d'Angremont Emile, Renken Remco, van der Zee Sygrid, de Vries Erik F J, van Laar Teus, Sommer Iris E C
Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, Groningen, The Netherlands.
Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands.
Hum Brain Mapp. 2025 Feb 1;46(2):e70047. doi: 10.1002/hbm.70047.
Cognitive impairment is considered to be one of the key features of Parkinson's disease (PD), ultimately resulting in PD-related dementia in approximately 80% of patients over the course of the disease. Several distinct cognitive syndromes of PD have been suggested, driven by different neurotransmitter deficiencies and thus requiring different treatment regimes. In this study, we aimed to identify characteristic brain covariance patterns that reveal how cholinergic denervation is related to PD and to cognitive impairment, focusing on four domains, including attention, executive functioning, memory, and visuospatial cognition. We applied scaled sub-profile model principal component analysis to reveal cholinergic-specific disease-related and cognition-related covariance patterns using [F]fluoroethoxybenzovesamicol PET imaging. Stepwise logistic regression was applied to predict disease state (PD vs. healthy control). Linear regression models were applied to predict cognitive functioning within the PD group, for each cognitive domain separately. We assessed the performance of the identified patterns with leave-one-out cross validation and performed bootstrapping to assess pattern stability. We included 34 PD patients with various levels of cognitive dysfunction and 10 healthy controls, with similar age, sex, and educational level. The disease-related cholinergic pattern was strongly discriminative (AUC 0.91), and was most prominent in posterior brain regions, with lower tracer uptake in patients compared to controls. We found largely overlapping cholinergic-specific patterns across cognitive domains, with positive correlations between tracer uptake in the opercular cortex, left dorsolateral prefrontal cortex and posterior cingulate gyrus, among other regions, and attention, executive, and visuospatial functioning. Cross validation showed significant correlations between predicted and measured cognition scores, with the exception of memory. We identified a robust structural covariance pattern for the assessment of cholinergic dysfunction related to PD, as well as overlapping cholinergic patterns related to attentional, executive- and visuospatial impairment in PD patients.
认知障碍被认为是帕金森病（PD）的关键特征之一，在疾病过程中，最终约80%的患者会发展为与PD相关的痴呆。已有研究提出了几种不同的PD认知综合征，它们由不同的神经递质缺乏所驱动，因此需要不同的治疗方案。在本研究中，我们旨在识别特征性的脑协方差模式，以揭示胆碱能去神经支配与PD以及认知障碍之间的关系，重点关注四个领域，包括注意力、执行功能、记忆和视觉空间认知。我们应用缩放子剖面模型主成分分析，使用[F]氟乙氧基苯并维司那明PET成像来揭示胆碱能特异性疾病相关和认知相关的协方差模式。应用逐步逻辑回归来预测疾病状态（PD与健康对照）。分别对PD组内的每个认知领域应用线性回归模型来预测认知功能。我们通过留一法交叉验证评估所识别模式的性能，并进行自举法以评估模式稳定性。我们纳入了34名具有不同程度认知功能障碍的PD患者和10名健康对照，他们在年龄、性别和教育水平上相似。疾病相关的胆碱能模式具有很强的鉴别力（AUC为0.91），并且在脑后部区域最为突出，与对照组相比，患者的示踪剂摄取较低。我们发现在认知领域中胆碱能特异性模式在很大程度上重叠，在岛盖皮质、左侧背外侧前额叶皮质和后扣带回等区域的示踪剂摄取与注意力、执行功能和视觉空间功能之间呈正相关。交叉验证显示预测和测量的认知分数之间存在显著相关性，但记忆除外。我们确定了一种用于评估与PD相关的胆碱能功能障碍的稳健结构协方差模式，以及与PD患者注意力、执行功能和视觉空间损害相关的重叠胆碱能模式。
