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Apolipoprotein E Genotype Modifies the Association between Midlife Lung Function and Cognitive Function in Old Age

Background/Aims: Because poor lung function may be a risk factor for cognitive decline, we aimed to test the association of respiratory function with cognitive function and dementia later in life, as well as potential effect modification by APOE ε4 carrier status. Methods: In a prospective population-based cohort study, forced vital capacity and forced expiratory flow were measured around 1965 in 857 men aged 45–64 years (394 from Finland, 208 from The Netherlands, and 255 from Italy). The Mini-Mental State Examination scores around 1990, 1995 and 2000 were analyzed using multilevel regression models and the Clinical Dementia Rating score around 1990 using multinomial logistic regression analyses. Results: Midlife lung function was positively associated with cognitive function in old age in APOE ε4 non-carriers, but not in carriers (p < 0.05 for interaction). In Finland and Italy, 18.6% had questionable to mild dementia and 2.8% moderate to severe dementia after 25 years of follow-up. Dementia was inversely related to midlife lung function in APOE ε4 non-carriers, but not in carriers (p < 0.05 for interaction). Conclusions: Small lung volumes were prospectively associated with an increased risk for poor cognitive function and dementia in non-carriers of the APOE ε4 gene.