帕金森病患者Tau、β-淀粉样蛋白与认知的关系。

PubMed ID
发表日期 2018年02月

原始出处 JAMA神经病学
JAMA neurology
作者 Winer  Joseph R  Maass  Anne  Pressman  Peter  Stiver  Jordan  Schonhaut  Daniel R  Baker  Suzanne L  Kramer  Joel  Rabinovici  Gil D  Jagust  William J 

文献标题 帕金森病患者Tau、β-淀粉样蛋白与认知的关系。
Associations Between Tau, β-Amyloid, and Cognition in Parkinson Disease.

文献摘要 Importance

多种疾病过程与帕金森病(PD)的认知障碍有关,包括路易体病、脑血管病和阿尔茨海默病。目前尚不清楚tau病理学是否与无痴呆的PD患者的认知有关。

Objective

比较认知正常的PD患者(PD-CN)、轻度认知障碍的PD患者(PD-MCI)和健康对照组参与者的tau聚集情况,并评估未患痴呆的PD患者的β-淀粉样蛋白(Aβ)、tau和认知之间的关系。

Design, Setting, and Participants

这项横断面研究从2015年7月至2016年10月从一家三级医疗中心和研究机构招募了30名帕金森病患者(15名PD-CN患者和15名PD-MCI患者)。一名PD-MCI患者未接受磁共振成像扫描,因此被排除在所有分析之外;本研究包括29例PD患者。参与者接受氟18标记AV-1451的tau正电子发射断层扫描(PET),碳11标记匹兹堡化合物B的AβPET扫描,磁共振成像,认知测试和神经评估。影像测量与49名健康对照参与者进行比较。

Main Outcomes and Measures

结果是PD-CN和PD-MCI患者组的tau-PET测量。我们假设各组间的tau聚集与年龄和Aβ状态有关。

Results

在78名参与者中,47名(60%)为女性,平均年龄(SD)为71.1(6.6)岁。6例PD患者(21%)Aβ阳性,其中1例轻度认知功能障碍;23例Aβ阴性(79%)。(在49名健康对照中,25名为Aβ阴性,24名为Aβ阳性。)PD-CN患者和PD-MCI患者之间以及所有PD患者和Aβ阴性对照组之间全脑tau-PET摄取的体素对比未显示出显著差异。在反映阿尔茨海默病Braak 1/2、3/4或5/6期的脑区,PD-MCI和PD-CN患者的Tau-PET结合没有差异,并且与Aβ阴性的健康老年人没有差异。在反映阿尔茨海默病Braak 3/4期的脑区内,与Aβ阴性PD患者相比,Aβ阳性PD患者的平均(SD)tau-PET结合显著升高(1.22[0.07]vs 1.14[0.07];P = .03)和Braak阶段5/6(1.20[0.07]vs 1.11[0.08];P = .02).

Conclusions and Relevance

这些发现表明,PD-CN患者、PD-MCI患者和健康老年人的皮质Aβ和τ的模式没有差异。年龄、Aβ和tau不能区分PD-CN和PD-MCI患者。在帕金森病患者和健康老年人中,Tau沉积与Aβ状态和年龄有关。无痴呆的帕金森病患者的认知缺陷似乎并不反映可测量的阿尔茨海默病。


Importance

Multiple disease processes are associated with cognitive impairment in Parkinson disease (PD), including Lewy bodies, cerebrovascular disease, and Alzheimer disease. It remains unknown whether tau pathology relates to cognition in patients with PD without dementia.

Objective

To compare tau aggregation in patients with PD who are cognitively normal (PD-CN), patients with PD with mild cognitive impairment (PD-MCI), and healthy control participants, and evaluate the relationships between β-amyloid (Aβ), tau, and cognition in patients with PD who did not have dementia.

Design, Setting, and Participants

This cross-sectional study recruited 30 patients with Parkinson disease (15 with PD-CN and 15 with PD-MCI) from a tertiary care medical center and research institutions from July 2015 through October 2016. One patient with PD-MCI did not receive a magnetic resonance imaging scan and thus was excluded from all analyses; 29 patients with PD were included in the present study. Participants underwent tau positron emission tomographic (PET) scanning with fluorine 18-labeled AV-1451, Aβ PET scanning with carbon 11-labeled Pittsburgh compound B, magnetic resonance imaging, cognitive testing, and neurologic evaluation. Imaging measures were compared with 49 healthy control participants.

Main Outcomes and Measures

Outcomes were tau PET measurements of groups of patients with PD-CN and PD-MCI. We hypothesized that tau aggregation across groups would be related to age and Aβ status.

Results

Of the 78 participants, 47 (60%) were female, and the mean (SD) age was 71.1 (6.6) years. Six patients with PD (21%) were Aβ-positive, of whom 1 was mildly cognitively impaired; 23 were Aβ-negative (79%). (Of the 49 healthy controls, 25 were Aβ-negative and 24 Aβ-positive.) Voxelwise contrasts of whole-brain tau PET uptake between patients with PD-CN and patients with PD-MCI, and additionally between all patients with PD and Aβ-negative controls, did not reveal significant differences. Tau PET binding did not differ between patients with PD-MCI and PD-CN in brain regions reflecting Alzheimer disease Braak stages 1/2, 3/4, or 5/6, and did not differ from Aβ-negative healthy older adults. Mean (SD) tau PET binding was significantly elevated in Aβ-positive patients with PD relative to Aβ-negative patients with PD within brain regions reflecting Alzheimer disease Braak stage 3/4 (1.22 [0.07] vs 1.14 [0.07]; P = .03) and Braak stage 5/6 (1.20 [0.07] vs 1.11 [0.08]; P = .02).

Conclusions and Relevance

These findings suggest that patterns of cortical Aβ and tau do not differ in people with PD-CN, people with PD-MCI, and healthy older adults. Age, Aβ, and tau do not differentiate patients with PD-CN and PD-MCI. Tau deposition is related to Aβ status and age in both people with PD and healthy older adults. Cognitive deficits in people with PD without dementia do not appear to reflect measureable Alzheimer disease.


获取全文 10.1001/jamaneurol.2017.3713