Abstract
The extent to which the effect of risk factors on cognitive ageing is dependent on APOE ε4 remains unclear. The objective of this study is to examine whether APOE ε4 allele modifies the association between health behaviors and cognition in late midlife. Data are drawn from 5447 participants of the Whitehall II study, health behaviors were assessed in 1997-1999 (mean age = 55.6, Standard Deviation (SD) = 6.0) and APOE genotype and cognitive function in 2002-2004 (mean age = 60.9, SD = 5.9). Among APOE ε4 non-carriers, current smokers had lower scores on memory (difference in T-score = -2.49, 95%CI: -3.37, -1.60), reasoning (-2.88, 95%CI: -3.74, -2.01), phonemic (-2.66, 95%CI: -3.56, -1.76) and semantic (-2.38, 95%CI: -3.28, -1.47) fluency compared to never smokers. In APOE ε4 carriers, difference between current and never smokers was seen only for reasoning (-1.92, 95%CI: -3.31, -0.51). Interaction terms supported differential effects of smoking as a function of APOE ε4 status for memory (p = 0.01), and phonemic (p = 0.008) and semantic fluency (p = 0.02). Cognitive scores were lower among non-drinkers compared to moderate drinkers, among the sedentary participants and those who ate fruits and vegetable less than 2 times per day irrespective of APOE ε4 status. This study suggests that the APOE ε4 allele modifies the association of smoking but not that of other health behaviors - alcohol consumption, physical activity, fruit and vegetable consumption - with cognitive function in late midlife.
Highlights
The extent to which the effect of risk factors on cognitive ageing is dependent on apolipoprotein E (APOE) ε4 remains unclear
Carriers of the apolipoprotein E (APOE) ε4 allele are at increased risk of late onset Alzheimer's disease [1]
Adverse health behaviors are risk factors for impaired cognition and dementia [5,7]; a recent review concluded that more research is needed to confirm or refute the hypothesis of a differential effect of health behaviors among APOE ε4 carriers [7]
Summary
The extent to which the effect of risk factors on cognitive ageing is dependent on APOE ε4 remains unclear. It has been suggested that, in addition to these direct associations, APOE ε4 might influence cognition indirectly by modifying the effect of non-genetic risk factors, such as health behaviors, on cognitive ageing [5,6]. The difference in mean cognitive Tscore, as well as the 95% confidence intervals (CI), adjusted for age and sex, was calculated across health behavior categories separately for APOE ε4 non-carriers and carriers.
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