REVIEW article
Front. Endocrinol.
Sec. Neuroendocrine Science
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1655768
This article is part of the Research TopicAssociation of Diabetes Mellitus with Cognitive Impairment and Neurological Disorders Vol. 2View all 7 articles
Mechanisms Underlying Cognitive Impairment and Management Strategies in Type 2 Diabetes
Provisionally accepted
- Renmin Hospital of Wuhan University, Wuhan, China
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Type 2 diabetes (T2D) is increasingly recognized as a risk factor for cognitive impairment, ranging from mild cognitive impairment (MCI) to dementia. The underlying mechanisms involve a complex interplay of hyperglycemia, insulin resistance, neuroinflammation, oxidative stress, vascular dysfunction, and amyloid pathology. Effective management strategies remain an area of active investigation. This review explores the pathophysiological mechanisms linking T2D to cognitive dysfunction and evaluates current and emerging therapeutic strategies to preserve cognitive function in diabetic patients. Chronic hyperglycemia and insulin resistance impair neuronal function and synaptic plasticity, while microvascular complications contribute to cerebral hypoperfusion and white matter lesions. Additionally, metabolic disturbances exacerbate neurodegenerative processes, further compromising cognitive health. Effective management strategies for cognitive impairment in T2D include regular cognitive screening, stringent glycemic control, lifestyle modifications, comprehensive cardiovascular risk management, patient education and pharmacological interventions such as metformin, GLP-1 receptor agonists (GLP1RAs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors, which may offer neuroprotective benefits. In this review, we conclude that cognitive impairment in T2D results from complex, interrelated mechanisms requiring early intervention and personalized strategies. While current therapies focus on metabolic and vascular risk reduction, future research should prioritize biomarker discovery, mechanism-driven treatments, and long-term clinical trials to optimize outcomes. A proactive, integrated care model is essential to mitigate cognitive decline in this high-risk population.
Keywords: type 2 diabetes, cognitive impairment, Insulin Resistance, Neuroinflammation, glycemic control, Neuroprotection
Received: 28 Jun 2025; Accepted: 29 Sep 2025.
Copyright: © 2025 Chen, Huang and Xiong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaolin Chen, xiaolinchen@whu.edu.cn
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