A gender difference in the association between APOE genotype and age-related cognitive decline.

OBJECTIVE: To determine whether the APOE epsilon4 allele is associated with age-related intellectual decline in a community-dwelling sample of Danes.

METHODS: A sample of 189 subjects who did not have dementia was tested with the Wechsler Adult Intelligence Scale (WAIS) at the ages of 50 and 80 years. Of these subjects, 163 (84 women and 79 men) completed all WAIS subtests at both assessments and 139 completed the digit symbol and block design subtests at the ages of 50, 60, 70, and 80 years.

RESULTS: Cognitive decline from the age of 50 to the age of 80 years was substantial and larger for the performance subtests than for the verbal subtests (the declines were 18.40 for the performance IQ and 8.39 for the verbal IQ). APOE genotype was unrelated to the observed WAIS results of the 80-year assessment, but there was a significant interaction between APOE genotype and sex for decline scores in the performance IQ and three performance subtests (digit symbol, block design, and object assembly). In women, 26 epsilon4 carriers showed larger decline than 58 noncarriers, whereas there was no significant relation between APOE genotype and cognitive decline in men. The association in women between APOE genotype and cognitive decline was significant only for decline in the decade from age 70 to age 80 years. The interaction between sex and APOE genotype remained significant when education was included as a covariate.

CONCLUSION: The APOE epsilon4 allele is associated with normal age-related decline in cognitive functions in women only. This finding may be supportive of recent evidence suggesting sex differences in APOE-associated risk for AD. Thus, the sex difference in the risk of sporadic AD may partly be explained by a sex-specific impact of the APOE epsilon4 allele on age-related cognitive decline.