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Multicenter Study
. 2010 Jan;39(1):104-11.
doi: 10.1093/ageing/afp210. Epub 2009 Nov 24.

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

H A D Keage  1 , F E Matthews, A Yip, L Gao, C McCracken, I G McKeith, D C Rubinsztein, C Brayne; MRC Cognitive Function and Ageing Study
Affiliations
Multicenter Study

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

H A D Keage et al. Age Ageing. 2010 Jan.

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 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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Figures

Figure 1
Figure 1
An illustration of the MRC CFAS study design and the number of participants seen at each screen/assessment relative to the four centres used in the current study. The grey shading indicates assessments that were used to define cases of incident dementia.
See this image and copyright information in PMC

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