The Role of APOE ∊4 in Modulating Effects of Other Risk Factors for Cognitive Decline in Elderly Persons

Abstract

The influence of cardiovascular diseases (CVDs) and risk factors on cognitive decline in the elderly is of importance in the search for predictors and pathways for prevention of dementia. Previous work has linked cognitive decline and dementia to CVD,¹ stroke,² diabetes mellitus (DM) and glucose metabolism,^2-11 hypertension and high and low blood pressure,^2,12-17 peripheral vascular disease,¹⁸ atherosclerosis,¹⁹ genetic factors,^20,21 and cerebral blood flow.^22,23 Apolipoprotein E ∊4 (APOE ∊4) genotype is associated with an increased risk of dementia and cognitive decline.²⁴ Apolipoprotein E ∊4 alleles may account for 13% to 20% of dementia cases.^25,26 Although APOE genotype is not a specific disease locus, it may create host susceptibility that affects the rate of disease progression.²⁷ Gene-environment interactions are important in the progression of cognitive impairment and the development of dementia.²⁸ Recent work by the Rotterdam Study¹ has suggested that DM, peripheral vascular disease, and atherosclerosis are associated with an increased risk of vascular dementia and Alzheimer disease (AD). Similar findings for a synergistic role played by the APOE ∊4 genotype in the presence of atherosclerotic diseases have been reported by Kuusisto et al.²⁹