A PROSPECTIVE-STUDY OF COGNITIVE HEALTH IN THE ELDERLY (OREGON BRAIN AGING STUDY) - EFFECTS OF FAMILY HISTORY AND APOLIPOPROTEIN-E GENOTYPE

The oldest old are the fastest-growing segment of our population and h ave the highest prevalence of dementia. Little is known about the gene tics of cognitive health in the very old. The aim of this study was to determine whether the genetic risk factors for Alzheimer disease (AD) -namely, apolipoprotein E (APOE) epsilon 4 allele and a family history of dementia-continue to be important factors in the cognitive health of the very old. Case-control studies suggest that the effect of genet ic factors diminishes at age >75 years. The present prospective study provided evidence to the contrary. We studied 114 Caucasian subjects w ho were physically healthy and cognitively intact at age 75 years and who were followed, for an average of 4 years, with neurological, psych ometric, and neuroimaging examinations. Excellent health at entry did not protect against cognitive decline. Incidence of cognitive decline rose sharply with age. epsilon 4 and a family history of dementia (ind ependent of epsilon 4) were associated with an earlier age at onset of dementia. Subjects who had epsilon 4 or a family history of dementia had a ninefold-higher age-specific risk for dementia than did those wh o had neither epsilon 4 nor a family history of dementia. These observ ations suggest that the rate of cognitive decline increases with age a nd that APOE and other familial/genetic factors influence the onset ag e throughout life.