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Patterns of Risk in First-Degree Relatives of Patients With Alzheimer's Disease

Jeremy M. Silverman, PhD; Ge Li, MD, PhD; Michele L. Zaccario; Christopher J. Smith; James Schmeidler, PhD; Richard C. Mohs, PhD; Kenneth L. Davis, MD
Arch Gen Psychiatry. 1994;51(7):577-586. doi:10.1001/archpsyc.1994.03950070069012.
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Background:  Although an increased cumulative risk for primary progressive dementia (PPD) has been repeatedly demonstrated in relatives of probands 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 associated with a more familial variety of AD.

Methods:  Using family history interviews and survival analysis, the cumulative risk for and 5-year age-specific hazard rates of PPD were assessed in the first-degree relatives of 200 probands with AD and two nondemented control groups—179 elderly ascertained through the Alzheimer's Disease Research Center (ADRC-derived controls) and 427 elderly ascertained from community senior centers (community controls).

Results:  The PPD risk curve for the relatives of probands with AD rose to about 30% and was significantly higher than the curves for the relatives of the ADRCderived and community controls, where comparable rates were observed (approximately 12%). The age-specific hazard rates of PPD were calculated in three groups of relatives for each 5-year interval from ages 45 to 49 years through ages 85 to 89 years. The age-specific relative risk (RR,) for PPD in the relatives of probands with AD began to steadily diminish from the 75- to 79-year age interval (RRi=13.49) through the 85- to 89-year age interval (RRi=0.96) compared with the relatives of ADRCderived controls and from the 60- to 64-year age interval (RRi=16.15) through the 85- to 89-year age interval (RRi=2.03) compared with the relatives 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 the risk for PPD decreases with increasing age. The higher risk for PPD in relatives of probands with AD may be substantially diminished or even eliminated by the latter half of the ninth decade.

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