Objective: To evaluate if wrist actigraphy data can derive clinically meaningful information reflecting circadian rhythm and motor functions from patients with Lewy body dementia (LBD) in PRESENCE.

Background: PRESENCE (NCT:03305809) was a phase 2 clinical trial assessing mevidalen (LY3154207), a D1 receptor positive allosteric modulator, to treat symptoms of LBD [1]. Participants were randomized to daily doses (10, 30 or 75 mg) of mevidalen or placebo for 12 weeks. Passively collected wrist-worn actigraphy data can potentially assess circadian rhythm and motor functions objectively in patients with LBD.

Method: Participants enrolled in PRESENCE continuously wore an actigraphy device on the non-dominant hands for three separate 2-week periods: pre, during (week 7 and week 8 after treatment starts), and post-treatment. From actigraphy data, the circadian rhythm and motor function measures are derived and assessed for correlation with Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) during the pretreatment period. The treatment effect was determined as change from baseline, using Mixed Model Repeated Measures analysis. Pearson’s correlation coefficients compared actigraphy data with clinical measures and unadjusted p-values are reported.

Results: At baseline, actigraphy-derived circadian rhythm measure, M10L5 [2], correlated with MDS-UPDRS part II (r=-0.44, p<0.001); actigraphy-derived bradykinesia measure [3] correlated with MDS-UPDRS total bradykinesia score (r=-0.39, p<0.001); actigraphy-derived tremor measure [4] correlated with MDS-UPDRS total tremor score (r=0.51, p<0.001). Dose-dependent improvements in actigraphy-measured circadian rhythm (p<0.01, p<0.01, p<0.001 at 10 mg, 30 mg, and 75 mg doses, respectively) and bradykinesia measure (statistically significant at 10 mg dose, p<0.01, and 75 mg dose, p<0.001) relative to placebo were observed, returning to baseline post-treatment. Actigraphy-derived tremor measure showed statistically significant treatment effect at 30 mg dose (p<0.05) and 75 mg dose (p<0.05).

Conclusion: The results demonstrate promising application of passively collected actigraphy data using a low burden device to obtain clinically meaningful insight in circadian rhythm, bradykinesia, and tremor from patients with LBD.

References: [1] J. Wang, C. Battioui, A. Mccarthy, X. Dang, H. Zhang, A. Man, J. Kyle, L. Munsie, M. Pugh, K. Biglan. Evaluating the use of digital biomarkers to test treatment effects on cognition and motor in patients with Lewy Body Dementia [abstract]. Mov Disord. 2021; 36 (suppl 1). 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/. Accessed February 28, 2022.
[2] Witting W, Kwa IH, Eikelenboom P, Mirmiran M, Swaab DF. Alterations in the circadian rest-activity rhythm in aging and Alzheimer’s disease. Biol Psychiatry. 1990;27(6):563-572. doi:10.1016/0006-3223(90)90523-5
[3] Griffiths RI, Kotschet K, Arfon S, Xu ZM, Johnson W, Drago J, Evans A, Kempster P, Raghav S, Horne MK. Automated assessment of bradykinesia and dyskinesia in Parkinson’s disease. Journal of Parkinson’s disease. 2012 Jan 1;2(1):47-55.
[4] Luft F, Sharifi S, Mugge W, Schouten AC, Bour LJ, van Rootselaar AF, Veltink PH, Heida T. A power spectral density-based method to detect tremor and tremor intermittency in movement disorders. Sensors. 2019 Jan;19(19):4301.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/evaluation-of-actigraphy-based-circadian-rhythm-and-motor-function-measures-for-monitoring-treatment-of-lewy-body-dementia-in-presence-study/