Brain energy failure in dementia syndromes: Opportunities and challenges for glucagon‐like peptide‐1 receptor agonists
Open Access
- 14 October 2021
- journal article
- review article
- Published by Wiley in Alzheimer's & Dementia
- Vol. 18 (3), 478-497
- https://doi.org/10.1002/alz.12474
Abstract
Medications for type 2 diabetes (T2DM) offer a promising path for discovery and development of effective interventions for dementia syndromes. A common feature of dementia syndromes is an energy failure due to reduced energy supply to neurons and is associated with synaptic loss and results in cognitive decline and behavioral changes. Among diabetes medications, glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) promote protective effects on vascular, microglial, and neuronal functions. In this review, we present evidence from animal models, imaging studies, and clinical trials that support developing GLP-1 RAs for dementia syndromes. The review examines how changes in brain energy metabolism differ in conditions of insulin resistance and T2DM from dementia and underscores the challenges that arise from the heterogeneity of dementia syndromes. The development of GLP-1 RAs as dementia therapies requires a deeper understanding of the regional changes in brain energy homeostasis guided by novel imaging biomarkers.Funding Information
- National Institute on Aging (R01AG055770, R01AG054434, R01AG067063)
- Alzheimer's Association (NIRG‐15‐361854)
- National Institutes of Health (P50AG05142)
This publication has 182 references indexed in Scilit:
- Exenatide promotes cognitive enhancement and positive brain metabolic changes in PS1-KI mice but has no effects in 3xTg-AD animalsCell Death & Disease, 2013
- Multifunctional role of astrocytes as gatekeepers of neuronal energy supplyFrontiers in Cellular Neuroscience, 2013
- Analysis of metabolism of 6FDG: a PET glucose transport tracerNuclear Medicine and Biology, 2011
- Insulin Resistance and Alzheimer-like Reductions in Regional Cerebral Glucose Metabolism for Cognitively Normal Adults With Prediabetes or Early Type 2 DiabetesArchives of Neurology, 2011
- Glial and neuronal control of brain blood flowNature, 2010
- Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistanceNeurobiology of Learning and Memory, 2010
- Memory impairment, executive dysfunction, and intellectual decline in preclinical Alzheimer's diseaseJournal of the International Neuropsychological Society, 2008
- Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer diseaseFEBS Letters, 2008
- Alzheimer's Disease and Mild Cognitive ImpairmentNeurologic Clinics, 2007
- Supply and Demand in Cerebral Energy Metabolism: The Role of Nutrient TransportersJournal of Cerebral Blood Flow & Metabolism, 2007