Abstract Aims To investigate the association between metabolic obesity phenotypes and cognitive decline and evaluate the potential mediating role of C‐reactive protein (CRP). Methods Longitudinal cohort study using three waves (2008–2019) of the Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil). Data were analysed from December 2024 to May 2025. Baseline sample consisted of 15 105 participants aged 35–74 years. Six phenotypes were defined by body mass index (BMI) category (normal weight, overweight, obesity) and metabolic health. Metabolic health was defined using traditional metabolic syndrome criteria and more stringent criteria: low waist‐to‐hip ratio (WHR), no diabetes or hypertension. Global cognition Z‐scores were derived from tests of memory (immediate, delayed recall, and recognition of a word list), verbal fluency (phonemic and semantic), and Trail‐Making tests (TMT‐B). Mediation analysis evaluated CRP as a potential mediator. Results Among 12 795 participants (mean age 51.1 years; 55% women; 53% White) followed for a median of 8 years, metabolically unhealthy phenotypes—across all BMI categories—were associated with faster cognitive decline (β estimates ranged from −0.037 to −0.053; all p < 0.001), whereas metabolically healthy overweight (β = 0.016; 95% CI = −0.002, 0.034; p = 0.081) and metabolically healthy obesity (β = 0.000; 95% CI = −0.027, 0.026; p = 0.981) were not. No evidence of CRP mediation was identified. BMI was not associated with cognitive decline (β = −0.001; 95% CI = −0.002, 0.000; p = 0.170), whereas WHR was (β = −0.020, 95% CI = −0.026, −0.014, p < 0.001). Conclusions Metabolic dysfunction may be a stronger predictor of subsequent cognitive decline than excess body weight. Dementia prevention strategies may benefit from early identification and management of metabolic dysfunction across all weight categories.
Coelho et al. (Tue,) studied this question.
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