Digital Biomarkers of Disease Severity in Progressive Supranuclear Palsy
Ashkan Vaziri1, Ram Kinker Mishra1, Ilkay Yildiz Potter1, AJ Hall2, Jesse Wang3, Catherine Isroff3, Claudia Waddell2, Tejas Pawar1, Amanda O'Brien1, Rylee Cole1, Alexander Pantelyat2, Anne Marie Wills3
1Biosensics LLC, 2Johns Hopkins University School of Medicine, 3Massachusetts General Hospital, Harvard Medical School
Objective:
To assess the feasibility and utility of digital health technologies for monitoring disease severity in progressive supranuclear palsy (PSP) over time.
Background:

Clinical scales such as the PSP Rating Scale (PSPRS) are widely used in assessing disease severity in PSP but are limited by infrequent administration and observer bias. Objective, ecologically valid digital biomarkers may provide greater sensitivity to disease evolution, reduce patient travel burden, and enhance therapeutic development.

Design/Methods:

We enrolled 43 individuals with PSP (mean age 71.3 ± 7.9 years; 21 female) across two CurePSP Centers of Care (Massachusetts General Hospital and Johns Hopkins University). Participants completed up to 12 months of multimodal monitoring, with assessments every 3 months (baseline, 3, 6, 9, and 12 months). Monitoring included at-home wearable activity tracking with PAMSys™ pendant sensors and tablet-based digital speech, cognitive and fine motor assessments via the BioDigit Home™ platform. Clinical assessments (mPSPRS) were conducted in person or remotely. Digital measures were analyzed and compared with relevant clinical scores.

Results:
Wearable-derived activity measures correlated significantly with disease severity. For example, total steps (R = −0.28, p = 0.0114), sit-to-stand transitions (R = −0.38, p = 0.0005), and total walking time (R = −0.293, p = 0.008) declined with worsening mPSPRS, while step-duration variability increased (R = 0.433, p = 0.0001). Digital speech, cognitive and fine motor control outcomes also showed significant correlations with disease severity.
Conclusions:

Digital biomarkers exhibited associations with PSP severity across motor, speech, and cognitive domains. These findings demonstrate the feasibility of remote monitoring and emphasize the importance of developing digital endpoints as sensitive and low-burden outcome measures for clinical studies in PSP.

10.1212/WNL.0000000000216985
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