Most U.S. Alzheimer’s disease (AD) research focuses on older adults, leaving little understanding of risk factors earlier in life across representative populations. Using nationally representative data from Waves IV and V of the National Longitudinal Study of Adolescent to Adult Health (Add Health), researchers investigated whether widely cited AD risk factors and blood biomarkers are associated with cognitive function before midlife. Risk factors were assessed using the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) Score, a comprehensive algorithm integrating social, behavioral, and biological factors such as education, sex, age, cholesterol, blood pressure, body mass index, and physical activity. Biomarkers included APOE ε4 status, two neuropathological ATN markers (total Tau and neurofilament light chain [NfL]), and several inflammatory molecules and interleukins, including high-sensitivity C-reactive protein (hsCRP), IL-1β, IL-6, IL-8, IL-10, and TNF-α. Cognitive function was assessed using three tests: immediate word recall, delayed word recall and backward digit span.
The study included 4,507–11,449 participants in Wave IV (median age 28) and 529–1,121 in Wave V (median age 38). Roughly half were women, and most were White, with smaller proportions of Black and Hispanic participants. Findings showed that higher CAIDE scores were linked to lower performance on all three cognitive tests in Wave IV. In Wave V, higher levels of total Tau were linked to worse immediate word recall results. In both Wave IV and V, blood markers of inflammation (such as hsCRP, IL-6, IL-1β, IL-8, and IL-10) were also linked to lower cognitive scores across all tests. This study shows that known Alzheimer’s risk factors are linked to cognitive function in adults aged 24–44, not just older populations, emphasizing that prevention efforts in the U.S. should begin earlier.
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Risk factors for Alzheimer’s disease and cognitive function before middle age in a U.S. representative population-based study. Aiello, Allison E. et al.The Lancet Regional Health – Americas, Volume 45, 101087