Objective: To analyze risk factors for falls in individuals with Lewy Body Dementia (LBD) enrolled in PRESENCE.

Background: PRESENCE was a phase 2 clinical trial assessing the efficacy of mevidalen, a D1 receptor positive allosteric modulator, for the symptomatic treatment of LBD. Mevidalen demonstrated improvements in motor and non-motor features of LBD, global functioning and actigraphy measures of activity and daytime sleep. However, adverse events (AE) of fall were numerically increased in mevidalen treated participants.

Method: Participants enrolled in PRESENCE wore a wrist-actigraphy device for three separate 2-week periods: pre-treatment, during treatment, post-treatment. Baseline variables including demographics and disease characteristics were pre-specified and were tested to evaluate differences between fallers and non-fallers. Analysis of treatment-emergent changes was conducted for actigraphy endpoints and relevant scales that indicated reduced or increased risk for falls. Activity and sleep measurements derived from actigraphy were aggregated per period and analyzed to assess for their association with participants who reported an adverse event of fall (fallers). Independent samples t-test were conducted to compare the means between fallers and non-fallers.  Chi-square test was applied to compare proportion of fallers to non-fallers (R 4.0.3).

Results: Higher body mass index and more severe disease as measured by baseline MDS-UPDRS Part II were associated with being a faller (P<0.05). Mevidalen treatment was not statistically significant (P=0.05) and therefore weakly associated with falls. Analysis of treatment-emergent changes conducted for actigraphy endpoints showed non-significant improvements in relevant scales measured by ADAS-cog 13 and MDS-UPDRS Part II. In addition, increased activity and reduced daytime sleep as derived from actigraphy were associated with fallers.

Conclusion: The association of falls with baseline disease severity and BMI, and overall improvements of activity and daytime sleep suggest that falls in PRESENCE may be related to increased activity in mevidalen-treated participants at the greatest risk for falling. Future trials of mevidalen using fall diaries and digital assessments are necessary to confirm this hypothesis.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/utilizing-digital-biomarkers-to-explore-risk-factors-for-falls-in-patients-with-lewy-body-dementia/