APOLIPOPROTEIN-E ALLELE EPSILON-4, DEMENTIA, AND COGNITIVE DECLINE IN A POPULATION-SAMPLE

From clinically based series it has been proposed that, in homozygotes for the apolipoprotein E epsilon 4 (apoE epsilon 4) allele, Alzheimer's disease is almost inevitable by the age of 80. A population sample of persons aged 70 years and over was interviewed in 1990-91 to ascertain the presence of dementia or cognitive impairment. The sample was re-interviewed in 1994, when the apoE genotype was also determined. Prevalence data for the 638 persons who completed the second examination revealed a linear association between having an apoE epsilon 4 allele and both dementia and cognitive impairment (for heterozygotes, odds ratio for dementia 1.89, 95% confidence interval 1.04-3.44 and for homozygotes OR 3.58, 95% CI 1.82-11.82; both adjusted for age). However, even in subjects homozygous for epsilon 4 the estimated prevalence of dementia by age 90 was only about 50%. Persons with one or two epsilon 4 alleles were more likely to have a family history of dementia than those with none. This study confirms in a population sample that the epsilon 4 allele is a risk factor for dementia, but refutes the suggestion that homozygosity for the epsilon 4 allele is sufficient for the development of Alzheimer's disease: persons with either one or two epsilon 4 alleles may reach late old age without cognitive impairment.