ε4 and Accelerated Cognitive Decline Among Cognitively Healthy Middle-Aged and Older Adults

Is ε4 carrier status associated with accelerated cognitive decline in cognitively healthy adults in Taiwan, and does an -excluded polygenic risk score estimate risk of similar decline?In this cohort study of 4392 adults aged 55 years and older, ε4 carriers—especially homozygotes—showed accelerated decline in Mini-Mental State Examination scores, diverging from noncarriers after age 70 years. The polygenic risk score was not associated with cognitive decline during the 6-year mean follow-up period.In this study, ε4 carrier status was associated with early cognitive decline, highlighting midlife risk awareness and lifestyle interventions, while non- polygenic risk may require longer follow-up to manifest.

Corresponding Author: Wei J. Chen, MD, ScD, Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli 35053, Taiwan (wjchen@nhri.edu.tw).

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