Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, United Kingdom.
Brain and Mind Centre and School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
Mov Disord. 2022 Aug;37(8):1663-1672. doi: 10.1002/mds.29072. Epub 2022 May 16.
Neurodegeneration in the locus coeruleus (LC) contributes to neuropsychiatric symptoms in both Parkinson's disease (PD) and progressive supranuclear palsy (PSP). Spatial precision of LC imaging is improved with ultrahigh field 7 T magnetic resonance imaging.
This study aimed to characterize the spatial patterns of LC pathological change in PD and PSP and the transdiagnostic relationship between LC signals and neuropsychiatric symptoms.
Twenty-five people with idiopathic PD, 14 people with probable PSP-Richardson's syndrome, and 24 age-matched healthy controls were recruited. Participants underwent clinical assessments and high-resolution (0.08 mm ) 7 T-magnetization-transfer imaging to measure LC integrity in vivo. Spatial patterns of LC change were obtained using subregional mean contrast ratios and significant LC clusters; we further correlated the LC contrast with measures of apathy and cognition, using both mixed-effect models and voxelwise analyses.
PSP and PD groups showed significant LC degeneration in the caudal subregion relative to controls. Mixed-effect models revealed a significant interaction between disease-group and apathy-related correlations with LC degeneration (β = 0.46, SE [standard error] = 0.17, F(1, 35) = 7.46, P = 0.01), driven by a strong correlation in PSP (β = -0.58, SE = 0.21, t(35) = -2.76, P = 0.009). Across both disease groups, voxelwise analyses indicated that lower LC integrity was associated with worse cognition and higher apathy scores.
The relationship between LC and nonmotor symptoms highlights a role for noradrenergic dysfunction across both PD and PSP, confirming the potential for noradrenergic therapeutic strategies to address transdiagnostic cognitive and behavioral features in neurodegenerative disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
蓝斑核（LC）的神经退行性变导致帕金森病（PD）和进行性核上性麻痹（PSP）的神经精神症状。超高场 7T 磁共振成像提高了 LC 成像的空间精度。
本研究旨在描述 PD 和 PSP 中 LC 病理变化的空间模式，以及 LC 信号与神经精神症状之间的跨诊断关系。
招募了 25 名特发性 PD 患者、14 名可能的 PSP-Richardson 综合征患者和 24 名年龄匹配的健康对照者。参与者接受了临床评估和高分辨率（0.08mm）7T 磁化传递成像，以测量体内 LC 的完整性。使用亚区平均对比比和显著的 LC 簇获得 LC 变化的空间模式；我们进一步使用混合效应模型和体素分析，将 LC 对比与淡漠和认知测量相关联。
PSP 和 PD 组与对照组相比，LC 尾侧亚区明显退化。混合效应模型显示，疾病组与淡漠相关的 LC 退化之间存在显著的相互作用（β=0.46，SE[标准误差]=0.17，F（1，35）=7.46，P=0.01），这是由 PSP 中强烈的相关性驱动的（β=-0.58，SE=0.21，t（35）=-2.76，P=0.009）。在两组疾病中，体素分析表明，LC 完整性越低，认知越差，淡漠评分越高。
LC 与非运动症状之间的关系突出了去甲肾上腺素能功能障碍在 PD 和 PSP 中的作用，证实了去甲肾上腺素能治疗策略有可能解决神经退行性疾病中的跨诊断认知和行为特征。
