Earlier onset of Alzheimer's disease in men with Down syndrome.

BACKGROUND

Virtually all individuals with Down syndrome (DS) have neuropathologic changes characteristic of Alzheimer's disease (AD) beginning at 40 years of age. Few studies have examined factors that influence age at onset of AD in DS. We investigated whether sex differences in age at onset and risk of AD among adults with DS are similar to those observed in the general population and whether the effect of sex on risk of AD is modified by apolipoprotein E (APOE) genotype.

METHODS

A community-based sample of 111 adults with cytogenetically confirmed DS (34 to 71 years of age) was ascertained through the New York State Developmental Disabilities system. A semistructured interview with caregivers and review of medical records was used to ascertain the presence or absence of AD. APOE genotyping was carried out without knowledge of the subject's medical history or clinical diagnosis.

RESULTS AND CONCLUSIONS

Both male gender and the presence of an APOE epsilon4 allele were associated with an earlier onset of AD. Compared with women, men with DS were three times as likely to develop AD. Compared with those with the APOE 3/3 genotype, adults with DS with the 3/4 or 4/4 genotypes were four times as likely to develop AD. No individual with an APOE epsilon2 allele developed AD. No evidence of interaction of sex and APOE genotype was found in risk of AD. The higher risk of AD in men may be related to differences in hormonal function between men and women with DS that are distinct from those in the general population.