Abstract
The relationship between the triglyceride glucose-body mass index (TyG-BMI) index and Alzheimer's disease (AD) pathology, cognition, and brain structure remains unclear. This study aimed to investigate these associations, focusing on cerebrospinal fluid (CSF) biomarkers, cognitive measures, and brain imaging data. Eight hundred and fifty-five non-demented participants were included. Linear regression was used to explore associations between the TyG-BMI index and AD pathology, cognition, and brain structure. The association between the TyG-BMI index and AD risk was assessed using Kaplan-Meier and Cox proportional hazards models. Longitudinal relationships were assessed using linear mixed-effects models. Mediation analyses were conducted to examine AD pathology's potential mediating role between the TyG-BMI index and cognition as well as brain structure. In the linear regression analyses, higher TyG-BMI levels were associated with increased Aβ(42) and decreased Tau, pTau, Tau/Aβ(42), pTau/Aβ(42), and pTau/Tau. Positive correlations were observed with mini-mental state examination (MMSE), memory (MEM), executive function (EF), and the volumes of the hippocampus, entorhinal cortex, and middle temporal regions, while negative correlations were found with Alzheimer's Disease Assessment Scale (ADAS). Longitudinally, the TyG-BMI index was inversely associated with ADAS, and positively with MMSE, MEM, EF, hippocampus, entorhinal, and middle temporal. High TyG-BMI levels were correlated with lower AD risk (HR 0.996 [0.994, 0.999]). Mediation analyses revealed AD pathology mediated the association between TyG-BMI index and cognition as well as brain structure. Additionally, the TyG-BMI index could mediate cognitive changes by influencing brain structure. The TyG-BMI index is associated with AD pathology, cognition, and brain structure.