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Jeremy M. Silverman, PhD; Christopher J. Smith, MA; Deborah B. Marin, MD; Richard C. Mohs, PhD; Cathi B. Propper, BA

Arch Gen Psychiatry. 2003;60:190-197.

Background  The incidence of Alzheimer disease (AD) peaks after 85 years of age. Although genetic factors are implicated in AD with substantially earlier onset, the familial characteristics of high-incidence very late-onset AD (VLOAD, defined here as AD with onset age 85 years) remain unknown.

Methods  We collected information pertaining to the cognitive status and demographics of 809 parents and siblings of 144 VLOAD probands, 4235 parents and siblings of 793 earlier-onset AD probands, and 7646 parents and siblings of 1493 nondemented elderly probands. Cumulative risks and 5-year interval-specific hazard rate ratios were calculated for AD in relatives of the 2 AD proband groups and relatives of the nondemented elderly group.

Results  The cumulative risk for AD in the relatives of VLOAD probands was significantly different than that in the relatives of earlier-onset AD probands (P<.001), but not in the relatives of nondemented elderly probands. Also, the relatives of earlier-onset AD probands had hazard rate ratios ranging from 19.7 in those aged 50 to 54 years to 1.2 in those aged 90 to 94 years. Rates successively dropped as age intervals increased.

Conclusions  At least through the middle of the ninth decade of life, relatives of VLOAD probands have a lower risk for AD than those of earlier-onset AD probands. In addition, the relatively increased risk of relatives of earlier-onset AD probands is highest at younger ages and diminishes with increasing age. In counseling family members of patients with AD concerned about their own risk, the onset age of the patient and the age of the concerned relative should be considered. Very late-onset AD may be a good target for investigating environmental factors associated with AD.

From the Department of Psychiatry, Mount Sinai School of Medicine, New York, NY (Drs Silverman, Marin, and Mohs, Mr Smith, and Ms Propper), and the General Medical Research Service, Veterans Affairs Medical Center, Bronx, NY (Drs Silverman and Mohs, Mr Smith, and Ms Propper).

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