Dementia is a potentially avertable tragedy, currently considered among the top 10 greatest global health challenges of the twenty-first century. Dementia not only robs individuals of their dignity and independence, it also has a ripple effect that starts with the inflicted individual’s family and projects to the society as a whole. The constantly growing number of cases, along with the lack of effective treatments and socioeconomic impact, poses a serious threat to the sustainability of our health care system. Hence, there is a worldwide effort to identify new targets for the treatment of Alzheimer’s disease (AD), the leading cause of dementia. Due to its multifactorial etiology and the recent clinical failure of several novel amyloid-β (Aβ) targeting therapies, a comprehensive “multitarget” approach may be most appropriate for managing this condition. Interestingly, renin angiotensin system (RAS) modulators were shown to positively impact all the factors involved in the pathophysiology of dementia including vascular dysfunction, Aβ accumulation, and associated cholinergic deficiency, in addition to tau hyperphosphorylation and insulin derangements. Furthermore, for many of these drugs, the preclinical evidence is also supported by epidemiological data and/or preliminary clinical trials. The purpose of this review is to provide a comprehensive update on the major causes of dementia including the risk factors, current diagnostic criteria, pathophysiology, and contemporary treatment strategies. Moreover, we highlight the angiotensin II receptor type 2 (AT2R) as an effective drug target and present ample evidence supporting its potential role and clinical applications in cognitive impairment to encourage further investigation in the clinical setting.

痴呆症是一种可以避免的悲剧，目前被认为是二十一世纪全球十大健康挑战之一。痴呆症不仅剥夺个人的尊严和独立性，还会产生连锁反应，从患者的家庭开始，波及整个社会。病例数量不断增加，加上缺乏有效的治疗方法和社会经济影响，对我们医疗保健系统的可持续性构成严重威胁。因此，全世界都在努力寻找治疗阿尔茨海默病（AD）的新靶标，阿尔茨海默病是痴呆的主要原因。由于其病因学多因素以及最近几种新型淀粉样蛋白-β (Aβ) 靶向疗法的临床失败，综合的“多靶点”方法可能最适合治疗这种疾病。有趣的是，除了 tau 蛋白过度磷酸化和胰岛素紊乱之外，肾素血管紧张素系统 (RAS) 调节剂还可以对参与痴呆病理生理学的所有因素产生积极影响，包括血管功能障碍、Aβ 积累和相关的胆碱能缺乏。此外，对于许多此类药物，临床前证据也得到流行病学数据和/或初步临床试验的支持。本综述的目的是提供有关痴呆症主要原因的全面更新，包括危险因素、当前诊断标准、病理生理学和当代治疗策略。此外，我们强调 2 型血管紧张素 II 受体 (AT2R) 作为有效的药物靶点，并提供充足的证据支持其在认知障碍中的潜在作用和临床应用，以鼓励在临床环境中进行进一步研究。