A randomized controlled trial of multicomponent exercise in older adults with mild cognitive impairment

PLoS One. 2013 Apr 9;8(4):e61483. doi: 10.1371/journal.pone.0061483. Print 2013.


Background: To examine the effect of multicomponent exercise program on memory function in older adults with mild cognitive impairment (MCI), and identify biomarkers associated with improvement of cognitive functions.

Methodology/principal findings: Subjects were 100 older adults (mean age, 75 years) with MCI. The subjects were classified to an amnestic MCI group (n = 50) with neuroimaging measures, and other MCI group (n = 50) before the randomization. Subjects in each group were randomized to either a multicomponent exercise or an education control group using a ratio of 1∶1. The exercise group exercised for 90 min/d, 2 d/wk, 40 times for 6 months. The exercise program was conducted under multitask conditions to stimulate attention and memory. The control group attended two education classes. A repeated-measures ANOVA revealed that no group × time interactions on the cognitive tests and brain atrophy in MCI patients. A sub-analysis of amnestic MCI patients for group × time interactions revealed that the exercise group exhibited significantly better Mini-Mental State Examination (p = .04) and logical memory scores (p = .04), and reducing whole brain cortical atrophy (p<.05) compared to the control group. Low total cholesterol levels before the intervention were associated with an improvement of logical memory scores (p<.05), and a higher level of brain-derived neurotrophic factor was significantly related to improved ADAS-cog scores (p<.05).

Conclusions/significance: The results suggested that an exercise intervention is beneficial for improving logical memory and maintaining general cognitive function and reducing whole brain cortical atrophy in older adults with amnestic MCI. Low total cholesterol and higher brain-derived neurotrophic factor may predict improvement of cognitive functions in older adults with MCI. Further studies are required to determine the positive effects of exercise on cognitive function in older adults with MCI.

Trial registration: UMIN-CTR UMIN000003662 ctr.cgi&quest;function&hairsp;&equals;&hairsp;brows&action&hairsp;&equals;&hairsp;brows&type&hairsp;&equals;&hairsp;summary&recptno&hairsp;&equals;&hairsp;R000004436&language&hairsp;&equals;&hairsp;J.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amnesia / blood
  • Amnesia / pathology
  • Amnesia / physiopathology
  • Amnesia / therapy*
  • Atrophy / blood
  • Atrophy / pathology
  • Atrophy / physiopathology
  • Atrophy / therapy*
  • Attention
  • Biomarkers / blood
  • Brain / pathology
  • Brain / physiopathology*
  • Brain-Derived Neurotrophic Factor / blood
  • Cholesterol / blood
  • Cognition
  • Cognitive Dysfunction / blood
  • Cognitive Dysfunction / pathology
  • Cognitive Dysfunction / physiopathology
  • Cognitive Dysfunction / therapy*
  • Exercise Therapy*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory
  • Neuropsychological Tests


  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • Cholesterol

Grants and funding

This study was supported in part by a grant from the Japanese Ministry of Health, Labour and Welfare (Project for optimizing long-term care; B-3) and a Grant-in-Aid for Scientific Research from the Ministry of Education and Culture of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.