The Parkinson Alliance

The Parkinson Alliance is using its 2019 distribution to fund:

PROJECT TITLE:  Pilot Study Expansion—Walking While Talking: Effects of dual-task on gait and cognition in individuals with Parkinson’s disease

Investigator/Author: Lisa M. Muratori, PT, EdD

Objective: Falls can be devastating for Parkinson’s patients, with 20-30% requiring hospitalization after a fall and a large percentage permanently losing their independence. For many PD patients, performing a simultaneous cognitive task such as talking while walking can negatively affect the speed and accuracy of their gait—potentially increasing fall risk while also reducing social participation and quality of life. Traditional physical therapy interventions often focus on the single task of walking, but there is a growing understanding that PT for individuals with PD must include dual-task training to maximize benefits. Our study aims to clarify the cognitive relationship between walking and talking, and develop new dual- and multi-task interventions that will directly benefit Parkinson’s patients.

Background: This study is an expansion of a pilot study led by Lisa M. Muratori, PT, EdD, which was funded by a seed grant from Stony Brook’s Thomas Hartman Center for Parkinson’s Research. Additional funding will enable us to expand the study to include data from additional participants, which will be key to establishing sufficient preliminary data to advance the study’s objectives and seek NIH funding for a multi-center trial.

Methods/Design: Our study will build on previously-funded pilot data to further determine whether an innovative game-based treadmill intervention will improve walking speed, decrease gait deviations, improve measures of functional mobility, improve verbal fluency, etc. for individuals with PD. Participants will complete standardized questionnaires measuring quality of life and fear of falling, plus 16 physical therapy testing/training sessions (30 minutes each, 3 times per week for 4 weeks). During the sessions, participants will walk on a treadmill with and without the support of a specialized safety harness. While walking, individuals will participate in a proprietary video-based immersive game that will interact with their treadmill and increase in difficulty each week. During each session, vital signs will be recorded and specific data will be collected using standardized tests including: Functional Reach test, 6-Minute Walk test, Timed Up and Go test, Stops Talking When Walking (STWW) test, and Controlled Oral Word Association (COWA) test. Movements will also be recorded using a state-of-the-art motion analysis system to determine how temporal and spatial characteristics of gait are altered. Using this information, we will develop new multi-task physical therapy interventions with applications beyond treadmill training—to improve over-ground walking, functional mobility, and social participation for Parkinson’s patients.  

Relevance to Diagnosis/Treatment of Parkinson’s Disease: In order to ensure full social participation and maintain optimal quality of life, while reducing fall risk, individuals with neurological disease must be able to safely move while engaging in decision making, social interactions, and other cognitive tasks. This study will lead to better physical therapy interventions to increase simultaneous motor and cognitive function for patients living with PD.

Expected Outcome: We expect our study to improve the scientific community’s understanding of the basis of cognitive and motor disturbances as they relate to PD. Testing will result in readily accessible and practical interventions for rehabilitation professionals working with PD patients, as well as preliminary data to pursue a larger clinical study.

November 2020 Project Update:

Since March 2020, Dr. Schwartz’s team has been working to translate A Matter of Balance to best meet the unique needs of people living with Parkinson’s Disease. To date, the team has developed a Parkinson’s-specific educational module, designed to supplement the current AMOB coach training. The educational module provides information specific to disease process, diagnosis, symptoms, fall risk factors, exercise and special considerations.

A coaches ‘toolkit’ is also in development and will include: a session-by-session “Special Considerations” fact sheet; Exercise and PD fact sheet; session-by-session curriculum modifications, including recommendations on how best to incorporate and support the care partner; and environmental modification fact sheet. Our team is currently working with Stony Brook University faculty to develop a student internship program, providing patient-specific, virtual learning opportunities for students while also innovating our program materials. The multi-disciplinary collaboration will allow us to recruit and train coaches from the healthcare field, as well as the broader community, increasing specialized training among our team and optimizing access to care for our patients and beyond.

October 2021 Project Update:

Stony Brook requested a no cost extension until 2-28-22 to ensure the adequate completion of this project. This was approved. Recruitment with Covid has been difficult. The PI has recruited 20 participants who have been willing to go to the lab multiple times for the study, however progress has been slow with all of the challenges that must be made based on the pandemic.

PROJECT TITLE:  Computational Modeling of 60 Hz Subthalamic Nucleus Deep Brain Stimulation for Gait Disorder in Parkinson’s disease

Investigator/Author: Ritesh Ramdhani, MD

Objective: The goal of this study is to further our understanding and application of 60Hz subthalamic deep brain stimulation (STN-DBS) in Parkinson’s patients with gait disorder. We and others have published studies showing low-frequency STN stimulation (60-80Hz) in chronic DBS patients may alleviate freezing and improve gait.

