Department of Psychology, University of California, Berkeley.
German Center for Neurodegenerative Diseases, Magdeburg, Germany.
JAMA Neurol. 2018 Feb 1;75(2):227-235. doi: 10.1001/jamaneurol.2017.3713.
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.
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.
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.
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).
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.
多种疾病过程与帕金森病（PD）患者的认知障碍有关，包括路易体、脑血管病和阿尔茨海默病。目前尚不清楚在没有痴呆的 PD 患者中，tau 病理学是否与认知有关。
比较认知正常的 PD 患者（PD-CN）、PD 伴轻度认知障碍（PD-MCI）患者和健康对照者的 tau 聚集情况，并评估 PD 患者中无痴呆患者的β-淀粉样蛋白（Aβ）、tau 和认知之间的关系。
设计、地点和参与者：这项横断面研究于 2015 年 7 月至 2016 年 10 月期间从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 和 15 名 PD-MCI）。1 名 PD-MCI 患者未接受磁共振成像扫描，因此未纳入所有分析；29 名 PD 患者被纳入本研究。参与者接受了氟 18 标记的 AV-1451 的 tau 正电子发射断层扫描（PET）、碳 11 标记的匹兹堡化合物 B 的 Aβ PET 扫描、磁共振成像、认知测试和神经评估。将影像学测量结果与 49 名健康对照者进行比较。
结局是 PD-CN 和 PD-MCI 患者组的 tau PET 测量值。我们假设各组的 tau 聚集与年龄和 Aβ 状态有关。
在 78 名参与者中，47 名（60%）为女性，平均（SD）年龄为 71.1（6.6）岁。6 名 PD 患者（21%）为 Aβ 阳性，其中 1 名轻度认知受损；23 名 Aβ 阴性（79%）。（49 名健康对照者中，25 名 Aβ 阴性，24 名 Aβ 阳性。）PD-CN 患者与 PD-MCI 患者之间以及所有 PD 患者与 Aβ 阴性对照者之间的全脑 tau PET 摄取的体素对比未显示出显著差异。PD-MCI 患者与 PD-CN 患者之间以及与 Aβ 阴性健康老年人之间，tau PET 结合在反映阿尔茨海默病 Braak 分期 1/2、3/4 或 5/6 的脑区没有差异。与 Aβ 阴性 PD 患者相比，Aβ 阳性 PD 患者在反映阿尔茨海默病 Braak 分期 3/4（1.22[0.07]与 1.14[0.07]；P=0.03）和 Braak 分期 5/6（1.20[0.07]与 1.11[0.08]；P=0.02）的脑区 tau PET 结合明显升高。
这些发现表明，在认知正常的 PD 患者、PD-MCI 患者和健康老年人中，皮质 Aβ 和 tau 的分布模式没有差异。年龄、Aβ 和 tau 不能区分 PD-CN 和 PD-MCI 患者。在 PD 患者和健康老年人中，tau 沉积与 Aβ 状态和年龄有关。在没有痴呆的 PD 患者中，认知障碍似乎与可测量的阿尔茨海默病无关。
