18F-Flortaucipir PET 与阿尔茨海默病导致的轻度认知障碍患者的脑脊液、认知和神经影像学的相关性。

18F-Flortaucipir PET Associations with Cerebrospinal Fluid, Cognition, and Neuroimaging in Mild Cognitive Impairment due to Alzheimer's Disease.

机构信息

Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.

Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA, USA.

出版信息

J Alzheimers Dis. 2020;74(2):589-601. doi: 10.3233/JAD-191330.

DOI:10.3233/JAD-191330

PMID:32065800

Abstract

BACKGROUND

Tau positron emission tomography (PET) imaging is used in research, but its relation to cerebrospinal fluid (CSF) tau and other Alzheimer's disease (AD)-related clinical measures is unclear in mild cognitive impairment with AD biomarkers (MCI-AD).

OBJECTIVE

To determine associations between 18F-flortaucipir PET and CSF AD biomarkers, cognitive functioning, and neuroimaging measures in MCI-AD.

METHODS

In 29 participants 50 years or older with MCI-AD, 18F-flortaucipir PET, CSF total tau (T-tau), phosphorylated tau181p (P-tau), amyloid-β (Aβ), structural MRI, and neuropsychological testing were collected as baseline assessments of an ongoing clinical trial. 11C-Pittsburgh compound B PET was simultaneously conducted in 20 participants. Associations between 18F-flortaucipir PET and these measures were assessed by multiple linear regression adjusted for potential confounders and using global, lobar, and voxel-wise standardized uptake value ratio (SUVr).

RESULTS

Whole brain 18F-flortaucipir SUVr was significantly associated with CSF T-tau (r = 0.68, p < 0.001) and P-tau (r = 0.42, p = 0.04) after adjusting for age, sex, race, and education, with strongest associations in the temporal region (T-tau: r = 0.69, p < 0.001; P-tau: r = 0.49, p = 0.02). Voxel-wise analysis confirmed these regional associations. 18F-flortaucipir PET was also associated with CSF Aβ (r = -0.45, p = 0.03), episodic memory (r = -0.61, p = 0.001), visuospatial working memory (r = -0.46, p = 0.02), and brain cortical thickness (r = -0.44, p = 0.03) but not hippocampal volume. In the amyloid PET subset, although 11C-PiB PET associated strongly with 18F-flortaucipir (r = 0.79, p≤0.001), associations were stronger between 11C-PiB and key outcomes, compared to 18F-flortaucipir.

CONCLUSION

18F-flortaucipir PET is moderately associated with CSF AD biomarkers and other AD-related phenotypes. The associations in this MCI-AD sample are stronger than previously described in other populations.

摘要

背景

tau 正电子发射断层扫描（PET）成像用于研究，但在具有 AD 生物标志物的轻度认知障碍（MCI-AD）中，其与脑脊液（CSF）tau 和其他 AD 相关临床指标的关系尚不清楚。

目的

确定 18F-flortaucipir PET 与 MCI-AD 中 CSF AD 生物标志物、认知功能和神经影像学测量之间的关联。

方法

在 29 名年龄在 50 岁或以上的 MCI-AD 参与者中，在一项正在进行的临床试验的基线评估中，收集了 18F-flortaucipir PET、CSF 总 tau（T-tau）、磷酸化 tau181p（P-tau）、淀粉样蛋白-β（Aβ）、结构 MRI 和神经心理学测试。同时对 20 名参与者进行了 11C-Pittsburgh 化合物 B PET。通过多元线性回归评估 18F-flortaucipir PET 与这些指标之间的关联，调整了潜在混杂因素，并使用全局、叶和体素标准化摄取比值（SUVr）。

结果

在调整年龄、性别、种族和教育程度后，全脑 18F-flortaucipir SUVr 与 CSF T-tau（r=0.68，p<0.001）和 P-tau（r=0.42，p=0.04）显著相关，在颞区的相关性最强（T-tau：r=0.69，p<0.001；P-tau：r=0.49，p=0.02）。体素分析证实了这些区域关联。18F-flortaucipir PET 还与 CSF Aβ（r=-0.45，p=0.03）、情节记忆（r=-0.61，p=0.001）、视觉空间工作记忆（r=-0.46，p=0.02）和脑皮质厚度（r=-0.44，p=0.03）相关，但与海马体积无关。在淀粉样蛋白 PET 亚组中，尽管 11C-PiB PET 与 18F-flortaucipir 高度相关（r=0.79，p≤0.001），但与关键结局相比，11C-PiB 与 18F-flortaucipir 之间的相关性更强。