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Background: Frequent cognitive activity in old age has been associated with reduced risk of Alzheimer disease (AD), but the basis of the association is uncertain.

Methods: More than 700 old people underwent annual clinical evaluations for up to 5 years. At baseline, they rated current and past frequency of cognitive activity with the current activity measure administered annually thereafter. Those who died underwent a uniform postmortem examination of the brain. Amyloid burden, density of tangles, and presence of Lewy bodies were assessed in eight brain regions and the number of chronic cerebral infarctions was noted.

Results: During follow-up, 90 people developed AD. More frequent participation in cognitive activity was associated with reduced incidence of AD (HR = 0.58; 95% CI: 0.44, 0.77); a cognitively inactive person (score = 2.2, 10th percentile) was 2.6 times more likely to develop AD than a cognitively active person (score = 4.0, 90th percentile). The association remained after controlling for past cognitive activity, lifespan socioeconomic status, current social and physical activity, and low baseline cognitive function. Frequent cognitive activity was also associated with reduced incidence of mild cognitive impairment and less rapid decline in cognitive function. Among 102 persons who died and had a brain autopsy, neither global nor regionally specific measures of neuropathology were related to level of cognitive activity before the study, at study onset, or during the course of the study.

Conclusion: Level of cognitively stimulating activity in old age is related to risk of developing dementia.

GLOSSARY: AD = Alzheimer disease; MCI = mild cognitive impairment.

(C)2007 American Academy of Neurology