Modreanu Raluca, Cerquera Sonia Catalina, Martí María José, Ríos José, Sánchez-Gómez Almudena, Cámara Ana, Fernández Manel, Compta Yaroslau
Parkinson's Disease and Movement Disorders Unit, Neurology Service, ICN, Hospital Clínic, IDIBAPS, CIBERNED, University of Barcelona, Barcelona, Catalonia, Spain; Parkinson's Disease and Movement Disorders Unit, Neurology Service, Segeberger Kliniken, Bad Segeberg, Germany.
Parkinson's Disease and Movement Disorders Unit, Neurology Service, ICN, Hospital Clínic, IDIBAPS, CIBERNED, University of Barcelona, Barcelona, Catalonia, Spain; Neurology Unit, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Bogotá, Colombia.
J Neurol Sci. 2017 Feb 15;373:223-229. doi: 10.1016/j.jns.2016.12.064. Epub 2016 Dec 30.
Experimental, neuropathological and cerebrospinal fluid (CSF) studies support τ and amyloid-β (Aβ) relevance in Parkinson's disease (PD) related dementia. Lesser motor fluctuations (MFs) and non-motor features have also been related to PD-dementia. Yet, little is known about the association of MFs and non-motor symptoms with CSF τ and Aβ in PD. We hypothesized that lesser MFs and non-motor predominance are related to these CSF markers and dementia-risk in PD. We studied 58 PD patients (dementia at baseline, n=21; dementia at 18-months, n=35) in whom CSF Aβ and τ had been determined with ELISA techniques. MFs and a number of non-motor symptoms (apathy, anxiety, irritability, depression, visual hallucinations, spatial disorientation, memory complaints) over disease course were dichotomized as absent-mild vs. moderate-severe by retrospective clinical chart review blind to CSF findings. Non-motor predominance was defined as ≥3 non-motor symptoms (after the cohort-median of non-motor symptoms per patient) with ≥2 being moderate-severe and ≥1 having been present from onset, with all these being more disabling overall than motor features. Cross-sectionally, CSF biomarkers were non-parametrically compared according to dichotomized MFs and non-motor predominance. Longitudinally, dementia was the outcome (dependent variable), CSF markers, MFs and non-motor predominance were the predictors (independent variables), and potential modifiers as age, sex, and memory complaints were the covariates in binary regression models. Absent-mild MFs were associated with higher CSF τ markers and shorter time-to-dementia, while non-motor predominance and decreasing CSF Aβ independently increased longitudinal dementia-risk. In summary, absent-mild MFs, non-motor predominance and CSF τ and Aβ might define endophenotypes related to the timing or risk of dementia in PD.
实验性、神经病理学和脑脊液（CSF）研究支持τ和淀粉样β蛋白（Aβ）与帕金森病（PD）相关痴呆的相关性。较小的运动波动（MFs）和非运动特征也与PD痴呆有关。然而，关于PD中MFs和非运动症状与脑脊液τ和Aβ的关联知之甚少。我们假设较小的MFs和非运动优势与这些脑脊液标志物以及PD中的痴呆风险有关。我们研究了58例PD患者（基线时患有痴呆，n = 21；18个月时患有痴呆，n = 35），这些患者的脑脊液Aβ和τ已通过ELISA技术测定。通过对脑脊液结果不知情的回顾性临床图表审查，将疾病过程中的MFs和一些非运动症状（冷漠、焦虑、易怒、抑郁、视幻觉、空间定向障碍、记忆障碍）分为无-轻度与中度-重度。非运动优势定义为≥3种非运动症状（在每位患者非运动症状的队列中位数之后），其中≥2种为中度-重度，且≥1种自发病起就存在，所有这些症状总体上比运动特征更具致残性。横断面研究中，根据二分法的MFs和非运动优势对脑脊液生物标志物进行非参数比较。纵向研究中，痴呆是结果（因变量），脑脊液标志物、MFs和非运动优势是预测因素（自变量），年龄、性别和记忆障碍等潜在调节因素是二元回归模型中的协变量。无-轻度MFs与较高的脑脊液τ标志物和较短的痴呆发生时间相关，而非运动优势和脑脊液Aβ降低则独立增加纵向痴呆风险。总之，无-轻度MFs、非运动优势以及脑脊液τ和Aβ可能定义了与PD痴呆发生时间或风险相关的内表型。
