PATTERNS OF RISK IN FIRST-DEGREE RELATIVES OF PATIENTS WITH ALZHEIMERS-DISEASE

Background: Although an increased cumulative risk for primary progress ive dementia (PPD) has been repeatedly demonstrated in relatives of pr obands with Alzheimer's disease (AD), an examination of their rates of illness at different ages has not been previously undertaken. Such an examination might reveal possible age-related characteristics associa ted with a more familial variety of AD. Methods: Using family history interviews and survival analysis, the cumulative risk for and 5-year a ge-specific hazard rates of PPD were assessed in the first-degree rela tives of 200 probands with AD and two nondemented control groups-179 e lderly ascertained through the Alzheimer's Disease Research Center (AD RC-derived controls) and 427 elderly ascertained from community senior centers (community controls). Results: The PPD risk curve for the rel atives of probands with AD rose to about 30% and was significantly hig her than the curves for the relatives of the ADRC-derived and communit y controls, where comparable rates were observed (approximately 12%). The age-specific hazard rates of PPD were calculated in three groups o f relatives for each 5-year interval from ages 45 to 49 years through ages 85 to 89 years. The age-specific relative risk (RR(i)) for PPD in the relatives of probands with AD began to steadily diminish from the 75- to 79-year age interval (RR(i)=13.49) through the 85- to 89-year age interval (RR(i)=0.96) compared with the relatives of ADRC-derived controls and from the 60- to 64-year age interval (RR(i)=16.15) throug h the 85- to 89-year age interval (RR(i)=2.03) compared with the relat ives of the community controls. Conclusions: These data indicate that, for relatives of probands with AD, while the lifetime risk for PPD is greater than in relatives of controls, the familial contribution to t he risk for PPD decreases with increasing age. The higher risk for PPD in relatives of probands with AD may be substantially diminished or e ven eliminated by the latter half of the ninth decade.