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Longitudinal analysis of the effect of apolipoprotein E ε4 and education on cognitive performance in elderly subjects: the PAQUID study

Background: The apolipoprotein E (apoE) ε4 allele has been shown to be a risk factor for dementia, but it is not clear to what extent apoE affects overall cognitive function in non-demented elderly subjects, or how this risk may be modified by gene–environment interactions. Objective: To examine changes in cognitive function in elderly people as a function of the apoE ε4 phenotype. Methods: A community based prospective cohort study of 600 non-demented subjects aged over 65 years living in Gironde (France) was analysed to evaluate change over time (seven years) in scores on the mini-mental state examination (MMSE). Results: Age at cohort inception was negatively associated with cognitive performance for both ε4 carriers and non-carriers (p < 0.001). The evolution of MMSE scores differed as a function of age: scores remained stable among younger subjects but decreased over time in older subjects. The ε4 allele was shown to be significantly associated with lower cognitive performance at baseline (p = 0.02). The course of cognitive performance during the follow up was the same for both ε4 carriers and non-carriers. Lower educational level was associated with lower cognitive performance at baseline (p < 0.001) and the effect of an ε4 allele on cognitive performance disappeared after adjustment for education. When incident cases of dementia were excluded, the results were unchanged except for the course of the MMSE scores, which now remained stable over time in the older subjects. Conclusions: apoE ε4 carriers show decreased MMSE scores compared with ε4 non-carriers, but the effect of apoE on cognition disappears after adjustment for education. Non-demented elderly people maintain a stable cognitive performance regardless of their apoE phenotype.