APOE Genotype Modifies the Relationship between Midlife Vascular Risk Factors and Later Cognitive Decline

Background: Vascular risk factors have been associated with cognitive decline; however, it remains unclear whether apolipoprotein E (APOE) genotype modifies this relationship. We aimed to further elucidate these relationships and extend previous findings by examining data from a more comprehensive cognitive assessment than used in prior studies. Methods: In all, 1436 participants from the prospective Framingham Offspring Cohort Study underwent health examination from 1991 to 1995, followed by a baseline neuropsychological assessment (1999-2003) and a repeat neuropsychological assessment approximately 8 years later (2004-2009). Multivariate linear regression analyses were performed to examine the relationship among midlife vascular risk factors, presence of the APOE epsilon 4 allele, and cognitive change. Results: APOE genotype significantly modified the associations between both midlife hypertension and cardiovascular disease and decline in language abilities and midlife diabetes and decline in verbal memory, attention, and visuospatial abilities. Associations between increased midlife vascular risk burden and greater cognitive decline were observed among APOE epsilon 4 carriers but not noncarriers. Conclusions: The present findings revealed a subgroup at increased risk for cognitive decline (APOE epsilon 4 carriers with midlife exposure to vascular risk factors) and suggest that treatment of vascular risk factors during midlife may reduce the risk of cognitive impairment later in life, particularly among APOE epsilon 4 carriers.