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 ascert
ain the presence of dementia or cognitive impairment. The sample was r
e-interviewed in 1994, when the apoE genotype was also determined. Pre
valence 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 ra
tio for dementia 1.89, 95% confidence interval 1.04-3.44 and for homoz
ygotes OR 3.58, 95% CI 1.82-11.82; both adjusted for age). However, ev
en in subjects homozygous for epsilon 4 the estimated prevalence of de
mentia 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 th
ose with none. This study confirms in a population sample that the eps
ilon 4 allele is a risk factor for dementia, but refutes the suggestio
n that homozygosity for the epsilon 4 allele is sufficient for the dev
elopment of Alzheimer's disease: persons with either one or two epsilo
n 4 alleles may reach late old age without cognitive impairment.