Associations of Anthropometry Measures Across 35 Years With Late-Life Plasma P-tau217 and Dementia

BACKGROUND AND OBJECTIVES: Central and general adiposity have been linked to dementia risk, but their relation to blood-based Alzheimer disease (AD) biomarkers is unclear. We examined life course adiposity, measured by waist-to-height ratio (WtHR) and body mass index (BMI), in relation to plasma p-tau217 and to AD dementia verified by biomarker status. METHODS: ε4, lifestyle, and mental health. RESULTS: The final study sample comprised 8,797 participants (53.5% women, mean age at HUNT4 77.8 [SD 6.2]). Of these, 2,649 (30.1%) were p-tau217-positive and 659 (7%) had biomarker-verified AD dementia. Midlife WtHR ≥0.60 was associated with 12.8% (95% CI 7.3-19.7) higher late-life p-tau217 concentration and higher risk of positive p-tau217 (relative risk ratios [RRRs] 1.55, 1.21-1.99) and biomarker-verified AD dementia (RRR 1.84, 1.27-2.65) compared with WtHR <0.50. In late life, WtHR ≥0.60 was associated with 15.6% (-19.0 to -12.2) lower p-tau217 concentration and lower risk of positive p-tau217 (RRR 0.49, 0.41-0.59) and biomarker-verified AD dementia (RRR 0.63, 0.46-0.86). BMI showed similar patterns: Midlife obesity was associated with higher p-tau217 concentration and elevated risk of biomarker-verified AD dementia, whereas late-life overweight/obesity was associated with lower p-tau217 and decreased risk of biomarker-verified AD dementia. Among those with positive p-tau217 or biomarker-verified AD dementia, mixed-effects regression showed higher midlife adiposity, reversing by late life. DISCUSSION: Our results identify midlife central and general adiposity as modifiable risk factors for AD pathology and AD dementia. WtHR may aid early risk stratification and inform interventions targeting central fat reduction.