Parkinson Disease and Movement Disorders Unit, Neurology Service, IDIBAPS, CIBERNED, Hospital Clínic, Barcelona, Catalonia, Spain.
Parkinsonism Relat Disord. 2013 Aug;19(8):717-24. doi: 10.1016/j.parkreldis.2013.03.009. Epub 2013 May 3.
Neuropsychological (mostly posterior-cortical) deficits, quantitative magnetic resonance imaging (MRI) atrophy patterns, and low cerebrospinal fluid (CSF) levels of amyloid-β have been separately related to worsening cognition in Parkinson's disease (PD). However, these biomarkers have not been longitudinally assessed in combination as PD-dementia predictors. In this prospective longitudinal study, 27 non-demented PD patients underwent CSF, neuropsychological and 3-T brain-MRI studies at baseline and were re-assessed 18 months later in terms of progression to dementia (primary outcome) and longitudinal neuropsychological and cortical thickness changes (secondary outcomes). At follow-up 11 patients (41%) had progressed to dementia. Lower CSF amyloid-β, worse verbal learning, semantic fluency and visuoperceptual scores, and thinner superior-frontal/anterior cingulate and precentral regions were significant baseline dementia predictors in binary logistic regressions as quantitative and/or dichotomised traits. All participants without baseline biomarker abnormalities remained non-demented whereas all with abnormalities in each biomarker type progressed to dementia, with intermediate risk for those showing abnormalities in a single to two biomarker types (p = 0.006). Both the dementia-outcome and low baseline CSF amyloid-β were prospectively associated with limbic and posterior-cortical neuropsychological decline and frontal, limbic and posterior-cortical thinning from baseline to follow-up. These findings suggest that the combination of CSF amyloid-β, neuropsychological and cortical thickness biomarkers might provide a basis for dementia-risk stratification and progression monitoring in PD.
神经心理学（主要是皮质后部）缺陷、定量磁共振成像（MRI）萎缩模式以及脑脊液（CSF）中β-淀粉样蛋白水平降低已分别与帕金森病（PD）认知能力恶化有关。然而，这些生物标志物尚未作为 PD 痴呆的预测因子进行纵向评估。在这项前瞻性纵向研究中，27 名非痴呆 PD 患者在基线时接受了 CSF、神经心理学和 3-T 脑 MRI 研究，并在 18 个月后根据向痴呆的进展（主要结果）和纵向神经心理学和皮质厚度变化（次要结果）进行重新评估。在随访时，11 名患者（41%）进展为痴呆。较低的 CSF 淀粉样蛋白-β、较差的言语学习、语义流畅性和视知觉评分以及较薄的额上/前扣带和中央前区在二项逻辑回归中是基线痴呆的显著预测因子，这些预测因子是定量的和/或二分类的特征。所有无基线生物标志物异常的参与者仍保持非痴呆状态，而所有具有单一至两种生物标志物类型异常的患者均进展为痴呆，具有单一至两种生物标志物类型异常的患者风险中等（p=0.006）。痴呆结局和基线 CSF 淀粉样蛋白-β均与从基线到随访的边缘和皮质后部神经心理学下降以及额、边缘和皮质后部变薄呈前瞻性相关。这些发现表明，CSF 淀粉样蛋白-β、神经心理学和皮质厚度生物标志物的组合可能为 PD 中的痴呆风险分层和进展监测提供依据。
