Apolipoprotein E Phenotypes, Dementia and Mortality in a Prospective Population Sample

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Abstract
OBJECTIVE: To study the relationships between apoE phenotypes, dementia, and mortality. SETTING: A population‐based study in Helsinki, Finland (the Helsinki Ageing Study). DESIGN: A prospective birth cohort study with 5‐year follow‐up. PARTICIPANTS: A total of 550 subjects of three birth cohorts of 75 (n = 182), 80 (n = 185), and 85 (n = 183) years of age. MEASUREMENTS: ApoE phenotype was determined from baseline blood samples. The cognitive function of the subjects was tested at baseline and at a 5‐year follow‐up using the Mini‐Mental State Examination (MMSE) and the Clinical Dementia Rating (CDR). Diagnosis and type of dementia were determined by a neurologist. The cohorts were followed for 5 years, and causes of death were determined. Cox proportional hazards model was used for survival analyses. Analyses were performed comparing the apoE e4 allele and others. RESULTS: At baseline, the apoE e4 allele was found in 148 of 550 subjects (27%), in 24% of nondemented persons, in 51% of patients with probable or uncertain Alzheimer's disease (AD), and in 34% patients with vascular dementia. The CDR score was worse among subjects with an e4 allele compared with others at baseline (P < .001) and after a 5‐year follow‐up (P = .007). The crude mortality rates of subjects with and without an e4 allele were 48% (n = 71) and 37% (n = 148), respectively. After controlling for age and gender, the hazard ratio of an e4 allele was 1.61 (95% CI, 1.21–2.14) for all‐cause mortality, deaths caused by dementia 2.20 (95% CI, 1.03–4.72), and presence of AD 3.24 (95% CI, 1.67–6.25). CONCLUSIONS: In a population aged 75 to 85 years, the presence of an apoE e4 allele is associated with impaired cognitive function, clinical dementia, AD, and excess 5‐year mortality resulting from dementia and all causes.