Digital Health Technologies for Progressive Supranuclear Palsy and Dementia With Lewy Bodies

PSP is a severe and rapidly progressive frontotemporal lobar degeneration (FTLD) syndrome that lacks effective treatment and leads to a rapid onset of dementia, disability, and eventually death. Dementia with Lewy bodies (DLB) is the second most common type of neurodegenerative dementia after Alzheimer's disease that severely impacts daily function and shortens lifespan. Mild cognitive impairment with Lewy bodies (MCI-LB) is an earlier stage where cognitive impairment is noticeable, but does not significantly interfere with living to the degree as seen in DLB. Both PSP and DLB cause significant motor impairment, resulting in progressive loss of independence in activities of daily living, such as eating, dressing, and writing. Despite approximately 200 ongoing clinical trials in PSP and DLB, there are no FDA-approved treatments for FTLD syndromes (including PSP) or DLB. One of the key challenges in the development of new effective therapies for DLB syndromes is the lack of validated instruments and biomarkers to measure disease severity, disease progression, and the effect of therapeutic interventions. Clinical measures of PSP and DLB, largely based on quantitative variations on the neurological exam, have suboptimal sensitivity to change and relevance to clinical meaning in patients' lives. Since 2019, BioSensics, MGH and JHU have partnered to develop a remote monitoring solution for FTLD syndromes using wearable sensors and a series of digital assessments. The solution uses PAMSys, a FDA-listed Class II pendant sensor for monitoring physical activity, posture, and walking parameters during activities of daily living, where the investigators have demonstrated the feasibility of using PAMSys for tracking ambulatory change in PSP. In this project, the investigators will use PAMSys pendant, PAMSys ULM wrist sensors, and PAMSys Gait ankle sensors to enable comprehensive monitoring of upper and lower limb function in PSP and DLB. The will demonstrate the accuracy (analytical validation) of PAMSys, PAMSys ULM and PAMSys Gait sensors in PSP and DLB. Digital speech, fine motor control, and cognitive assessment data will also be collected from the participants using a study tablet. In addition, a proof-of-concept study will be conducted to demonstrate the feasibility and reliability of monitoring motor function in PSP and DLB using the wearable sensors. Clinically, the proposed solution can be used to develop more sensitive approaches to monitor an individual's response to new therapies. Such solutions can enable the detection of subtle changes in movement, ambulation, and motor function while providing specific individualized insights into the clinical phase of disease. Additionally, by testing whether disease outcomes can be measured remotely in patients' homes, this project will be a crucial step forward for both research and clinical care that could meaningfully reduce both financial and time costs for patients, clinicians, researchers, and pharmaceutical companies.

• Schwab and England Activities of Daily Living (SE-ADL) [Time frame: Baseline.]
• Zaret Burden Interview (ZBI) [Time frame: Baseline.]
• Symbol Digit Modalities Test (SDMT) [Time frame: Baseline.]
• Montreal Cognitive Assessment (MoCA) [Time frame: Baseline.]
• Patient Global Impression Scale (PGIS) [Time frame: Baseline.]