Orlando Isabella F, Shine James M, Robbins Trevor W, Rowe James B, O'Callaghan Claire
Brain and Mind Centre and School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Australia.
Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, CB2 3EB, United Kingdom.
Neurosci Biobehav Rev. 2023 Jun;149:105167. doi: 10.1016/j.neubiorev.2023.105167. Epub 2023 Apr 11.
Noradrenergic and cholinergic systems are among the most vulnerable brain systems in neuropsychiatric diseases of ageing, including Alzheimer's disease, Parkinson's disease, Lewy body dementia, and progressive supranuclear palsy. As these systems fail, they contribute directly to many of the characteristic cognitive and psychiatric symptoms. However, their contribution to symptoms is not sufficiently understood, and pharmacological interventions targeting noradrenergic and cholinergic systems have met with mixed success. Part of the challenge is the complex neurobiology of these systems, operating across multiple timescales, and with non-linear changes across the adult lifespan and disease course. We address these challenges in a detailed review of the noradrenergic and cholinergic systems, outlining their roles in cognition and behaviour, and how they influence neuropsychiatric symptoms in disease. By bridging across levels of analysis, we highlight opportunities for improving drug therapies and for pursuing personalised medicine strategies.
去甲肾上腺素能和胆碱能系统是衰老相关神经精神疾病中最易受损的脑系统之一，这些疾病包括阿尔茨海默病、帕金森病、路易体痴呆和进行性核上性麻痹。随着这些系统功能衰退，它们直接导致了许多典型的认知和精神症状。然而，人们对它们在症状产生中的作用了解尚不充分，针对去甲肾上腺素能和胆碱能系统的药物干预效果不一。部分挑战在于这些系统复杂的神经生物学特性，它们在多个时间尺度上发挥作用，并且在成年期寿命和疾病进程中呈现非线性变化。我们在对去甲肾上腺素能和胆碱能系统的详细综述中应对这些挑战，概述它们在认知和行为中的作用，以及它们如何在疾病中影响神经精神症状。通过跨越不同分析层面，我们强调了改善药物治疗和推行个性化医疗策略的机会。
