Donepezil for gait and falls in mild cognitive impairment: a randomized controlled trial

BACKGROUND AND PURPOSE: Cognitive enhancers are commonly prescribed to people with Alzheimer's disease and related dementias to improve cognition and function. However, their effectiveness for individuals in the pre-stages of dementia, particularly in functional motor outcomes, remains unknown. We aimed to determine the efficacy of donepezil, a cognitive enhancer that improves cholinergic neurotransmission, on gait performance in mild cognitive impairment (MCI). METHODS: This was a double-blind, placebo-controlled trial including 60 older adults with MCI, randomized to receive donepezil (10 mg/daily, maximal dose) or placebo. Primary outcome was gait speed (cm/s) under single and three dual-task conditions (counting backwards by 1 or 7 and naming animals) measured using an electronic walkway. Dual-task gait cost (DTC), a valid measure of motor-cognitive interaction, was calculated as the percentage change between single (S) and dual-task (D) gait speeds: [(S - D)/S] × 100. Secondary outcomes included attention, executive function, balance and falls. RESULTS: After 6 months, the donepezil group experienced an improvement in dual-task gait speed (range 4-11 cm/s), although this was not statistically significant. The donepezil group showed a significant reduction in DTC (improvement) by counting backwards by 1 and 7 compared with placebo (10.25% vs. 1.75%, P = 0.048; 21.38% vs. 14.64%, P = 0.037, intention-to-treat analysis). Per-protocol analyses showed that all three DTCs improved in the donepezil group, along with a non-significant reduction of rate of falls. CONCLUSIONS: Donepezil treatment improved dual-task gait speed and DTC in elderly patients with MCI. Our results support the concept of reducing falls in MCI by targeting the motor-cognitive interface.