APOE and ACE polymorphisms and dementia risk in the older population over prolonged follow-up: 10 years of incidence in the MRC CFA Study

Background: dementia risk conferred by apolipoprotein-E (APOE) and angiotensin-1-converting enzyme (ACE) polymorphisms have been reported for the MRC Cognitive Function and Ageing Study (CFAS) at 6-year follow-up. We concentrate on incident dementia risk over 10 years. Methods: participants come from MRC CFAS, a multi-centre longitudinal population-based study of ageing in England and Wales. Three follow-up waves of data collection were used: 2, 6 and 10 years. Logistic regressions were undertaken to investigate associations between APOE (n = 955) and ACE (n = 856) alleles/genotypes and incident dementia. Two types of control groups were used: non-demented and highly functioning non-demented. Results were back-weighted. Results: compared to APOE ε3, ε2 conferred protection of odds ratio (OR) = 0.3 (95% confidence interval, CI = 0.1–0.6) and ε4 risk of OR = 2.9 (95% CI = 1.7–4.9) for incident dementia. Compared to ε3/ε3, the ε3/ε4 and ε4/ε4 genotypes conferred risks of OR = 3.6 (95% CI = 1.8–7.3) and OR = 7.9 (95% CI = 1.6–39.2), respectively. The ε3/ε2 genotype protected against dementia (OR = 0.2, 95% CI = 0.1–0.7), and ε2/ε2 had a similar protective effect but with wide CIs (OR = 0.3, 95% CI = 0.1–1.7). Restricting the control group accentuated these differentials. The effects of ACE alleles/genotypes on incident dementia risk were small. Conclusions: APOE but not ACE is associated with late-onset incident dementia in the population. Using longer term follow-up with proper adjustment for attrition and incident cases increases estimates of risk.