Ignatavicius Anna, Matar Elie, Lewis Simon J G
Faculty of Medicine and Health, Central Clinical School, University of Sydney, Sydney, NSW 2050, Australia.
Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, Sydney, NSW 2113, Australia.
Brain. 2025 Feb 3;148(2):376-393. doi: 10.1093/brain/awae289.
Visual hallucinations are a common non-motor feature of Parkinson's disease and have been associated with accelerated cognitive decline, increased mortality and early institutionalization. Despite their prevalence and negative impact on patient outcomes, the repertoire of treatments aimed at addressing this troubling symptom is limited. Over the past two decades, significant contributions have been made in uncovering the pathological and functional mechanisms of visual hallucinations, bringing us closer to the development of a comprehensive neurobiological framework. Convergent evidence now suggests that degeneration within the central cholinergic system may play a significant role in the genesis and progression of visual hallucinations. Here, we outline how cholinergic dysfunction may serve as a potential unifying neurobiological substrate underlying the multifactorial and dynamic nature of visual hallucinations. Drawing upon previous theoretical models, we explore the impact that alterations in cholinergic neurotransmission has on the core cognitive processes pertinent to abnormal perceptual experiences. We conclude by highlighting that a deeper understanding of cholinergic neurobiology and individual pathophysiology may help to improve established and emerging treatment strategies for the management of visual hallucinations and psychotic symptoms in Parkinson's disease.
视幻觉是帕金森病常见的非运动症状,与认知功能加速衰退、死亡率增加及过早入住护理机构有关。尽管视幻觉普遍存在且对患者预后有负面影响,但针对这一棘手症状的治疗方法却很有限。在过去二十年里,人们在揭示视幻觉的病理和功能机制方面取得了重大进展,使我们更接近建立一个全面的神经生物学框架。目前越来越多的证据表明,中枢胆碱能系统的退化可能在视幻觉的发生和发展中起重要作用。在此,我们概述胆碱能功能障碍如何可能作为视幻觉多因素和动态性质潜在的统一神经生物学基础。借鉴以往的理论模型,我们探讨胆碱能神经传递改变对与异常感知体验相关的核心认知过程的影响。最后我们强调,深入了解胆碱能神经生物学和个体病理生理学可能有助于改进现有的和新出现的治疗策略,以管理帕金森病中的视幻觉和精神症状。