Diabetes-Associated Cognitive Impairment: Pathophysiology and Emerging Therapies

Diabetes-associated cognitive impairment (DACI) is a common yet underrecognized condition, manifesting along a spectrum from mild cognitive impairment to dementia. DACI encompasses patients who develop vascular dementia (VaD) or Alzheimer's disease (AD) with diabetes as a risk factor; however, in certain patients, particularly those lacking clear VaD or AD features, diabetes may act as a primary driver of neurodegeneration. Mechanistically, DACI can be conceptualized as a neurovascular-metabolic disorder characterized by disruption of the neurovascular unit, impaired cerebral glucose metabolism, brain insulin resistance, and chronic neuroinflammation, contributing to small vessel disease, regional brain atrophy, and accelerated brain aging. In this narrative review, we synthesize current evidence on the clinical and imaging features of DACI, outline key mechanistic pathways linking diabetes to neurodegeneration, and discuss emerging therapeutic strategies, including GLP-1 receptor agonists and SGLT2 inhibitors, with potential neuroprotective effects. Greater recognition of DACI as a neurovascular-metabolic entity may facilitate earlier identification, inform biomarker development, and guide future trials aimed at preserving cognitive function in individuals with diabetes.