

Thirty-seven patients (20 women, ages 40-84) evaluated the final BeatHealth system over three months at home. Results showed that 78% of the participants were satisfied with the app, 72% found it easy to learn and understand, and 86% said it was clear enough. Issues with components such as sensors or phone buttons were the most frequent drawbacks. Satisfaction was higher than with the prototypes. However, only 32% of participants felt that the system helped them improve their gait.

“We can conclude that a complete methodology that involved stakeholders from the very beginning until the final evaluation of the design proved effective at producing a usable system in this particular case,” the researchers wrote.

Not measuring the system’s acceptance and adherence were among the study’s limitations and should be evaluated over longer trials, they noted.

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Study to Explore Art Therapy for Improving Visuospatial, Motor Function in Parkinson’s Patients

A new exploratory study intends to assess the benefit of art therapy in improving visuospatial function and gait in Parkinson’s disease patients.
The ExplorArtPD study (NCT03178786) is currently recruiting participants in New York City. More information on enrollment can be found here.
The study’s experimental protocol, “Visuospatial exploration and art therapy intervention in patients with Parkinson’s disease: an exploratory therapeutic protocol,” was published in the journal Complementary Therapies in Medicine.
Due to the variety of Parkinson’s motor and non-motor symptoms, including visuospatial dysfunction — loss of space orientation, motion perception, and target localization — effective treatments require multidisciplinary approaches involving physical therapy, occupational therapy, psychological support, family counseling, and palliative care.
When these approaches fail, complementary therapeutic strategies, such as art therapy, may hold potential to help patients restore functional independence and maintain their quality of life.
Although the source of visusospatial dysfunction in Parkinson’s is not fully understood, altered visual function has been consistently shown, with subsequent impaired ability to drive, read, and write, and increased anxiety and depression, as well as a greater risk of falls.
Given the lack of specific therapeutic strategies for visuospatial dysfunction associated with Parkinson’s disease, researchers at the Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders at NYU Langone Health developed an art therapy intervention protocol that includes psychotherapy and art creation to address visuospatial dysfunction and psychological needs of Parkinson’s patients.
The study is aimed at determining the characteristics of visuospatial exploration and its neural basis as assessed by clinical and behavioral tests, neuropsychological inventories, eye tracking, gait analysis, and brain magnetic resonance imaging (MRI). Researchers also intend to assess the therapeutic impact of art therapy on visuospatial dysfunction and gait in Parkinson’s patients.
“According to our preliminary data [art therapy] appears to be a safe, non-invasive, reproducible modality of intervention that could be administered to [Parkinson’s] patients with potential ease of recruitment,” the authors wrote.
The study has an anticipated enrollment of 40 participants, 20 of whom will have a clinical diagnosis of Parkinson’s disease and a Hoehn and Yahr scale stage of 2-3 — stage 2 meaning symptoms on both sides of the body, but no balance impairment, and stage 3 referring to balance impairment and mild to moderate disease. They must also have no history of clinically active eye abnormalities, and be eligible to undergo brain MRI scans. Researchers will also include 20 age-matched participants without Parkinson’s disease who will serve as controls.
Parkinson’s patients will undergo open-label art therapy and assessments both before the completion of art projects (baseline) and after completion (follow-up), while control participants will only undergo baseline assessments. In patients with motor fluctuations, the assessments will be made in the “on” state, when motor disability is milder and assessments can be performed with a lower risk of physical or psychological fatigue.
Art therapy will consist of 20 consecutive sessions lasting 90 minutes each, approximately twice per week for a maximum of 14 weeks. It will be administered by credentialed professionals with a master’s degree in art therapy. The approach will favor group dynamics, mutual support, and encouragement through shared projects.

Source: Parkinson's News Today

Sensor-Based Gait Analysis Can Enhance Individualized Evaluation of Parkinson’s Patients, Study Suggests

sensor-based gait assessment

Use of sensor-based methods to evaluate gait can improve individual assessments of Parkinson’s disease patients who are undergoing dopaminergic treatment, researchers suggest.

The study with that finding, “Sensor-based gait analysis of individualized improvement during apomorphine titration in Parkinson’s disease,” was published in the Journal of Neurology.

