Considerable overlap has been identified in the risk factors, comorbidities and putative pathophysiological mechanisms of Alzheimer disease and related dementias (ADRDs) and type 2 diabetes mellitus (T2DM), two of the most pressing epidemics of our time. Much is known about the biology of each condition, but whether T2DM and ADRDs are parallel phenomena arising from coincidental roots in ageing or synergistic diseases linked by vicious pathophysiological cycles remains unclear. Insulin resistance is a core feature of T2DM and is emerging as a potentially important feature of ADRDs. Here, we review key observations and experimental data on insulin signalling in the brain, highlighting its actions in neurons and glia. In addition, we define the concept of 'brain insulin resistance' and review the growing, although still inconsistent, literature concerning cognitive impairment and neuropathological abnormalities in T2DM, obesity and insulin resistance. Lastly, we review evidence of intrinsic brain insulin resistance in ADRDs. By expanding our understanding of the overlapping mechanisms of these conditions, we hope to accelerate the rational development of preventive, disease-modifying and symptomatic treatments for cognitive dysfunction in T2DM and ADRDs alike.

阿尔茨海默氏病和相关痴呆（ADRDs）和2型糖尿病（T2DM）的风险因素，合并症和假定的病理生理机制存在相当大的重叠，这是当今最紧迫的两种流行病。关于每种病状的生物学知之甚少，但是尚不清楚T2DM和ADRD是衰老的巧合根源还是由恶性病理生理周期导致的协同疾病引起的平行现象。胰岛素抵抗是T2DM的核心特征，并且正在成为ADRD的潜在重要特征。在这里，我们回顾了关于大脑中胰岛素信号传导的主要观察结果和实验数据，重点介绍了其在神经元和神经胶质细胞中的作用。此外，我们定义了“脑胰岛素抵抗”的概念并回顾了其增长的趋势，尽管仍然不一致，有关T2DM的认知障碍和神经病理学异常，肥胖症和胰岛素抵抗的文献。最后，我们回顾了ADRD中内在的脑胰岛素抵抗的证据。通过扩大我们对这些情况的重叠机制的理解，我们希望加速对T2DM和ADRD中认知功能障碍的预防，疾病缓解和对症治疗的合理发展。