How can elderly apolipoprotein E ε4 carriers remain free from dementia?

Apolipoprotein E (APOE) epsilon 4 is a major risk factor for Alzheimer's disease (AD) and dementia, but not all epsilon 4 carriers develop dementia. We sought to identify factors that may play a role in modifying the risk of dementia due to epsilon 4. A cognitively intact cohort (n = 932, age >= 75) was followed for 9 years to detect incident dementia cases. At baseline, information on education, leisure activities, and vascular risk factors was collected, and APOE was genotyped. During the follow-up, 324 subjects developed dementia, including 247 AD cases. The hazard ratio (HR, 95% confidence interval [95% CI]) of dementia related to the epsilon 4 was 1.39 (1.11-1.76), while the risk was reduced when epsilon 4 carriers had high education, no vascular risk factors, or high score of leisure activities. Among epsilon 4 carriers, the multiadjusted HRs of dementia that were associated with high education, high level of leisure activities, and absence of vascular risk factors were 0.59 (0.40-0.87), 0.49 (0.29-0.85), and 0.61 (0.41-0.90), respectively. The epsilon 4 carriers with these factors had about 1.2 years delayed time to dementia onset compared with those without these factors. High education, active leisure activities, or maintaining vascular health seems to reduce the risk of dementia related to APOE epsilon 4. The epsilon 4 carriers with these characteristics appear to have similar dementia-free survival time to non-epsilon 4 carriers. (C) 2013 Elsevier Inc. All rights reserved.