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Polygenic hazard scores in preclinical Alzheimer disease
Author(s) -
Tan Chin Hong,
Hyman Bradley T.,
Tan Jacinth J. X.,
Hess Christopher P.,
Dillon William P.,
Schellenberg Gerard D.,
Besser Lilah M.,
Kukull Walter A.,
Kauppi Karolina,
McEvoy Linda K.,
Andreassen Ole A.,
Dale Anders M.,
Fan Chun Chieh,
Desikan Rahul S.
Publication year - 2017
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25029
Subject(s) - asymptomatic , dementia , hazard ratio , medicine , apolipoprotein e , disease , alzheimer's disease , neuropathology , cognitive decline , incidence (geometry) , neurodegeneration , gerontology , confidence interval , physics , optics
Identifying asymptomatic older individuals at elevated risk for developing Alzheimer disease (AD) is of clinical importance. Among 1,081 asymptomatic older adults, a recently validated polygenic hazard score (PHS) significantly predicted time to AD dementia and steeper longitudinal cognitive decline, even after controlling for APOE ɛ4 carrier status. Older individuals in the highest PHS percentiles showed the highest AD incidence rates. PHS predicted longitudinal clinical decline among older individuals with moderate to high Consortium to Establish a Registry for Alzheimer's Disease (amyloid) and Braak (tau) scores at autopsy, even among APOE ɛ4 noncarriers. Beyond APOE , PHS may help identify asymptomatic individuals at highest risk for developing Alzheimer neurodegeneration. Ann Neurol 2017;82:484–488
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