Gait impairment as a consequence of Parkinson’s disease progression can drastically reduce patients’ quality of life. However, available strategies to evaluate gait alterations for individual patient care are still limited.

More recently, the development of mobile sensor-based gait analysis methods has enabled the objective assessment of gait deficits in Parkinson’s patients. Still, the applicability and effectiveness as an individualized evaluation approach has not been established.

A team led by researchers at FAU Erlangen-Nürnberg in Germany compared gait outcomes measured with standard and sensor-based methods in Parkinson’s patients undergoing dopamine replacement therapy.

The study enrolled 13 patients who had mean disease duration of about 15 years and were receiving a mean levodopa equivalent daily dose of 1,077 mg.

All participants started treatment with Apokyn (apomorphine) according to standard protocol, by injecting a defined dose subcutaneously (under the skin) every 15 minutes until achieving the best motor response. Apokyn is an injectable agent usually used to restore body movement control between doses of levodopa, during “off” periods — periods when medication wears off and symptoms reappear.

To track gait movement, researchers used sensors (3D-acceerometers and 3D-gyroscopes) attached to the shoes that could detect small changes in movement orientation and speed. These sensors measure parameters such as rotation and dynamic acceleration resulting from motion, shock or vibration, and can measure tremor in these patients.

After treatment with Apokyn, patients showed a significant improvement in gait movement, as shown by increase in certain gait parameters, including stride speed and length, maximum toe clearance, gait velocity, swing time, heel strike angle, and toe-off angle.

To better evaluate the potential of sensor-based gait analysis to perform individualized evaluations, researchers compared the data obtain between Apokyn administrations within in each patient.

This strategy allowed them to confirm that sensor-based results could effectively measure small gait differences resulting from Apokyn dosages. It could discriminate significant improvements in stride speed, length, and time, and maximum toe clearance between two sequential administrations, as well as detect when no additional improvements were achieved with higher doses.

To validate these findings, researchers compared the sensor-based data with motor scores collected with the standard measure Unified Parkinson Disease Rating Scale (UPDRS) (a 50-question assessment of both motor and non-motor symptoms associated with Parkinson’s).

Improvement in gait parameters (obtained using sensor-based gait analysis) between Apokyn injections reflected improvement in patients’ overall motor performance as measured by the UPDRS, in particular in items related to postural stability and gait.

“[S]ensor-based gait analysis provides objective target outcome measure of gait performance, reflecting apomorphine-induced improvement of motor performance in [Parkinson’s disease],” researchers wrote.

“We show that using instrumented gait analysis to measure individual changes in gait parameters … may be a powerful assessment strategy for routine clinical care in individual [Parkinson’s disease] patients,” they concluded.

However, the authors caution that additional studies in larger groups of patients are still warranted to further validate the applicability and implementation of sensor-based gait analysis as an objective and individualized diagnostic tool for real-life healthcare.

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Beat It! Learning to Walk to Music Reduces Falls for Parkinson’s Patients

walking and music

A training program in which patients walk while listening to regular beats can improve the velocity and cadence of Parkinson’s disease patients, while reducing their risk of falling, a study shows.

The study, “Rhythmic auditory stimulation for reduction of falls in Parkinson’s disease: a randomized controlled study,” was published in the journal Clinical Rehabilitation.

Parkinson’s disease patients experience difficulties in movement that affect their ability to produce a steady gait, resulting in a high incidence of falls. More than half of all Parkinson’s patients fall recurrently.

While there are several training techniques to aid in maintaining a steady gait and avoiding falls, studies suggest that gait motor control is dependent on a patient’s internal timing and that rhythm-based training could reduce risk of falling.

The rhythmic auditory stimulation (RAS) technique is among the approaches used to synchronize gait movements with time cues. But there have been no studies assessing the benefits of RAS in Parkinson’s patients.

So, researchers in Canada set out to determine if a home-based RAS program could aid in decreasing falls in patients with that history.

The study was a randomized, controlled trial (NCT03316365) that involved 60 Parkinson’s patients, 47 of whom completed the study.

