A meta‐analysis of randomised controlled trials of physical activity in people with Alzheimer's disease and mild cognitive impairment with a comparison to donepezil

Abstract

Objectives Physical exercise may benefit people with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, randomised controlled trials (RCTs) of exercise have shown conflicting findings and it is unclear if positive outcomes are comparable to a commonly used cholinesterase inhibitor, donepezil. Methods Embase, Medline, PsycINFO, PsycARTICLES, SCOPUS were searched for RCTs of physical activity compared to a control condition, and donepezil compared to placebo in people with AD and MCI. Effect sizes were calculated from pre‐ and post‐MMSE and ADAS‐Cog scores and pooled using a random effects meta‐analysis. Results Ninteen RCTs were included in the exercise meta‐analysis (AD, N = 524; MCI, N = 1269). Physical exercise improved MMSE scores in AD (Hedges' g = 0.46) and MCI groups (g = 0.63). For the MCI group, exercise appeared to have a stronger effect for those with lower MMSE scores at baseline (p = 0.022). 18 RCTs were included in the donepezil meta‐analysis (AD, N = 2984, MCI, N = 1559). In people with AD, donepezil improved cognition (MMSE g = 0.23; ADAS‐Cog, g = −0.17) but there was no evidence of improved cognition in MCI. Conclusions Physical exercise improved cognition in both AD and MCI groups. Where comparisons were possible, the effect size for physical exercise was generally comparable to donepezil. These results strengthen the evidence base for exercise as an effective intervention in AD and MCI, and future clinical trials should examine exercise type, intensity and frequency, in addition to cholinesterase inhibitors to determine the most effective interventions for AD and MCI.

Physical Activity Improves Cognition and Activities of Daily Living in Adults with Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Although many meta-analyses have indicated the effects of exercise on adults with AD [17,27,53], there are differences in selection criteria between our study and previous studies. Due to the different mechanisms of dementia, abnormal protein deposits may coexist with neuro-vasculature at different stages of dementia and influence brain function [54].…”

“…Although many systematic review studies have examined the effects of exercise on cognition and physical performance in adults with AD, they have commonly shown inconclusive results due to inconsistent inclusion criteria, considerable heterogeneity (I 2 ≈ 80%) across studies, a small number of included studies, and different types of dementia populations (e.g., Lewy body dementia and vascular dementia) [16,17,27]. They have considered the limitations of previous studies and the fact that a growing body of new RCT studies published in Chinese and English language is investigating the effect of exercise on cognition and ADL in populations with AD.…”

Understanding How Physical Exercise Improves Alzheimer’s Disease: Cholinergic and Monoaminergic Systems

“…In THY-Tau22 mice, long-term voluntary wheel running for 9 months reversed pathological reduction of ChAT + neurons in the MS-DB; this was accompanied by improvements in tau pathology and neuroinflammation within the hippocampus ( Belarbi et al, 2011 ). Moreover, where comparisons were possible, the effect size for exercise was generally comparable with that of donepezil ( Pisani et al, 2021 ). In Aβ 25–35 -induced rats, both chronic aerobic and resistance exercise have similar effects to those of AChEIs, reducing AChE activity and reversing recognition memory deficits ( Farzi et al, 2019 ).…”

An Overview of the Evidence and Mechanism of Drug–Herb Interactions Between Propolis and Pharmaceutical Drugs

“…As the most common cause of dementia, Alzheimer’s disease is characterized by progressive and irreversible cognitive and memory loss, affecting an increasing population of the elderly worldwide ( Pisani, Mueller, 2021 ). Remarkably, recent studies have shown that people with mild cognitive impairment, although is normal in aging, have a three to five times higher risk of developing dementia, especially Alzheimer’s disease ( Bennett, Wilson, 2002 ).…”