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

Keage, H. A.D.; Matthews, F. E.; Yip, A.; Gao, L.; McCracken, C.; McKeith, I. G.; Rubinsztein, D. C.; Brayne, C.

Abstract

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. © The Author 2009. Published by Oxford University Press on behalf of the British Geriatrics Society.

Citation

Keage, H. A., Matthews, F. E., Yip, A., Gao, L., McCracken, C., McKeith, I. G., …Brayne, C. (2009). APOE and ACE polymorphisms and dementia risk in the older population over prolonged follow-up: 10 years of incidence in the MRC CFA study. Age and ageing, 39(1), 104-111. https://doi.org/10.1093/ageing/afp210

• Journal Article Type: Article
• Publication Date: Nov 24, 2009
• Deposit Date: Dec 8, 2023
• Journal: Age and Ageing
• Print ISSN: 0002-0729
• Electronic ISSN: 1468-2834
• Publisher: Oxford University Press
• Volume: 39
• Issue: 1
• Pages: 104-111
• DOI: https://doi.org/10.1093/ageing/afp210
• Public URL: https://hull-repository.worktribe.com/output/4455096