Midlife activity predicts risk of dementia in older male twin pairs

Alzheimers Dement. 2008 Sep;4(5):324-31. doi: 10.1016/j.jalz.2008.07.002.


Background: This was a prospective study of dementia to elucidate mechanisms of disease risk factors amenable to modification and specifically to determine whether midlife cognitive and physical leisure activities are associated with delayed onset or reduced risk of dementia within older male twin pairs.

Methods: The co-twin control design used prospectively collected exposure information to predict risk of dementia 20 to 40 years later. The subjects were community-dwelling and nursing home residents living throughout the continental United States. We studied 147 male twin-pairs who were discordant for dementia or age of dementia onset and were members of the National Academy of Sciences-National Research Council Twin Registry of World War II veterans and participants in the Duke Twins Study of Memory in Aging. The main outcome measure was diagnosed dementia by using a two-stage screen and full clinical evaluation. Conditional odds ratios were estimated for the association between midlife leisure activities and late-life dementia.

Results: Greater midlife cognitive activity was associated with a 26% risk reduction for dementia onset. Protective effects were most robust in monozygotic twin pairs, where genetic and early-life influences were most tightly controlled, and for activities that were often cognitive and social in nature. Cognitive activity was particularly protective among monozygotic twin pairs carrying the apolipoprotein E epsilon4 allele, with a 30% risk reduction. Midlife physical activity did not modify dementia risk.

Conclusions: Participation in a range of cognitively and socially engaging activities in midlife reduced risk for dementia and AD in twins discordant for onset, particularly among twin pairs at elevated genetic risk, and might be indicative of an enriched environment.

Publication types

  • Research Support, N.I.H., Extramural
  • Twin Study

MeSH terms

  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Apolipoprotein E4 / genetics
  • Cognition / physiology*
  • Dementia / epidemiology*
  • Dementia / genetics
  • Diseases in Twins / epidemiology*
  • Diseases in Twins / genetics
  • Humans
  • Leisure Activities
  • Male
  • Middle Aged
  • Motor Activity
  • Risk Factors
  • Thinking / physiology*
  • Twins, Monozygotic


  • Apolipoprotein E4