Sun Sophie, Madge Victoria, Djordjevic Jelena, Gagnon Jean-François, Collins D Louis, Dagher Alain, Sharp Madeleine
Department of Neurology & Neurosurgery, McGill University, Montreal, Quebec, Canada.
Department of Biomedical Engineering, McGill University, Montreal, Quebec, Canada.
Mov Disord. 2025 May;40(5):844-854. doi: 10.1002/mds.30148. Epub 2025 Feb 13.
The substantia nigra (SN) and locus coeruleus (LC) are among the first brain regions to degenerate in Parkinson's disease (PD). This has important implications for early cognitive deficits because these nuclei are sources of ascending neuromodulators (i.e., dopamine and noradrenaline) that support various cognitive functions such as learning, memory, and executive function.
Our aim was to investigate the selective and independent contributions of SN and LC degeneration to cognitive deficits in PD.
We ran a cross-sectional study testing patients with PD and older adults on tasks of positive reinforcement learning, attention/working memory, executive function, and memory to measure cognitive performance in domains thought to be related to dopaminergic and noradrenergic function. Participants also underwent neuromelanin-sensitive magnetic resonance imaging as a measure of degeneration.
Reduced SN neuromelanin signal in PD was independently associated with impaired positive reinforcement learning (β = 0.41, 95% confidence interval [CI]: 0.08, 0.74) controlling for changes in the LC. In contrast, reduced LC neuromelanin signal was independently associated with impairments in attention/working memory (β = 0.20, 95% CI [-0.47, -0.10]) and executive function (β = 0.22, 95% CI: -0.57, -0.24), controlling for changes in the SN.
These results suggest that SN and LC degeneration may contribute to different cognitive deficits, potentially explaining the heterogeneity that exists in the cognitive manifestations of PD. These results also highlight the potential value of leveraging brain-behavior relationships to develop performance-based measures of cognition that could be used to characterize the phenotypic differences associated with underlying patterns of neurodegeneration. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
黑质（SN）和蓝斑（LC）是帕金森病（PD）中最早发生退化的脑区之一。这对早期认知缺陷具有重要意义，因为这些核团是支持学习、记忆和执行功能等各种认知功能的上行神经调质（即多巴胺和去甲肾上腺素）的来源。
我们的目的是研究SN和LC退化对PD认知缺陷的选择性和独立贡献。
我们进行了一项横断面研究，对PD患者和老年人进行正强化学习、注意力/工作记忆、执行功能和记忆任务测试，以测量与多巴胺能和去甲肾上腺素能功能相关领域的认知表现。参与者还接受了对神经黑色素敏感的磁共振成像检查，作为退化的一项指标。
在控制LC变化的情况下，PD患者SN神经黑色素信号降低与正强化学习受损独立相关（β = 0.41，95%置信区间[CI]：0.08，0.74）。相比之下，在控制SN变化的情况下，LC神经黑色素信号降低与注意力/工作记忆受损（β = 0.20，95% CI [-0.47, -0.10]）和执行功能受损（β = 0.22，95% CI：-0.57，-0.24）独立相关。
这些结果表明，SN和LC退化可能导致不同的认知缺陷，这可能解释了PD认知表现中存在的异质性。这些结果还强调了利用脑-行为关系来开发基于表现的认知测量方法的潜在价值，这些方法可用于表征与潜在神经退行性变模式相关的表型差异。© 2025作者。《运动障碍》由Wiley Periodicals LLC代表国际帕金森和运动障碍协会出版。
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