Triglyceride-glucose index is associated with cerebral small vessel disease-related motor impairment in Parkinson's disease: a mediation analysis.

BACKGROUND: Cerebral small vessel disease (CSVD) may worsen motor and cognitive impairment in Parkinson's disease (PD), yet whether peripheral metabolic inflammation mediates this link remains unclear. The triglyceride-glucose (TyG) index, a surrogate for insulin resistance, has been associated with CSVD and neurodegeneration. This study examined whether the TyG index statistically accounts for the association between CSVD burden and motor or cognitive deficits in PD. METHODS: This retrospective cross-sectional study enrolled 362 PD patients. The 4-point scale assessed CSVD burden. Movement Disorder Society Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) and Montreal Cognitive Assessment (MoCA) evaluated motor and cognitive function, separately. Spearman correlation and mediation analyses were performed, adjusting for age, sex, education, hypertension, diabetes, and daily dose equivalent of levodopa. Sensitivity analyses were conducted to assess the robustness and specificity of the findings. RESULTS: CSVD burden was positively associated with MDS-UPDRS III (total effect = 2.309, 95% CI [0.463, 4.155, p = 0.014]) and negatively associated with TyG index (a = -0.067, p = 0.025). TyG index was negatively associated with MDS-UPDRS III (b = -6.561, p < 0.001). The indirect effect was 0.441 (95% CI [0.048, 0.958]), accounting for 19.1% of the total effect. This mediation was specific to TyG, as four alternative inflammatory indices showed no significant effects. Additional analyses adjusting for disease duration and Hoehn-Yahr staging confirmed robustness [indirect effect = 0.288, 95% CI (0.019, 0.687)]. Neither fasting triglycerides nor glucose alone mediated the effect. No mediation was found for cognition. CONCLUSION: The TyG index statistically accounts for part of the association between CSVD and motor function in PD via a negative-to-negative pathway, suggesting a hypothesis-generating metabolic target that warrants prospective investigation.