The RAS training protocol involved 30 minutes of daily walking using “click-embedded music,” which was designed to enhance rhythm perception. Essentially, patients listened to folk or classical music with embedded metronome beats while performing their walking exercises.

Participants were divided into two groups, experimental and control. Both groups received RAS training up to week 8, after which the control group stopped training and the experimental group continued. Then  training was resumed for the control group between weeks 16 and 24. Patients in the experimental group received RAS training for the entire 24 weeks.

Participants were assessed at the beginning of the study and at eight, 16, and 24 weeks following that. Assessment criteria included stride length, speed, balance, and falls.

As expected, no significant differences were seen between the two groups at week eight. However, at week 16, the experimental group showed significant improvement in velocity, cadence, stride length, decreased number of falls, and fear of falling compared to the control group.

At week 24 — after the control group had resumed RAS training — the signifiant differences in velocity, cadence, stride length, and fear of falling remained, but there were no longer significant differences in the number of falls.

Taken together, the findings indicate that “RAS gait training significantly reduced the number of falls and modified key [parameters] in gait control in patients with Parkinson’s disease,” researchers wrote.

“This clinical investigation demonstrates that RAS gait training is a potential intervention to reduce the risk of falling, since it directly addresses temporal instability, which is one of the most detrimental variables associated with falls,” they concluded.

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Socks with Sensors Being Tested to Detect Early Signs of Walking Disorders, Parkinson’s


Special socks using a wearable fitness-tracking technology are being investigated in a pilot study to see if they can detect early signs of movement or walking disorders, like Parkinson’s disease, or  in people.

Inspired by technology like Fitbit  — wearable equipment that track fitness performance like daily steps and heart rate — researchers at Old Dominion University in Virginia, working in collaboration with neurologists at Sentara Healthcare, are using washable socks wired with special sensors capable of tracking movement, detecting step numbers and gait patterns that might reveal clinical evidence of problems.

Developed Sensoria, these noncommercial fitness socks include a removable device capable of recording five to seven days’ worth of information, and sensors that can measure gait, acceleration and balance, according to a news story in  The Virginian-Pilot. Data is held in a small device attached to the socks, which can then be downloaded to a computer or sent to a smartphone or tablet.

A two-part pilot study is now underway in university students. If the data seem accurate, a second-part is planned involving 60 older adults — a mix of healthy people serving as controls and Parkinson’s patients, with both groups wearing the socks for seven days, the news article states.

“The ‘silver tsunami’ of older adults over the age of 65 is expected to double over the next 20 to 30 years,” Steven Morrison, an ODU professor and director of research for the School of Physical Therapy and Athletic Training, said in a university press release. “We are going to have more older adults at risk for falls, so anything we can do to decrease that risk will be better for the population as a whole.”

If all goes well, the researchers plan to reach out to Parkinson’s groups like the Michael J. Fox Foundation and  the National Institutes of Health (NIH) to support further studies into this fitness technology and its ability to detect problems before symptoms are evident, or a need for changes in treatment given someone with a disease diagnosis.

A YouTube video on this pilot study is available here.

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Brain Training, Medication Could Reduce Parkinson’s Patients’ Falls, Study Reports

Ways to reduce falls

Brain training can improve the mobility and reduce the risk of falls among older people with dementia and cognitive impairment, a study reports.

Another finding was that medication that improves cognition can decrease the risk of Parkinson’s patients falling.

The research, “Falls in Cognitively Impaired Older Adults: Implications For Risk Assessment And Prevention,” was published in the Journal of the American Geriatrics Society.

Recent studies have shown that in addition to muscle, joint and sensory impairment, cognitive dysfunction — difficulty thinking and making decisions — plays a key role in falls.

In older people, dementia and falls frequently co-exist. In fact, walking difficulties and falls are a bigger problem in those with dementia than in those with normal cognition. And the problem increases with the severity of cognitive impairment.

In the U.S., about a third of older adults fall every year. They are a major cause of medical problems.

This is especially true for people with dementia or other cognitive problems. They are five times more likely to be admitted to long-term care facilities. They are also at higher risk of fractures, head injuries, and death than older people without dementia.

