Association of Acquired and Heritable Factors With Intergenerational Differences in Age at Symptomatic Onset of Alzheimer Disease Between Offspring and Parents With Dementia

• Type of Material: Article
• Authors: Gregory S. Day, Washington University in St. Louis; Carlos Cruchaga, Washington University in St. Louis; Thomas Wingo, Emory University; Suzanne E. Schindler, Washington University in St. Louis; Dean Coble, Washington University in St. Louis; John C. Morris, Washington University in St. Louis
• Language: English
• Date: 2019-10-01
• Publisher: JAMA Network
• Publication Version: Final Published Version
• Copyright Statement: 2019 Day GS et al. JAMA Network Open.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1001/jamanetworkopen.2019.13491
• Title of Journal or Parent Work: JAMA Network Open
• Volume: 2
• Issue: 10
• Grant/Funding Information: Study funding was provided through a grant paid to Knight ADRC (P50 AG05681) from NIA with additional support from grants from NIH (P01AG003991 and P01AG026276).
• Keywords: acquired factors; intergenerational difference; family history; Alzheimer disease; heritable factors; dementia; early onset; genetics; age at symptomatic onset
• Research Categories: Psychology, Clinical; Biology, Genetics

Abstract

Question What are the associations of acquired and heritable factors with intergenerational differences in age at symptomatic onset (AAO) of Alzheimer disease (AD) among offspring of parents with AD? Findings In this cohort study including 164 participants with symptomatic AD and a parental history of dementia, the factors of parental inheritance, more years of education, and retrospective determination of AAO were associated with an earlier-than-expected AAO of AD; parental history of early-onset dementia, APOE ε4 allele status, and hypertension were associated with a later-than-expected AAO of AD. Missense or frameshift variants within genes associated with AD pathogenesis were more common in participants with greater unexplained variability in intergenerational AAO of AD. Meaning Acquired and heritable factors were associated with a substantial proportion of variability in intergenerational AAO of AD.