Drug and Exercise Treatment of Alzheimer Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis of Effects on Cognition in Randomized Controlled Trials

Andreas Ströhle, Dietlinde K Schmidt, Florian Schultz, Nina Fricke, Theresa Staden, Rainer Hellweg, Josef Priller, Michael A Rapp, Nina Rieckmann

Research output: Contribution to journalReview articlepeer-review

Abstract

OBJECTIVE: Demographic changes are increasing the pressure to improve therapeutic strategies against cognitive decline in Alzheimer disease (AD) and mild cognitive impairment (MCI). Besides drug treatment, physical activity seems to be a promising intervention target as epidemiological and clinical studies suggest beneficial effects of exercise training on cognition. Using comparable inclusion and exclusion criteria, we analyzed the efficacy of drug therapy (cholinesterase inhibitors, memantine, and Ginkgo biloba) and exercise interventions for improving cognition in AD and MCI populations.

METHODS: We searched The Cochrane Library, EBSCO, OVID, Web of Science, and U.S Food and Drug Administration data from inception through October 30, 2013. Randomized controlled trials in which at least one treatment arm consisted of an exercise or a pharmacological intervention for AD or MCI patients, and which had either a non-exposed control condition or a control condition that received another intervention. Treatment discontinuation rates and Standardized Mean Change score using Raw score standardization (SMCR) of cognitive performance were calculated.

RESULTS: Discontinuation rates varied substantially and ranged between 0% and 49% with a median of 18%. Significantly increased discontinuation rates were found for galantamine and rivastigmine as compared to placebo in AD studies. Drug treatments resulted in a small pooled effect on cognition (SMCR: 0.23, 95% CI: 0.20 to 0.25) in AD studies (N = 45, 18,434 patients) and no effect in any of the MCI studies (N = 5, 3,693 patients; SMCR: 0.03, 95% CI: 0.00 to 0.005). Exercise interventions had a moderate to strong pooled effect size (SMCR: 0.83, 95% CI: 0.59 to 1.07) in AD studies (N = 4, 119 patients), and a small effect size (SMCR: 0.20, 95% CI: 0.11 to 0.28) in MCI (N = 6, 443 patients).

CONCLUSIONS: Drug treatments have a small but significant impact on cognitive functioning in AD and exercise has the potential to improve cognition in AD and MCI. Head-to-head trials with sufficient statistical power are necessary to directly compare efficacy, safety, and acceptability. Combining these two approaches might further increase the efficacy of each individual intervention.

IDENTIFIER: PROSPERO (2013:CRD42013003910).

Original languageEnglish
Pages (from-to)1234-1249
Number of pages16
JournalAmerican Journal of Geriatric Psychiatry
Volume23
Issue number12
Early online date21 Jul 2015
DOIs
Publication statusE-pub ahead of print - 21 Jul 2015

Keywords

  • Alzheimer Disease
  • Cognition
  • Cognitive Dysfunction
  • Exercise Therapy
  • Humans
  • Randomized Controlled Trials as Topic
  • Treatment Outcome
  • Journal Article
  • Meta-Analysis
  • Review

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