The E*4 allele of the apolipoprotein E (APOE) gene on chromosome 19 has
been shown to be an age- and dose-related risk factor for Alzheimer's
disease. Of 870 elderly women participating in an osteoporosis study, 13
were previously found to be homozygous for the APOE*4 allele; 1 was
deceased and the rest were assessed for dementia in a "piggyback" study
of dementia. One had moderate [clinical dementia rating (CDR = 2], 2 had
mild dementia (CDR = 1), and 2 had possible dementia (CDR = 0.5). All 3
women over 80 years were definitely demented (CDR > or = 1). Typically,
genetic studies of Alzheimer's and other dementias require the
identification and diagnosis of large numbers of demented subjects, at
considerable expense, followed by genotyping or phenotyping with a
relatively low yield of individuals with rare alleles. We demonstrate a
more cost-effective approach in which the population is first phenotyped
and then stratified by phenotype, so that diagnostic evaluation can be
restricted to individuals with the phenotype of interest.