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

  • 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 andObjective: 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).show moreshow less

Export metadata

Additional Services

Share in Twitter Search Google Scholar Statistics
Metadaten
Author:Andreas Stroehle, Dietlinde K. Schmidt, Florian Schultz, Nina Fricke, Theresa Staden, Rainer Hellweg, Josef Priller, Michael Armin RappORCiDGND, Nina Rieckmann
DOI:https://doi.org/10.1016/j.jagp.2015.07.007
ISSN:1064-7481 (print)
ISSN:1545-7214 (online)
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=26601726
Parent Title (English):The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry
Publisher:Elsevier
Place of publication:New York
Document Type:Article
Language:English
Year of first Publication:2015
Year of Completion:2015
Release Date:2017/03/27
Tag:Alzheimer dementia; drug; exercise; mild cognitive impairment
Volume:23
Issue:12
Pagenumber:16
First Page:1234
Last Page:1249
Funder:German Federal Ministry of Education and Research; European Commission; Lundbeck; Stifterverband fur die Deutsche Wissenschaft; Berlin Brandenburgische Akademie der Wissenschaften; Boehringer Ingelheim Fonds; Pfizer; Eli Lilly International Foundation; BMBF; Deutsche Forschungsgemeinschaft; Hirnliga; Merz; Novartis; German Research Foundation; German Center for Neurodegenerative Diseases; Berlin Institute of Health
Organizational units:Humanwissenschaftliche Fakultät / Institut für Sportmedizin und Prävention
Peer Review:Referiert