Pathogenetic aspects of dementia in patients with type 2 diabetes mellitus

This review presents data from current Russian and international scientific studies on the causes and pathogenetic mechanisms of dementia in patients with type 2 diabetes mellitus (T2DM). Currently, T2DM is regarded as an independent risk factor for cognitive impairment and various dementia types, including vascular, mixed, and Alzheimer disease-related dementia. Dementia is a polyetiologic syndrome, and Alzheimer’s disease and cerebrovascular pathology are considered the predominant causes in the elderly. Several studies reported an association between diabetes mellitus and neurodegenerative processes in the central nervous system. Cognitive impairments caused by suboptimal neurogenesis, brain tissue insulin resistance, dysglycemia, oxidative stress, chronic systemic inflammation, β-amyloid peptide accumulation, and structural and functional changes in the cerebral vasculature are prevalent in the elderly, who are more frequently diagnosed with both dementia and T2DM. Key contributors to dementia include genetic predisposition, environmental factors, lifestyle, and diet. However, growing evidence indicates additional risk factors such as insulin resistance, hypertension, obesity, dyslipidemia, amylin metabolism disorders, and gut microbiota imbalance. Brain tissue insulin resistance, often called “type 3 diabetes mellitus” and closely associated with cognitive impairment, is particularly significant. Moreover, poor glycemic control and recurrent hypoglycemic episodes play a role in cognitive deficits in patients with diabetes mellitus. Nevertheless, the molecular and cellular mechanisms underlying dementia in T2DM remain unclear.