Association between apolipoprotein E epsilon4 and the rate of cognitive decline in community-dwelling elderly individuals with and without dementia.

To determine whether the apolipoprotein E epsilon4 allele (apoE epsilon4) is associated with cognitive decline in individuals with and without dementia, we conducted a 4-year longitudinal study of subjects with a range of cognitive function. At baseline, respondents (n=511) were randomly selected according to age and Mini-Mental State Examination score from a community-based study of dementia among noninstitutionalized persons aged 65 to 84 years. Respondents were examined at baseline and followed up in 3 annual visits. At baseline, subjects were classified as having normal cognitive function, minimal dementia, or dementia, according to criteria from the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) and the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition. Of the 511 respondents at baseline, 405 who were examined at least 2 times are included in this analysis. Cognitive decline was determined by a slope estimating yearly change in score on the neuropsychological test, the CAMCOG (the cognitive section of the CAMDEX), and its sub-scales of memory and nonmemory functions. Among the subjects who had normal cognitive function at baseline, apoE epsilon4 carriers showed a significantly greater decline (P<.001) in score on the CAMCOG compared with noncarriers. Differences in decline on the memory and nonmemory subtests were also significant (P<.001). Rates of cognitive decline were not related to apoE epsilon4 status in the groups with minimal dementia and dementia. In our community-based sample, apoE epsilon4 was associated with the rate of cognitive decline prior to the clinically symptomatic phase of dementia. Knowing the apoE epsilon4 status of those already symptomatic for dementia may not improve knowledge about a patient's prognosis.