Type 2 diabetes and cognitive impairment: From pathogenesis to preventive therapy and future strategies

Type 2 diabetes mellitus (T2DM) and cognitive impairment (CI), including dementia, are global medico-social problems that are pathogenetically closely linked and form a vicious cycle. Despite an understanding of the shared mechanisms, the traditional approach focused solely on glycemic control proves insufficient for preventing cognitive decline.

The aim: to summarize current insights into the pathogenetic relationship between T2DM and CI and to substantiate the need for a shift towards a new paradigm of preventive, pathogenetically targeted therapy aimed at preserving cognitive health.

Material and methods. An analysis of modern epidemiological, observational, and randomized clinical trials, as well as systematic reviews and meta-analyses, dedicated to studying the relationship between T2DM, cardiometabolic risk factors, and CI, and assessing the potential neuroprotective properties of specific classes of glucose-lowering drugs was conducted.

Results. The key role of comprehensive management of cardiometabolic risk factors (blood pressure control, dyslipidemia, insulin resistance) and subclinical atherosclerosis (carotid intima-media thickness) in CI prevention is demonstrated. The promise of using drugs with pleiotropic activity, such as pioglitazone (thiazolidinedione) and alogliptin (DPP-4 inhibitor), which target common pathogenetic links of T2DM and neurodegeneration (cerebral insulin resistance, neuroinflammation, atherosclerosis), is substantiated. Evidence of their ability to reduce the risk of dementia, recurrent stroke, and atherosclerosis progression is presented. Particular attention is paid to the benefits of early combination therapy, specifically the fixed-dose combination of alogliptin and pioglitazone, which provides powerful glycemic control with a minimal risk of hypoglycemia and a comprehensive impact on multiple defects of T2DM.

Conclusion. The implementation of an integrative, preventive strategy, including aggressive control of cardiometabolic risk factors, early screening for CI, and targeted prescription of pathogenetically justified glucose-lowering therapy with neuroprotective potential, is a necessary condition for reducing the risk of cognitive impairment and dementia in patients with T2DM.

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