4.6 Review

Targeting Insulin Resistance to Treat Cognitive Dysfunction

Journal

MOLECULAR NEUROBIOLOGY
Volume 58, Issue 6, Pages 2672-2691

Publisher

SPRINGER
DOI: 10.1007/s12035-021-02283-3

Keywords

Insulin resistance; Metabolic syndrome; Obesity; Diabetes; Dementia; Alzheimer's disease

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Funding

  1. Veterans Administration [NEUD-004-07F]

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Dementia, particularly Alzheimer's disease and vascular dementia, is strongly associated with aging. Recent studies have highlighted the potential link between type 2 diabetes mellitus, cognitive dysfunction, and the development of Alzheimer's disease and other cognitive disorders. Research is increasingly focusing on the physiological functions of insulin in the brain, the evaluation of cognitive function under conditions of insulin resistance, and the potential use of antidiabetic drugs to treat dementia.
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.

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