Preservation of brain health is a worldwide priority. The traditional view is that the major threats to the ageing brain lie within the brain itself. Consequently, therapeutic approaches have focused on protecting the brain from these presumably intrinsic pathogenic processes. However, an increasing body of evidence has unveiled a previously under-recognized contribution of peripheral organs to brain dysfunction and damage. Thus, in addition to the well-known impact of diseases of the heart and endocrine glands on the brain, accumulating data suggest that dysfunction of other organs, such as gut, liver, kidney and lung, substantially affects the development and clinical manifestation of age-related brain pathologies. In this Review, a framework is provided to indicate how organ dysfunction can alter brain homeostasis and promote neurodegeneration, with a focus on dementia. We delineate the associations of subclinical dysfunction in specific organs with dementia risk and provide suggestions for public health promotion and clinical management.

保护大脑健康是全世界的首要任务。传统观点认为，衰老大脑的主要威胁在于大脑本身。因此，治疗方法的重点是保护大脑免受这些可能的内在致病过程的影响。然而，越来越多的证据揭示了外周器官对脑功能障碍和损伤的先前未被充分认识的贡献。因此，除了众所周知的心脏和内分泌腺疾病对大脑的影响外，越来越多的数据表明，其他器官（如肠道、肝脏、肾脏和肺）的功能障碍会严重影响与年龄相关的脑部病变的发展和临床表现。在本综述中，提供了一个框架来说明器官功能障碍如何改变大脑稳态并促进神经退化，重点是痴呆。我们描述了特定器官亚临床功能障碍与痴呆风险的关联，并为公共卫生促进和临床管理提供了建议。