Rocky Mountain Regional VA Medical Center, Aurora, CO, USA.
Department of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA.
Mol Neurobiol. 2021 Jun;58(6):2672-2691. doi: 10.1007/s12035-021-02283-3. Epub 2021 Jan 23.
Dementia is a devastating disease associated with aging. Alzheimer's disease is the most common form of dementia, followed by vascular dementia. In addition to clinically diagnosed dementia, cognitive dysfunction has been reported in diabetic patients. Recent studies are now beginning to recognize type 2 diabetes mellitus, characterized by chronic hyperglycemia and insulin resistance, as a risk factor for Alzheimer's disease and other cognitive disorders. While studies on insulin action have remained traditionally in the domain of peripheral tissues, the detrimental effects of insulin resistance in the central nervous system on cognitive dysfunction are increasingly being reported by recent clinical and preclinical studies. The findings from these studies suggest that antidiabetic drugs have the potential to be used to treat dementia. In this review, we discuss the physiological functions of insulin in the brain, studies on the evaluation of cognitive function under conditions of insulin resistance, and reports on the beneficial actions of antidiabetic drugs in the brain. This review covers clinical studies as well as investigations in animal models and will further highlight the emerging link between insulin resistance and neurodegenerative disorders.
痴呆症是一种与衰老相关的破坏性疾病。阿尔茨海默病是最常见的痴呆症形式，其次是血管性痴呆症。除了临床诊断的痴呆症外，糖尿病患者也有认知功能障碍的报道。最近的研究现在开始将 2 型糖尿病（以慢性高血糖和胰岛素抵抗为特征）视为阿尔茨海默病和其他认知障碍的危险因素。虽然胰岛素作用的研究仍然传统上局限于外周组织，但最近的临床和临床前研究越来越多地报告了中枢神经系统中胰岛素抵抗对认知功能障碍的有害影响。这些研究的结果表明，抗糖尿病药物有可能用于治疗痴呆症。在这篇综述中，我们讨论了胰岛素在大脑中的生理功能、胰岛素抵抗条件下评估认知功能的研究，以及抗糖尿病药物在大脑中的有益作用的报告。本综述涵盖了临床研究以及动物模型的研究，并将进一步强调胰岛素抵抗与神经退行性疾病之间的新联系。
