title: Donepezil improves gait performance in older adults with mild Alzheimer's disease: a phase II clinical trial.
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).
  
  
  CONCLUSIONS
  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.
authors: "Gait and Brain Lab", Parkwood Hospital and Lawson Health Research Institute, London, ON, Canada Department of Medicine, Division of Geriatric Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada Department of Epidemiology & Biostatistics, Schulich Interfaculty Program in Public Health, University of Western Ontario, London, ON, Canada.
authors: Manuel
authors: M
authors: Montero-Odasso
authors: "Gait and Brain Lab", Parkwood Hospital and Lawson Health Research Institute, London, ON, Canada Department of Medicine, Division of Geriatric Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
authors: Susan W
authors: SW
authors: Muir-Hunter
authors: "Gait and Brain Lab", Parkwood Hospital and Lawson Health Research Institute, London, ON, Canada.
authors: Afua
authors: A
authors: Oteng-Amoako
authors: "Gait and Brain Lab", Parkwood Hospital and Lawson Health Research Institute, London, ON, Canada.
authors: Karen
authors: K
authors: Gopaul
authors: "Gait and Brain Lab", Parkwood Hospital and Lawson Health Research Institute, London, ON, Canada.
authors: Anam
authors: A
authors: Islam
authors: Department of Medicine, Division of Geriatric Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
authors: Michael
authors: M
authors: Borrie
authors: Department of Medicine, Division of Geriatric Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
authors: Jennie
authors: J
authors: Wells
authors: Department of Epidemiology & Biostatistics, Schulich Interfaculty Program in Public Health, University of Western Ontario, London, ON, Canada.
authors: Mark
authors: M
authors: Speechley
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D018726:Anti-Dyskinesia Agents / Q000627:therapeutic use*; D001288:Attention / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D000077265:Donepezil; D056344:Executive Function / Q000187:drug effects; D005260:Female; D005684:Gait / Q000187:drug effects*; D020233:Gait Disorders, Neurologic / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018726:Anti-Dyskinesia Agents; D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil
keywords: Aged; Alzheimer's disease; cholinesterase inhibitors; clinical trials; donepezil; executive function; falls; gait