Metabolic dysfunction and insulin resistance across major dementias: A comprehensive narrative review of the TyG index as a predictive marker.
Dementia is a progressive neurodegenerative disorder and a leading cause of disability worldwide, with Alzheimer's disease (AD), vascular dementia (VaD), and Lewy body dementias (LBD) representing the most common subtypes. Its rising prevalence, driven by population aging, underscores the urgent need for accessible biomarkers to support early risk identification and prevention. Insulin resistance (IR) has emerged as a key metabolic mechanism involved in cognitive decline and neurodegeneration. The triglyceride-glucose (TyG) index, derived from routine fasting glucose and triglyceride levels, is a simple and cost-effective surrogate marker of IR. Evidence suggests that higher TyG values are associated with an increased risk of dementia, adverse neuroimaging and biomarker profiles, and cerebrovascular and neurodegenerative changes, although findings remain heterogeneous. This review summarizes the current evidence linking the TyG index to major dementia subtypes and discusses the underlying pathophysiological mechanisms and clinical implications. A graphical abstract illustrating the proposed metabolic-neurodegenerative pathways is also provided.