Evaluating the Use of Digital Biomarkers to Test Treatment Effects on Cognition and Movement in Patients with Lewy Body Dementia.

Background: PRESENCE was a Phase 2 trial assessing mevidalen for symptomatic treatment of Lewy body dementia (LBD). Participants received daily doses (10, 30, or 75 mg) of mevidalen (LY3154207) or placebo for 12 weeks.

Objective: To evaluate if frequent cognitive and motor tests using an iPad app and wrist-worn actigraphy to track activity and sleep could detect mevidalen treatment effects in LBD.

Methods: Of 340 participants enrolled in PRESENCE, 238 wore actigraphy for three 2-week periods: pre-, during, and post-intervention. A subset of participants (n = 160) enrolled in a sub-study using an iPad trial app with 3 tests: digital symbol substitution (DSST), spatial working memory (SWM), and finger-tapping. Compliance was defined as daily test completion or watch-wearing ≥23 h/day. Change from baseline to week 12 (app) or week 8 (actigraphy) was used to assess treatment effects using Mixed Model Repeated Measures analysis. Pearson correlations between sensor-derived features and clinical endpoints were assessed.

Results: Actigraphy and trial app compliance was > 90% and > 60%, respectively. At baseline, daytime sleep positively correlated with Epworth Sleepiness Scale score (p < 0.01). Physical activity correlated with improvement on Movement Disorder Society -Unified Parkinson Disease Rating Scale (MDS-UPDRS) part II (p < 0.001). Better scores of DSST and SWM correlated with lower Alzheimer Disease Assessment Scale -Cognitive 13-Item Scale (ADAS-Cog13) (p < 0.001). Mevidalen treatment (30 mg) improved SWM (p < 0.01), while dose-dependent decreases in daytime sleep (10 mg: p < 0.01, 30 mg: p < 0.05, 75 mg: p < 0.001), and an increase in walking minutes (75 mg dose: p < 0.001) were observed, returning to baseline post-intervention.

Conclusion: Devices used in the LBD population achieved adequate compliance and digital metrics detected statistically significant treatment effects.