Cholinergic dysfunction in isolated rapid eye movement sleep behaviour disorder links to impending phenoconversion

IF 4.5 2区医学 Q1 CLINICAL NEUROLOGY

European Journal of Neurology Pub Date : 2024-10-03 DOI:10.1111/ene.16503

Miriam H. Terkelsen, Alex Iranzo, Mónica Serradell, Andreas M. Baun, Morten G. Stokholm, Erik Hvid Danielsen, Karen Østergaard, Marit Otto, Kristina B. Svendsen, Mette Møller, Erik L. Johnsen, Alicia Garrido, Dolores Vilas, Joan Santamaria, Arne Møller, Carles Gaig, David J. Brooks, Per Borghammer, Eduardo Tolosa, Nicola Pavese

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Abstract

Background and purpose

Most patients with isolated rapid eye movement sleep behaviour disorder (iRBD) progress to a parkinsonian alpha-synucleinopathy. However, time to phenoconversion shows great variation. The aim of this study was to investigate whether cholinergic and dopaminergic dysfunction in iRBD patients was associated with impending phenoconversion.

Methods

Twenty-one polysomnography-confirmed iRBD patients underwent baseline ¹¹C-donepezil and 6-Fluoro-(¹⁸F)-l-3,4-dihydroxyphenylalanine (¹⁸F-DOPA) positron emission tomography (PET). Potential phenoconversion was monitored for up to 8 years. PET images were analysed according to patients' diagnoses after 3 and 8 years using linear regression. Time-to-event analysis was made with Cox regression, dividing patients into low and high tracer uptake groups.

Results

Follow-up was accomplished in 17 patients. Eight patients progressed to either Parkinson's disease (n = 4) or dementia with Lewy bodies (n = 4), while nine remained non-phenoconverters. Compared with non-phenoconverters, 8-year phenoconverters had lower mean ¹¹C-donepezil uptake in the parietal (p = 0.032) and frontal cortex (p = 0.042), whereas mean ¹¹C-donepezil uptake in 3-year phenoconverters was lower in the parietal cortex (p = 0.005), frontal cortex (p = 0.025), thalamus (p = 0.043) and putamen (p = 0.049). Phenoconverters within 3 years and 8 years had lower ¹⁸F-DOPA uptake in the putamen (p < 0.001). iRBD patients with low parietal ¹¹C-donepezil uptake had a 13.46 (95% confidence interval 1.42;127.21) times higher rate of phenoconversion compared with those with higher uptake (p = 0.023). iRBD patients with low ¹⁸F-DOPA uptake in the most affected putamen were all phenoconverters with higher rate of phenoconversion (p = 0.0002).

Conclusions

These findings suggest that cortical cholinergic dysfunction, particularly within the parietal cortex, could be a biomarker candidate for predicting short-term phenoconversion in iRBD patients. This study aligns with previous reports suggesting dopaminergic dysfunction is associated with forthcoming phenoconversion.

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孤立性快速眼动睡眠行为障碍中的胆碱能功能障碍与即将出现的表型转换有关。

背景和目的：大多数孤立性眼球快速运动睡眠行为障碍（iRBD）患者都会发展为帕金森α-突触核蛋白病。然而，表型转换的时间差异很大。本研究旨在探讨iRBD患者的胆碱能和多巴胺能功能障碍是否与即将发生的表型转换有关：21名经多导睡眠图证实的iRBD患者接受了基线11C-多奈哌齐和6-氟-(18F)-l-3,4-二羟基苯丙氨酸（18F-DOPA）正电子发射断层扫描（PET）。对潜在的表型转换进行了长达 8 年的监测。根据患者 3 年和 8 年后的诊断结果，采用线性回归法分析 PET 图像。采用 Cox 回归法进行时间到事件分析，将患者分为低示踪剂摄取组和高示踪剂摄取组：结果：对 17 名患者进行了随访。八名患者进展为帕金森病（4 人）或路易体痴呆（4 人），九名患者仍为非苯丙酮转换者。与非表观改变者相比，8 年表观改变者顶叶皮层（p = 0.032）和额叶皮层（p = 0.042）的平均 11C 多奈哌齐摄取量较低，而 3 年表观改变者顶叶皮层（p = 0.005）、额叶皮层（p = 0.025）、丘脑（p = 0.043）和普鲁士门（p = 0.049）的平均 11C 多奈哌齐摄取量较低。与摄取量较高者相比，3年内和8年内的表型转换者在普鲁士脑中的18F-DOPA摄取量较低（p 11C-多奈哌齐摄取量较高者的表型转换率为13.46（95%置信区间为1.42;127.21）倍（p = 0.023）。iRBD患者在受影响最严重的普鲁士脑中的18F-DOPA摄取量较低，表型转换率较高（p = 0.0002）：这些研究结果表明，皮质胆碱能功能障碍，尤其是顶叶皮质内的胆碱能功能障碍，可能是预测 iRBD 患者短期表型转换的候选生物标志物。这项研究与之前的报告一致，即多巴胺能功能障碍与即将出现的表型转换有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Neurology 医学-临床神经学

CiteScore

9.70

自引率

2.00%

发文量

418

审稿时长

1 months

期刊介绍： The European Journal of Neurology is the official journal of the European Academy of Neurology and covers all areas of clinical and basic research in neurology, including pre-clinical research of immediate translational value for new potential treatments. Emphasis is placed on major diseases of large clinical and socio-economic importance (dementia, stroke, epilepsy, headache, multiple sclerosis, movement disorders, and infectious diseases).