The triglyceride-glucose (TyG) index is derived from a combination of fasting plasma glucose and triglyceride levels, making it a reliable indicator of insulin resistance. Prior studies have established a significant connection between insulin resistance and Alzheimer's disease (AD). Nevertheless, the relationship between the trajectory of the TyG index and AD onset is still not clearly understood.This longitudinal prospective cohort study derived data from the Framingham Heart Study Offspring cohort. A total of 2170 participants without AD at baseline were included and were prospectively followed until 2018. Groups of participants with comparable TyG index trajectories were identified through the application of latent class growth mixture modeling analysis.A cohort of 163 participants were diagnosed with AD during the follow-up. The incidence of AD in the low, moderate, and high trajectory groups was 0.38, 0.66, and 0.68 per 100 person-years respectively. Compared to the low trajectory group, both the moderate trajectory (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.04-2.25) and high trajectory groups (HR = 1.90, 95%CI: 1.09-3.31) exhibited an elevated risk of developing AD. These results remained consistent after adjusting for multiple covariates (moderate: HR = 1.53, 95%CI: 1.02-2.29; high: HR = 1.84, 95%CI: 1.03-3.27, respectively).Higher TyG index trajectories exhibit a notable correlation with the development of AD. Early and continuous monitoring of the TyG index in individuals identified as high-risk for AD may help implement timely prevention measures.Copyright © 2025. Published by Elsevier España, S.L.U.