Association of Early- to Midlife Weight Trajectories With Mid- to Late-Life Cognitive Decline in the ELSA-Brasil Study

While midlife obesity is consistently associated with cognitive decline in later life, there is limited understanding of how weight variations from early life to midlife affect cognitive decline. We investigated the association between early- to midlife weight trajectories and mid- to late-life cognitive decline. This is a longitudinal cohort study that used data from 3 waves (2008-2019) of the Brazilian Longitudinal Study of Adult Health, a multicenter cohort study that enrolled active and retired public servants aged 35+ years from public universities in Brazil. Participants with a history of stroke, missing cognitive data at baseline, and with incomplete body shape data were excluded from the analyses. Self-reported body shapes from ages 5 to 40 using the Stunkard Figure Rating Scale were categorized as underweight, normal, overweight, and obese. Sequence analysis and hierarchical clustering identified weight trajectories. Global cognition Z-scores were derived from memory (immediate recall, delayed recall, and recognition of a word list), phonemic and semantic verbal fluency, and Trail Making Test part B (TMT-B). Linear mixed models adjusted for sociodemographic, clinical, and lifestyle covariates investigated associations between clusters of weight trajectories and global cognition Z-scores. Inverse probability of attrition weighting was used to account for attrition bias. Among 11,361 participants (mean age: 51.5 ± 8.6, 55% women, 42.4% Black/mixed race), "normal to overweight," "underweight to normal," and "stable overweight" trajectories exhibited faster global cognitive decline than "stable normal" trajectory (β = -0.024; 95% CI -0.043 to -0.005; p = 0.015; β = -0.026; 95% CI -0.040 to -0.012; p < 0.001; β = -0.034; 95% CI -0.066 to -0.001; p = 0.043, respectively), representing 4.6-6.5 excess years of cognitive aging over a median follow-up of 8 years. Cognitive decline associated with weight trajectories was driven mainly by declines in memory and TMT-B performance. Associations were observed only in Black/mixed races and women when stratified. Weight gain and stable overweight trajectories from early life to midlife were associated with faster cognitive decline than stable normal weight trajectories. Weight management during early life may mitigate cognitive decline. Study limitations include reliance on self-reported body shape data, potential recall bias, and residual confounding from unmeasured early-life factors.