Targeting Insulin Resistance to Treat Cognitive Dysfunction
- 23 January 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in Molecular Neurobiology
- Vol. 58 (6), 2672-2691
- https://doi.org/10.1007/s12035-021-02283-3
Abstract
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.Keywords
Funding Information
- Biomedical Laboratory Research and Development, VA Office of Research and Development (NEUD-004-07F)
This publication has 197 references indexed in Scilit:
- Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive ImpairmentArchives of Neurology, 2012
- Insulin biosynthesis in neuronal progenitors derived from adult hippocampus and the olfactory bulbEMBO Molecular Medicine, 2011
- Pioglitazone attenuates mitochondrial dysfunction, cognitive impairment, cortical tissue loss, and inflammation following traumatic brain injuryExperimental Neurology, 2011
- Rosiglitazone reversal of Tg2576 cognitive deficits is independent of peripheral gluco-regulatory statusBehavioural Brain Research, 2011
- Rosiglitazone Monotherapy in Mild-to-Moderate Alzheimer’s Disease: Results from a Randomized, Double-Blind, Placebo-Controlled Phase III StudyDementia and Geriatric Cognitive Disorders, 2010
- Rosiglitazone Rescues Memory Impairment in Alzheimer's Transgenic Mice: Mechanisms Involving a Reduced Amyloid and Tau PathologyNeuropsychopharmacology, 2010
- Diabetes-accelerated memory dysfunction via cerebrovascular inflammation and Aβ deposition in an Alzheimer mouse model with diabetesProceedings of the National Academy of Sciences of the United States of America, 2010
- Brain Glucose Overexposure and Lack of Acute Metabolic Flexibility in Obesity and Type 2 Diabetes: A PET-[18F]FDG Study in Zucker and ZDF RatsJournal of Cerebral Blood Flow & Metabolism, 2010
- Insulin-stimulated translocation of GLUT4 to the plasma membrane in rat hippocampus is PI3-kinase dependentBrain Research, 2009
- Overweight in midlife and risk of dementia: a 40-year follow-up studyInternational Journal of Obesity, 2009