Abstract

Purpose

[¹⁸F]MK-6240, a second-generation tau PET tracer, is increasingly used for the detection and the quantification of in vivo cerebral tauopathy in Alzheimer’s disease (AD). Given that neurological symptoms are better explained by the topography rather than by the nature of brain lesions, our study aimed to evaluate whether cognitive impairment would be more closely associated with the spatial extent than with the intensity of tau-PET signal, as measured by the standard uptake value ratio (SUVr).

Methods

[¹⁸F]MK6240 tau-PET data from 82 participants in the AD spectrum were quantified in three different brain regions (Braak ≤ 2, Braak ≤ 4, and Braak ≤ 6) using SUVr and the extent of tauopathy (EOT, percentage of voxels with SUVr ≥ 1.3). PET data were first compared between diagnostic categories, and ROC curves were computed to evaluate sensitivity and specificity. PET data were then correlated to cognitive performances and cerebrospinal fluid (CSF) tau values.

Results

The EOT in the Braak ≤ 2 region provided the highest diagnostic accuracies, distinguishing between amyloid-negative and positive clinically unimpaired individuals (threshold = 9%, sensitivity = 79%, specificity = 82%) as well as between prodromal AD and preclinical AD (threshold = 38%, sensitivity = 81%, specificity = 93%). The EOT better correlated with cognition than SUVr (∆R² + 0.08–0.09) with the best correlation observed for EOT in the Braak ≤ 4 region (R² = 0.64). Cognitive performances were more closely associated with PET metrics than with CSF values.

Conclusions

Quantifying [¹⁸F]MK-6240 tau PET in terms of EOT rather than SUVr significantly increases the correlation with cognitive performances. Quantification in the mesiotemporal lobe is the most useful to diagnose preclinical AD or prodromal AD.

中文翻译：

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[18F]MK-6240 tau PET 上的 tau 蛋白病的空间范围显示，与阿尔茨海默氏病的标准摄取值比率相比，与认知表现的相关性更强

摘要

目的

[ ¹⁸ F]MK-6240 是第二代 tau PET 示踪剂，越来越多地用于阿尔茨海默病 (AD) 体内脑 tau 病的检测和定量。鉴于神经系统症状可以通过地形而不是脑损伤的性质来更好地解释，我们的研究旨在评估认知障碍是否与空间范围比与 tau-PET 信号强度更密切相关，该信号通过标准摄取值比（SUVr）。

方法

[ ¹⁸ F]MK6240 tau-PET 数据来自 82 名 AD 谱系参与者，使用 SUVr 和 tau 蛋白病变程度（EOT、体素百分比）在三个不同的大脑区域（Braak  ≤  2、Braak  ≤  4和Braak  ≤  6）进行量化SUVr ≥ 1.3）。首先比较诊断类别之间的 PET 数据，并计算 ROC 曲线以评估敏感性和特异性。然后将 PET 数据与认知表现和脑脊液 (CSF) tau 值相关联。

结果

Braak  ≤  2区域的 EOT提供了最高的诊断准确性，区分淀粉样蛋白阴性和阳性临床未受损个体（阈值 = 9%，敏感性 = 79%，特异性 = 82%）以及前驱 AD 和临床前 AD（阈值 = 38%，敏感性 = 81%，特异性 = 93%）。EOT 与认知的相关性优于 SUVr (ΔR ^{2 + 0.08–0.09)，在}Braak  ≤  4区域 观察到 EOT 的最佳相关性( R ²  = 0.64)。认知表现与 PET 指标的关系比与 CSF 值的关系更密切。

结论

根据 EOT 而不是 SUVr量化 [ ^{18 F]MK-6240 tau PET 显着增加了与认知表现的相关性。}颞叶内侧定量对于诊断临床前 AD 或前驱 AD 最有用。