Metabolic dysfunction and cognitive impairment in patients with depression: The role of the TyG index and peripheral...

Cognitive impairment is frequent in major depressive disorder (MDD), yet its link to metabolic dysfunction and inflammation remains unclear.

In this cross-sectional study (February 2023-September 2024), 210 patients with MDD and 120 healthy controls (HCs) were assessed. Clinical and biochemical measures included fasting plasma glucose (FPG), triglycerides (TG), and the triglyceride-glucose index (TyG index). Cognitive performance was evaluated using the montreal cognitive assessment (MoCA), depression severity with the 17-item 1amilton depression rating scale (HAMD-17), and inflammation via interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP). Associations were analyzed through correlation, multiple regression, mediation, and receiver operating characteristic (ROC) analyses, with subgroup tests by sex, disease duration, and medication status.

Compared with controls, MDD patients had higher BMI, FPG, TG, TyG index, and inflammatory markers, and lower MoCA scores (all P < 0.001). TyG index was negatively correlated with MoCA total score (r = -0.496, P < 0.001), notably in delayed recall, attention, and visuospatial/executive domains. IL-6, TNF-α, and CRP were also inversely related to MoCA (r = -0.376 to -0.402, P < 0.001). Mediation analysis showed that IL-6 and TNF-α partly mediated the TyG-MoCA association (joint indirect effect 30.98 % of total; total indirect 37.17 %, 95 % CI excluding zero). The combined TyG + IL-6 + TNF-α model yielded better discrimination for cognitive impairment (AUC = 0.792 vs 0.674, P < 0.001).

Elevated TyG index is associated with poorer cognition in MDD, partly through inflammatory pathways, suggesting a metabolic-inflammatory mechanism underlying depression-related cognitive decline.