To identify strategies to prevent falls and better assess the link between walking and cognition, Canadian scientists reviewed several studies that dealt with the role cognitive function plays in falls. They also looked at ways of improving cognitive function as a potential strategy for preventing falls.

A key finding was that poor performance on tests of a person’s ability to pay attention and on their decision-making correlated with slow and unstable walking, and falls. Another finding was that medications that improve cognition, such as the central nervous system stimulant methylphenidate (Ritalin), can decrease Parkinson’s patients’ falls.

The team also discovered that lower levels of the neurotransmitter acetylcholine in the brain increase the chance that Parkinson’s patients will have attention problems, walk very slowly, and fall. Treatments that can increase acetylcholine levels could improve patients’ movement, they said.

“Mounting evidence supports [the idea] that pharmacological interventions may reduce falls in [Parkinson’s] populations,” the researchers wrote. They called for testing such treatments in patients prone to falling to see whether they can reduce the problem.

In addition, the team said certain types of brain training — cognitive training, cognitive and motor dual‐task training, and virtual reality training — might be able to improve the mobility of sedentary older people and those with cognitive impairment and dementia.

The team also found that people with mild cognitive impairment were at greater risk of developing dementia and falling. This means doctors should offer fall-reduction strategies to this group in particular, the researchers said.

“[Understanding] the mechanism and contribution of cognitive deficits in fall risk may open new treatment approaches,” they concluded.

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Michael J. Fox Foundation Announces New $7M Initiative to Support Parkinson’s Research, Therapy Development

Michael J. Fox Foundation

The Michael J. Fox Foundation (MJFF) announced a new $7 million funding program to support Parkinson’s disease research and accelerate development of new therapeutic targets and biomarkers.

Through the program, researchers can request project funding in four major research areas. The organization is now accepting pre-proposals through May 2018, with funding anticipated by November 2018.

“We are working diligently toward breakthroughs for people with Parkinson’s and are committed to helping make therapy options available to treat the disease,” Todd Sherer, PhD, chief executive officer of MJFF, said in a press release. “The targeted funding programs announced today will fuel cutting-edge research in areas of significant scientific potential, providing multiple shots on goal.”

One of the four research areas will dedicate $2 million to study nonpharmacological interventions for gait and balance disturbances, two of the most troubling and under-addressed aspects of the disease.

Parkinson’s patients suffer from frequent falls, injury, loss of independence, and decreased quality of life due to problems with gait and balance. Current therapies are insufficient to improve challenges in this area.

The program will fund research projects seeking to gain a deeper insight of the brain circuitry and clinical experience of gait and balance problems. It will also fund studies to investigate the therapeutic benefit of assistive devices, novel technologies, or rehabilitative therapy programs. Excluded from this funding are exercise programs or cognitive strategies.

An additional $1.5 million will be geared toward studying the protein alpha-synuclein, the major component of Lewy bodies, protein clumps found in virtually every Parkinson’s patient’s brain and body cells. To test if Lewy bodies may play a causal role in the disease’s onset and progression, the program will fund researchers seeking to deepen understanding of alpha-synuclein and refine therapy development.

The foundation has also allocated $1.5 million to fund projects investigating GBA protein dysfunction and mutations in the GBA gene in Parkinson’s and speed learning toward practical therapies.

GBA mutations are among the most common in Parkinson’s disease, found in 5 to 10 percent of patients. However, alterations of the normal GBA protein have been found in patients who are not carriers of the GBA mutation, making it a particularly promising target in the development of new therapeutic targets.

A fourth area of research will have a dedicated budget of $2 million. The program will fund researchers seeking to develop and test biomarker assays in three relevant areas: protein handing/autophagy, exosomes, and lipidomics.

Objective measures of Parkinson’s risk, onset, and progression are critical to transform patient care and therapy development. Biomarkers are not only useful to enable an early and accurate diagnosis, but they are also particularly important for more efficient, cost-effective clinical trials. To date, no objective biomarker for Parkinson’s has been developed.

The deadline for pre-proposal submissions is 5:00 p.m. EST May 31, 2018.

MJFF will host an informational webinar at 12:00 p.m. EST May 10 to review the aims of the program and to detail funding process and applicant questions.

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