Apolipoprotein E genotype, vascular risk and early cognitive impairment in an African Caribbean population

A reduced risk of Alzheimer's disease (AD) associated with the apolipoprotein E (APOE) epsilon4 allele is reported in populations of African origin. In order to clarify possible reasons for this, we examined the association between APOE genotype and early cognitive impairment in a community-based African Caribbean UK population aged 55-75 years. APOE genotype was available for 202 participants, 57 (28%) of whom were classified as having relative cognitive impairment on a battery of neuropsychological tests. Cognitive impairment was negatively associated with epsilon2 and positively but more weakly associated with epsilon4. Effects of both alleles increased markedly after age 70. The effect of epsilon4 was increased in combination with hypertension, diabetes or lower educational attainment, but these factors did not influence epsilon2 effects. Cholesterol and triglyceride levels partially explained effects of epsilon2, but did not account for those of epsilon4. A reduced association between epsilon4 and later AD in populations of African origin is unlikely to be explained by reduced cognitive effects or by differential mortality. However, it may be accounted for by vascular comorbidity. The different patterns of association between epsilon2 and epsilon4 alleles suggest different pathways of effect.