Methods/Design: We will assess the degree to which stimulation frequency parameters affect gait. The study will be conducted in two phases: The primary goal of Phase I is to establish a baseline movement profile of Parkinson’s subjects with DBS using motion sensors. The goal of Phase II is to investigate the impact of stimulation frequencies (60Hz and high) on gait characteristics. Each subject will be evaluated during an in-laboratory session for both phases under two conditions: 1) the practically defined OFF state following overnight withdrawal of their dopaminergic medications; and 2) levodopa ON State. We will then develop machine learning models to predict optimal subthalamic deep brain stimulation frequency.  

Relevance to Diagnosis/Treatment of Parkinson’s Disease: Gait disorder, which manifests as shuffling, reduction in speed, multistep turning, and/or freezing of gait (FOG), can arise later in the Parkinson’s disease (PD) course and cause significant disability. Ultimately, patients are at risk for falls and can become socially isolated due to their mobility limitations. These symptoms tend not to respond to high-frequency STN-DBS. However, lower frequency stimulation (60-80Hz) of the STN in treating gait disorder and/or freezing of gait has demonstrated benefit. This study potentially can expand knowledge of 60hz DBS while improving its utilization in combination with PD medications—enabling sustainable and possibly predictable therapeutic benefit.

Expected Outcome: This study will expand our understanding of DBS’s impact on gait problems in Parkinson’s patient. We expect that there will be a subset of patients who will benefit from 60Hz stimulation and that this cohort can be predicted from data-driven models.

November 2020 Project Update:

The investigator team effectively operationalized the simultaneous use of two sensor systems
(Mobility Lab and Kinesia) for assessing bradykinesia, tremor and gait and created the study’s
REDCAP database shortly afterwards. Enrollment began in Q2 with 5 subjects enrolled and 4
completing all assessments during this period. Study visits were suspended in March 2020 due to
COVID-19 pandemic.

Preliminary analysis on the small cohort demonstrated that 20% of measured gait parameters were statistically different between 60Hz and high frequency STN-DBS. Early computational models are demonstrating a 77% accuracy in identifying conditions with high frequency or 60hz stimulation within subjects. This proof of concept analysis was accepted as an abstract for presentation to the 2020 International Congress of Parkinson’s and Movement Disorders.

Study enrollment resumed in September 2020. There are 12 additional potential candidates who have been identified and meet inclusion criteria—three of whom have been scheduled for study visits in the fall of 2020. The investigator team have integrated COVID-19 safety precautions into the study protocol which includes: 1) Pre-appointment COVID screen; 2) COVID testing prior to the first study visit, 3) requirement for subjects to wear a mask and have temperature checked during study visits; 4) requirement for research staff to follow COVID-19 mask and hygiene policy. The study protocol was also modified to improve scientific rigor and reduce subject fatigue.

In an attempt to accelerate enrollment, our recruitment plan has been revised to include participant referrals from colleagues of established movement disorders centers in the Greater New York Region, online recruitment registries (e.g., CenterWatch), and the dissemination of a study-specific recruitment flyer.

October 2021 Project Update:

Study enrollment resumed in September 2020 with COVID safety precautions enacted within the protocol to reduce risk to study personnel and subjects. Ten subjects completed all assessments from Q4 2020 to Q4 2021 bringing the study enrollment total to 16.

The study team presented an abstract at the MDS Congress in 2020 demonstrating preliminary analysis of AIM 1 that 20% of measured gait parameters were statistically different between 60Hz and high frequency STN-DBS in a small cohort. Additionally, data driven modelling for AIM 2 are demonstrating 77% accuracy in identifying conditions with high frequency or 60Hz stimulation within subjects.

Furthermore, sub analysis on the cohort utilizing separate random forest (RF) models were built using sensor data under high frequency(HF) and 60hz DBS to predict gait and speech subscores of the MDS-Unified Parkinson’s Disease Rating Scale. The root mean squared error (RMSE) between RF predictions and speech and gait subscores are 0.56 (gait) and 0.65 (speech) for 60Hz and 0.63 (gait) and 0.78 (speech) for HF. Gait parameters (i.e., toe-off angle, cadence, double support cadence, upper and lower limb swing, trunk and lumbar range of motion), hand movement speed, and gender are important features in predicting gait and speech subscores under both 60Hz and HF. The results suggest that RF accurately predicts gait and speech MDS-UPDRS scores using sensor data under both 60Hz and high frequency STN-DBS—enabling the estimation of clinical ratings in both stimulation conditions . This analysis was accepted for a poster presentation at the 2021 MDS Congress.

The investigators are planning to complete enrollment by Q2 of 2022 and to publish the final results of the study shortly thereafter.