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前驱期路易体痴呆神经精神症状背后的脑网络连通性

Brain network connectivity underlying neuropsychiatric symptoms in prodromal Lewy body dementia.

作者信息

Wright Laura M, Donaghy Paul C, Burn David J, Taylor John-Paul, O'Brien John T, Yarnall Alison J, Matthews Fiona E, Firbank Michael J, Sigurdsson Hilmar P, Schumacher Julia, Thomas Alan J, Lawson Rachael A

机构信息

Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK; NIHR Newcastle Biomedical Research Centre, UK.

Department of Psychiatry, University of Cambridge, Cambridge, UK.

出版信息

Neurobiol Aging. 2025 Jul;151:95-106. doi: 10.1016/j.neurobiolaging.2025.04.007. Epub 2025 Apr 17.

Abstract

Neuropsychiatric symptoms (NPS) are prevalent, emerge early, and are associated with poorer outcomes in Lewy body dementia (LBD). Research suggests NPS may reflect LBD-related dysfunction in distributed neuronal networks. This study investigated NPS neural correlates in prodromal LBD using resting-state functional MRI. Fifty-seven participants were included with mild cognitive impairment (MCI) with Lewy bodies (MCI-LB, n = 28) or Parkinson's disease (PD-MCI, n = 29). Functional MRI assessed connectivity within five resting-state networks: primary visual, dorsal attention, salience, limbic, and default mode networks. NPS were measured using the Neuropsychiatric Inventory. Principal component analyses identified three neuropsychiatric factors: affective disorder (apathy, depression), psychosis (delusions, hallucinations) and anxiety. Seed-to-voxel connectivity maps were analysed to determine associations between NPS and network connectivity. In PD-MCI, affective symptoms and anxiety were associated with greater connectivity between limbic orbitofrontal cortex and default mode areas, including medial prefrontal cortex, subgenual cingulate and precuneus, and weaker connectivity between limbic orbitofrontal cortex and the brainstem and between the salience network and medial prefrontal cortex (all pFWE<0.001). Psychosis severity in PD-MCI correlated with connectivity across multiple networks (all pFWE<0.001). In MCI-LB, no significant correlations were found between NPS severity and network connectivity. However, participants with anxiety demonstrated a trend towards greater connectivity within medial prefrontal areas than those without (pFWE=0.046). Altered connectivity within and between networks associated with mood disorders may explain affective and anxiety symptoms in PD-MCI. Neural correlates of NPS in MCI-LB, however, remain unclear, highlighting the need for research in larger, more diverse LBD populations to identify symptomatic treatment targets.

摘要

神经精神症状(NPS)在路易体痴呆(LBD)中普遍存在、出现较早,且与较差的预后相关。研究表明,NPS可能反映了分布式神经元网络中与LBD相关的功能障碍。本研究使用静息态功能磁共振成像(fMRI)调查前驱期LBD中NPS的神经相关性。纳入了57名患有路易体轻度认知障碍(MCI-LB,n = 28)或帕金森病(PD-MCI,n = 29)的参与者。功能磁共振成像评估了五个静息态网络内的连通性:初级视觉网络(primary visual)、背侧注意网络(dorsal attention)、突显网络(salience)、边缘系统网络(limbic)和默认模式网络(default mode)。使用神经精神科问卷(Neuropsychiatric Inventory)测量NPS。主成分分析确定了三个神经精神因素:情感障碍(冷漠、抑郁)、精神病(妄想、幻觉)和焦虑。分析种子点到体素的连通性图,以确定NPS与网络连通性之间的关联。在PD-MCI中,情感症状和焦虑与边缘眶额皮质与默认模式区域(包括内侧前额叶皮质、膝下扣带回和楔前叶)之间更强的连通性相关,而边缘眶额皮质与脑干之间以及突显网络与内侧前额叶皮质之间的连通性较弱(所有pFWE<0.001)。PD-MCI中的精神病严重程度与多个网络的连通性相关(所有pFWE<0.001)。在MCI-LB中,未发现NPS严重程度与网络连通性之间存在显著相关性。然而,有焦虑症状的参与者比没有焦虑症状的参与者在内侧前额叶区域内表现出更强连通性的趋势(pFWE = 0.046)。与情绪障碍相关的网络内部和之间的连通性改变可能解释了PD-MCI中的情感和焦虑症状。然而,MCI-LB中NPS的神经相关性仍不清楚,这突出表明需要对更大、更多样化的LBD人群进行研究,以确定对症治疗靶点。

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