Role of APOE ε4 Allele and Incident Stroke on Cognitive Decline and Mortality

Background: The apolipoprotein E (APOE) epsilon 4 allele and stroke increase the risk of cognitive decline. However, the association of the APOE epsilon 4 allele before and after stroke is not well understood. Methods: Using a prospective sample of 3444 (66% African Americans, 61% females, mean age = 71.9 y) participants, we examined cognitive decline relative to stroke among those with and without the APOE epsilon 4 allele. Results: In our sample, 505 (15%) had incident stroke. Among participants without stroke, the epsilon 4 allele was associated with increased cognitive decline compared to noncarriers (0.080 vs. 0.036 units/year; P < 0.0001). Among participants without the epsilon 4 allele, cognitive decline increased significantly after stroke compared to before stroke (0.115 vs. 0.039 units/year; P < 0.0001). Interestingly, cognitive decline before and after stroke was not significantly different among those with the epsilon 4 allele (0.091 vs. 0.102 units/year; P = 0.32). Poor cognitive function was associated with higher risk of stroke (hazard ratio = 1.41, 95% confidence interval, 1.25-1.58), but the APOE epsilon 4 allele was not (P = 0.66). The APOE epsilon 4 allele, cognitive function, and incident stroke were associated with mortality. Conclusions: The association of stroke with cognitive decline appears to differ by the presence of the APOE epsilon 4 allele, but no such interaction was observed for mortality.