Affiliations: [a] “Gait and Brain Lab”, Parkwood Hospital and Lawson Health Research Institute, London, ON, Canada | [b] Department of Medicine, Division of Geriatric Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada | [c] Department of Epidemiology & Biostatistics, Schulich Interfaculty Program in Public Health, University of Western Ontario, London, ON, Canada
Correspondence:
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Correspondence to: Manuel Montero-Odasso MD, PhD, AGSF, Gait and Brain Lab, Parkwood Hospital, Rm. A-280, Western University and Lawson Health Research Institute, 801 Commissioners Rd East, London, ON, N6C 5J1, Canada. Tel.: +1 1519 685 4292; ext. 42369, Fax: +1 519 685 4093; E-mail: mmontero@uwo.ca.
Abstract: Background:Gait deficits are prevalent in people with dementia and increase their fall risk and future disability. Few treatments exist for gait impairment in Alzheimer's disease (AD) but preliminary studies have shown that cognitive enhancers may improve gait in this population. Objective:To determine the efficacy of donepezil, a cognitive enhancer that improves cholinergic activity, on gait in older adults newly diagnosed with AD. Methods:Phase II clinical trial in 43 seniors with mild AD who received donepezil. Participants had not previously received treatment with cognitive enhancers. Primary outcome variables were gait velocity (GV) and stride time variability (STV) under single and dual-task conditions measured using an electronic walkway. Secondary outcomes included attention and executive function. Results:After four months of treatment, participants with mild AD improved their GV from 108.4 ± 18.6 to 113.3 ± 19.5 cm/s, p = 0.010; dual-task GV from 80.6 ± 23.0 to 85.3 ± 22.3 cm/s, p = 0.028. Changes in STV were in the expected direction although not statistically significant. Participants also showed improvements in Trail Making Tests A (p = 0.030), B (p = 0.001), and B-A (p = 0.042). Conclusion:Donepezil improved gait in participants with mild AD. The enhancement of dual-task gait suggests the positive changes achieved in executive function as a possible causal mechanism. This study yielded a clinically significant estimate of effect size; as well, the findings are relevant to the feasibility and ethics considerations for the design of a Phase III clinical trial.
