Key result
APOE epsilon4 allele linked to ~190% greater incident dementia risk vs epsilon3.
Why the study?
Are APOE and ACE polymorphisms associated with incident dementia risk in the older population over 10 years?
Cohort (n=955)
Yes
Are APOE and ACE polymorphisms associated with incident dementia risk in the older population over 10 years?
Odds Ratio: 2.9 (95% CI 1.7–4.9)
APOE polymorphisms, specifically the epsilon4 allele, are strongly associated with an increased risk of late-onset incident dementia over a 10-year follow-up, whereas ACE polymorphisms show little effect.
APOE ε4 may aid risk stratification in older adults; extends genetic associations but should not yet change practice.
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 epsilon3, epsilon2 conferred protection of odds ratio (OR) = 0.3 (95% confidence interval, CI = 0.1-0.6) and epsilon4 risk of OR = 2.9 (95% CI = 1.7-4.9) for incident dementia. Compared to epsilon3/epsilon3, the epsilon3/epsilon4 and epsilon4/epsilon4 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 epsilon3/epsilon2 genotype protected against dementia (OR = 0.2, 95% CI = 0.1-0.7), and epsilon2/epsilon2 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.
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Keage et al. (2009) conducted a cohort in incident dementia (n=955). APOE epsilon4 allele vs. APOE epsilon3 allele was evaluated on incident dementia (OR 2.9, 95% CI 1.7-4.9). The APOE epsilon4 allele was associated with an increased risk of incident dementia over 10 years compared to the epsilon3 allele (OR 2.9; 95% CI 1.7-4.9), whereas ACE polymorphisms had little effect.
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