# Association of metabolic obesity phenotypes with cognitive decline in the ELSA‐Brasil study

## TL;DR

The study finds that poor metabolic health, regardless of weight, is linked to faster cognitive decline, suggesting that metabolic dysfunction may be more important than body weight in predicting cognitive issues.

## Contribution

This study identifies that metabolically unhealthy individuals, regardless of BMI, experience faster cognitive decline compared to metabolically healthy individuals.

## Key findings

- Metabolically unhealthy phenotypes were associated with faster cognitive decline across all BMI categories.
- Metabolically healthy overweight and obesity were not associated with cognitive decline.
- C-reactive protein (CRP) did not mediate the association between metabolic phenotypes and cognitive decline.

## Abstract

To investigate the association between metabolic obesity phenotypes and cognitive decline and evaluate the potential mediating role of C‐reactive protein (CRP).

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.

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).

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.