Department of Medicine, University of Southern California, Keck School of Medicine USC, Los Angeles, California, USA.
Department of Neurology, University of Southern California, Keck School of Medicine USC, Los Angeles, California, USA.
Alzheimers Dement. 2022 Mar;18(3):478-497. doi: 10.1002/alz.12474. Epub 2021 Oct 14.
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.
用于 2 型糖尿病（T2DM）的药物为发现和开发痴呆综合征的有效干预措施提供了有希望的途径。痴呆综合征的一个共同特征是由于神经元的能量供应减少而导致的能量衰竭，这与突触损失有关，并导致认知能力下降和行为改变。在糖尿病药物中，胰高血糖素样肽-1（GLP-1）受体激动剂（RAs）对血管、小胶质细胞和神经元功能具有保护作用。在这篇综述中，我们提供了来自动物模型、影像学研究和临床试验的证据，支持开发用于痴呆综合征的 GLP-1 RAs。该综述检查了在胰岛素抵抗和 T2DM 与痴呆的情况下，大脑能量代谢的变化有何不同，并强调了由于痴呆综合征的异质性而带来的挑战。GLP-1 RAs 作为痴呆症治疗药物的开发需要更深入地了解由新型成像生物标志物指导的大脑能量平衡的区域变化。
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