Protecting the Aging Brain in Diabetes: Mechanism, Biomarkers, and Emerging Therapeutic Frontiers in Cognitive...

Diabetes, which impacts over 500 million individuals globally, has been identified as a significant risk factor for accelerated cognitive aging, mild cognitive impairment, and various forms of dementia, including Alzheimer's disease and vascular dementia. Despite its clinical relevance, cognitive decline remains an underrecognized complication within diabetes management. This comprehensive review aims to synthesize evidence across the mechanisms, biomarkers, and therapeutic approaches pertinent to diabetes-associated cognitive impairment, with a particular emphasis on the aging brain. The primary literature search was conducted across the decade 2015-2025; however, earlier landmark studies and foundational scientific contributions have been selectively included where necessary to contextualize contemporary findings within the broader historical trajectory of the field. A systematic literature search was executed across PubMed, MEDLINE, Embase, and PsycINFO utilizing MeSH terms such as "type 2 diabetes mellitus," "cognitive decline," "dementia," "insulin resistance," "neuroinflammation," and "neuroprotection." Diabetes contributes to accelerated brain aging via several convergent pathways, including insulin resistance, chronic neuroinflammation, oxidative stress, blood-brain barrier dysfunction, and cerebrovascular damage. These mechanisms facilitate amyloid-beta accumulation and tau hyperphosphorylation, thereby linking diabetes to the Alzheimer's disease spectrum. Promising biomarkers for early detection include plasma p-tau 217, neurofilament light chain, and various neuroimaging markers.