Cognitive Performance in Early Neuronal Synuclein Disease with Hyposmia but without Motor Disability: Association with Dopamine Deficiency and Isolated Rapid Eye Movement Sleep Behavior Disorder.

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2025-07-11 DOI:10.1002/ana.27263

Daniel Weintraub, Anuprita R Nair, Ryan Kurth, Michael C Brumm, Christine Kohnen, Michele K York, Roseanne D Dobkin, Kenneth Marek, Caroline Tanner, Tanya Simuni, Andrew Siderowf, Douglas Galasko, Lana M Chahine, Christopher Coffey, Kalpana Merchant, Kathleen L Poston, Tatiana Foroud, Brit Mollenhauer, Ethan G Brown, Karl Kieburtz, Mark Frasier, Sohini Chowdhury, Roy N Alcalay, Aleksandar Videnovic

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引用次数: 0

Abstract

Objective: To determine the impact of dopamine deficiency and isolated rapid eye movement (REM) sleep behavior disorder (iRBD) on cognitive performance in early neuronal α-synuclein disease (NSD) with hyposmia but without motor disability.

Methods: Using Parkinson's Progression Markers Initiative baseline data, cognitive performance was assessed with a cognitive summary score (CSS) derived from robust healthy control (HC) norms. Performance was examined for participants with hyposmia in early NSD-Integrated Staging System (NSD-ISS), either stage 2A (cerebrospinal fluid α-synuclein seed amplification assay [SAA]+, dopamine transporter scan [DaTscan]-) or 2B (SAA+, DaTscan+).

Results: Participants were stage 2A (n = 101), stage 2B (N = 227), and HCs (n = 158). Although stage 2 had intact Montreal Cognitive Assessment scores (mean [SD] = 27.0 [2.3]), stage 2A had a numerically worse CSS (z-score mean difference = 0.05, p = NS; effect size = 0.09) and stage 2B a statistically worse CSS (z-score mean difference = 0.23, p < 0.05; effect size = 0.40) compared with HCs. In stage 2A, hyposmia alone was associated with normal cognition, but those with comorbid iRBD had significantly worse cognition (z-score mean difference = 0.33, p < 0.05, effect size =0.50). In stage 2B, hyposmia alone had abnormal cognition (z-score mean difference = 0.18, p = 0.0078, effect size = 0.29), and superimposed iRBD had a statistically significant additive effect.

Interpretation: Using a novel CSS, we demonstrated that hyposmia is associated with cognitive deficits in prodromal NSD without motor disability, particularly when comorbid dopamine system impairment or comorbid iRBD is present. Therefore, it is critical to include and assess cognition at all stages when studying synuclein disease, even in the absence of motor disability. ANN NEUROL 2025.

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早期神经元突触核蛋白疾病伴低血症但无运动障碍的认知表现：与多巴胺缺乏和孤立的快速眼动睡眠行为障碍有关

目的：探讨多巴胺缺乏和孤立性快速眼动（REM）睡眠行为障碍（iRBD）对早期伴有低氧但无运动障碍的神经元性α-突触核蛋白病（NSD）认知表现的影响。方法：使用帕金森病进展标志物倡议基线数据，使用来自稳健健康对照（HC）规范的认知总结评分（CSS）评估认知表现。在早期nsd综合分期系统（NSD-ISS）中检测低血症患者的表现，包括2A期（脑脊液α-突触核蛋白种子扩增试验[SAA]+，多巴胺转运体扫描[DaTscan]-）或2B期（SAA+, DaTscan+）。结果：参与者为2A期（n = 101）、2B期（n = 227）和hc期（n = 158）。尽管第2阶段的蒙特利尔认知评估评分完好无损（平均[SD] = 27.0[2.3]），但第2A阶段的CSS数值更差(z-score平均差异= 0.05,p = NS；解释：使用一种新的CSS，我们证明了低体温与无运动障碍的前驱NSD的认知缺陷有关，特别是当共病多巴胺系统损伤或共病iRBD存在时。因此，在研究突触核蛋白疾病时，包括和评估所有阶段的认知是至关重要的，即使在没有运动障碍的情况下。Ann neurol 2025。

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

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.