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

Lookup NU author(s): Professor Ian McKeith, Professor Carol Brayne


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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 epsilon 3, epsilon 2 conferred protection of odds ratio (OR) = 0.3 (95% confidence interval, CI = 0.1-0.6) and epsilon 4 risk of OR = 2.9 (95% CI = 1.7-4.9) for incident dementia. Compared to epsilon 3/epsilon 3, the epsilon 3/epsilon 4 and epsilon 4/epsilon 4 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 epsilon 3/epsilon 2 genotype protected against dementia (OR = 0.2, 95% CI = 0.1-0.7), and epsilon 2/epsilon 2 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.

Publication metadata

Author(s): Keage HAD, Matthews FE, Yip A, Gao L, McCracken C, McKeith IG, Rubinsztein DC, Brayne C, MRC Cognitive Function Ageing Stud

Publication type: Article

Publication status: Published

Journal: Age and Ageing

Year: 2010

Volume: 39

Issue: 1

Pages: 104-111

ISSN (print): 0002-0729

ISSN (electronic): 1468-2834

Publisher: Oxford University Press


DOI: 10.1093/ageing/afp210


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Funder referenceFunder name
Health Department
Marie Curie International Incoming Fellowship
Wellcome Trust
G990140Medical Research Council
RHAG/094BUPA Foundation