Comprehensive Risk Factors for Alzheimer's Disease and Cognitive Function Before Middle Age in the U.S.

ImportanceAlzheimers disease (AD) is a major health concern in the U.S., but most research has focused on older populations. Few studies investigate AD risk factors and cognitive function in young to early midlife adults. ObjectiveTo examine whether key AD risk factors are associated with cognition before midlife. Design, Setting, ParticipantsData from the National Longitudinal Study of Adolescent to Adult Health (Add Health) were analyzed. Participants were enrolled in 1994-95 (grades 7-12) and followed through 2018. We analyzed survey and biomarker data from Waves IV (median age 28) and V (median age 38). ExposuresCardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score, APOE {varepsilon}4 status, Amyloid Tau and Neurodegeneration markers (ATN), including total Tau and Neurofilament light (NfL), high sensitivity C-reactive protein (hsCRP), Interleukin (IL)-1{beta}, IL-6, IL-8, IL-10, and Tumor necrosis factor alpha (TNF-). Main OutcomesImmediate word recall, delayed word recall, and backward digit span. ResultsWe analyzed data separately in Wave IV (ranging from N=4,507 to N=11,449) and Wave V (ranging from N=529 to N=1,121). Approximately half were female. The CAIDE score was associated with all cognition measures in Wave IV. For example, among adults aged 24-34, each 1-point increase in CAIDE was associated with a 0.03 SD lower backward digit span score (95% CI: -0.04, -0.02). No significant associations were found between APOE {varepsilon}4 and cognition. Total Tau was associated with immediate word recall in Wave V ({beta}=-0.14, 95% CI: -0.24, -0.04). Wave IV hsCRP and IL-10 and Wave V IL-6, IL-1{beta} and IL-8 were also associated with lower cognitive scores. ConclusionsKey risk factors for AD, including cardiovascular, ATN, and immune markers, are linked to cognitive function as early as ages 24-44, highlighting the need for early prevention in the US.