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Neurology. 2019 Apr 9;92(15):e1745-e1753. doi: 10.1212/WNL.0000000000007231. Epub 2019 Mar 13.

Relative risk for Alzheimer disease based on complete family history.

Author information

1
From the Genetic Epidemiology Program, Department of Internal Medicine (L.A.C.-A., J.M.F., C.C.T., H.K.), Center for Alzheimer's Care, Imaging and Research, Department of Neurology (N.L.F.), and Department of Family and Preventive Medicine (K.S.), University of Utah School of Medicine; Huntsman Cancer Institute (L.A.C.-A., H.K.); George E. Wahlen Department of Veterans Affairs Medical Center (L.A.C.-A.), Salt Lake City; Department of Psychology (J.T., C.C.), Utah State University, Logan; and Departments of Biology and Neuroscience (J.S.K.K.), Brigham Young University, Provo, UT. lisa.albright@utah.edu.
2
From the Genetic Epidemiology Program, Department of Internal Medicine (L.A.C.-A., J.M.F., C.C.T., H.K.), Center for Alzheimer's Care, Imaging and Research, Department of Neurology (N.L.F.), and Department of Family and Preventive Medicine (K.S.), University of Utah School of Medicine; Huntsman Cancer Institute (L.A.C.-A., H.K.); George E. Wahlen Department of Veterans Affairs Medical Center (L.A.C.-A.), Salt Lake City; Department of Psychology (J.T., C.C.), Utah State University, Logan; and Departments of Biology and Neuroscience (J.S.K.K.), Brigham Young University, Provo, UT.

Abstract

OBJECTIVE:

The inherited component for Alzheimer disease (AD) risk has focused on close relatives; consideration of the full family history may improve accuracy and utility of risk estimates.

METHODS:

A population resource including a genealogy of Utah pioneers from the 1800s linked to Utah death certificates was used to estimate relative risk for AD based on specific family history constellations, including from first- to third-degree relatives.

RESULTS:

Any affected first-degree relatives (FDR) significantly increased risk of AD (≥1 FDRs: relative risk [RR] 1.73, 95% confidence interval [CI] [1.59-1.87]; ≥2 FDRs: RR 3.98 [3.26-4.82]; ≥3 FDRs: RR 2.48 [1.07-4.89]; ≥4 FDRs: RR 14.77 [5.42-32.15]). Affected second-degree relatives (SDR) increased risk even in the presence of affected FDRs (FDR = 1 with SDR = 2: RR 21.29 [5.80-54.52]). AD only in third-degree relatives (TDR) also increased risk (FDR = 0, SDR = 0, TDR ≥3: RR 1.43 [1.21-1.68]). Mixed evidence was observed for differences in risk based on maternal compared to paternal inheritance; higher risks for men than women with equivalent family history, and higher risk for individuals with at least one affected FDR regardless of the relative's age at death, were observed.

CONCLUSIONS:

This population-based estimation of RRs for AD based on family history ascertained from extended genealogy data indicates that inherited genetic factors have a broad influence, extending beyond immediate relatives. Providers should consider the full constellation of family history when counseling patients and families about their risk of AD.

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