Cognitive impairments in prediabetes and diabetes: From pathogenesis to comprehensive therapy
Abstract
Cognitive impairment, ranging from mild cognitive impairment to dementia, is increasingly recognized as a potential complication of diabetes. The rising prevalence of diabetes, coupled with an aging population, may lead to a significant increase in the prevalence of cognitive impairment among individuals with diabetes. The link between diabetes and cognitive impairment may reflect the direct effects of hyperglycemia on the brain or the impact of diabetes-related comorbidities, such as hypertension, dyslipidemia, or hyperinsulinemia. There is evidence of the influence of diabetic processes on both neurodegenerative and vascular processes, which contributes to both cognitive impairments similar to Alzheimer’s disease, such as amnestic impairments, and cerebrovascular cognitive impairments characterized by impaired executive cognitive functions. Hyperglycemia, obesity, and insulin resistance can cause microvascular dysfunction in the brain, which is already present in adults with prediabetes, leading to structural abnormalities in the brain such as vascularized lacunes, cerebral microhemorrhages, perivascular spaces, global brain atrophy, and microinfarcts, and there is increasing evidence that this is a key factor in cognitive decline. In addition, insulin or diabetes-related by-products may affect the amyloid cascade, which is thought to be responsible for Alzheimer’s disease. Therefore, the potential mechanisms linking diabetes to cognitive impairment are classified as cerebrovascular and non-cerebrovascular. Optimizing the treatment of cardiovascular risk factors in people with prediabetes and diabetes could be a potentially important therapeutic opportunity. Drugs with antioxidant and antihypoxic activity are promising in this regard. A literature search was conducted in the PubMed/MEDLINE, eLibrary, Cochrane Library, and Google Scholar electronic databases for the period from 1989 to 2025. A total of 216 literature sources were evaluated, of which 90 were included in the review.