Objective: To evaluate if frequent cognitive and motor tests using an iPad app and a wrist-worn actigraphy watch to track activity and sleep can detect mevidalen (LY3154207) effects in patients with Lewy Body Dementia (LBD).

Background: PRESENCE was a phase 2 clinical trial assessing mevidalen for symptomatic treatment of LBD. Participants received daily doses (10, 30 or 75mg) of mevidalen or placebo. Devices were used to evaluate cognitive, motor, activity and sleep effects of mevidalen.

Method: Participants (n=234) enrolled in PRESENCE wore the watch 24/7 for three separate 2-week (w) periods: pre-, during, and post-treatment. A subset of participants (n=160) enrolled in a sub-study using an iPad trial app with digital symbol substitution (DSST), spatial working memory (SWM) [1] and finger-tapping tests [2]. During pre- and post-treatment, participants performed tests twice daily, and during treatment, once daily. Compliance was defined as daily test completion or watch-wearing ≥23 hours/day. Change from baseline to w12 (app) or w8 (actigraphy) on pre-specified endpoints of DSST, SWM, finger tapping, and actigraphy-measured activity and sleep were used to assess treatment effects using Mixed Model Repeated Measures analysis. Pearson correlations between sensor-derived features and clinical endpoints were assessed.

Results: Actigraphy compliance was >90% and trial app compliance was >60%. At baseline, actigraphy-measured daytime sleep positively correlated with Epworth Sleepiness Scale score (r=0.19, p<0.01). Physical activity correlated with improvement on MDS-UPDRS part II (r=-0.3, p<0.001). Better scores of DSST and SWM correlated with lower ADAS-Cog13 (DSST: r=-0.53, p<0.001; SWM: r=-0.61, p<0.001) and higher MOCA (DSST: r=0.48, p<0.001; SWM: r=0.52, p<0.001). Dose-dependent increases in actigraphy-measured daytime sleep (p<0.05, 0.01, 0.001 for 3 doses), and walking minutes (statistically significant at the 75 mg dose (p<0.001)) relative to placebo were observed, returning to baseline post-treatment. The 30 mg mevidalen treatment improved SWM (p<0.01) from baseline to w12 relative to placebo. No statistically significant treatment effect was observed in DSST or finger tapping.

Conclusion: The results demonstrated that devices used in the LBD population achieved adequate compliance and derived digital metrics detected statistically significant treatment effects.

References: [1] Brain Baseline https://www.brainbaseline.com/ [2] Bot, B. M. et al. The mPower Study, Parkinson disease mobile data collected using ResearchKit. Sci. Data 3:160011 (2016)

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MDS Abstracts - https://www.mdsabstracts.org/abstract/evaluating-the-use-of-digital-biomarkers-to-test-treatment-effects-on-cognition-and-motor-in-patients-with-lewy-body-dementia/