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.

中文翻译：

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痴呆综合征中的脑能量衰竭：胰高血糖素样肽 1 受体激动剂的机遇和挑战

2 型糖尿病 (T2DM) 药物为发现和开发痴呆综合征的有效干预措施提供了一条有希望的途径。痴呆综合征的一个共同特征是由于对神经元的能量供应减少而导致的能量衰竭，并且与突触丧失有关，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 (RA) 可促进对血管、小胶质细胞和神经元功能的保护作用。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，这些证据支持开发用于痴呆综合征的 GLP-1 RA。该综述研究了脑能量代谢的变化在胰岛素抵抗和痴呆引起的 T2DM 的情况下有何不同，并强调了痴呆综合征的异质性带来的挑战。