Mediation analysis evaluated CRP as a potential mediator.<h4>Results</h4>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. This evidence concerns the gene CRP and obesity disorder.