<h4>Objective</h4>The purpose of this study is to investigate whether depression may mediate the association between arthritis and mild cognitive impairment (MCI) in diverse BMI-based obese populations with multi-parameter metabolic signatures including insulin resistance, inflammatory markers, and lipid metabolism indices.<h4>Methods</h4>The relationships between arthritis, MCI, and depression were investigated in a large-scale study that used logistic regression, subgroup analyses, and mediation analyses. The gene discussed is INS; the disease is arthritic joint disease.