Beta amyloid (Aβ) accumulation is the earliest pathological marker of Alzheimer's disease (AD), but early AD pathology also affects white matter (WM) integrity. We performed a cross-sectional study including 44 subjects (23 healthy controls and 21 mild cognitive impairment or early AD patients) who underwent simultaneous PET-MR using 18F-Florbetapir, and were categorized into 3 groups based on Aβ burden: Aβ- [mean mSUVr ≤1.00], Aβi [1.00 < mSUVr <1.17], Aβ+ [mSUVr ≥1.17]. Intergroup comparisons of diffusion MRI metrics revealed significant differences across multiple WM tracts. Aβi group displayed more restricted diffusion (higher fractional anisotropy, radial kurtosis, axonal water fraction, and lower radial diffusivity) than both Aβ- and Aβ+ groups. This nonmonotonic trend was confirmed by significant continuous correlations between mSUVr and diffusion metrics going in opposite direction for 2 cohorts: pooled Aβ-/Aβi and pooled Aβi/Aβ+. The transient period of increased diffusion restriction may be due to inflammation that accompanies rising Aβ burden. In the later stages of Aβ accumulation, neurodegeneration is the predominant factor affecting diffusion.

中文翻译：

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白质微结构的扩散 MRI 生物标志物随着脑淀粉样蛋白沉积的增加而非单调变化


β淀粉样蛋白 (Aβ) 积累是阿尔茨海默病 (AD) 最早的病理标志物，但早期 AD 病理也会影响白质 (WM) 完整性。我们进行了一项横断面研究，包括 44 名受试者（23 名健康对照和 21 名轻度认知障碍或早期 AD 患者），他们使用 18F-Florbetapir 同时接受 PET-MR，并根据 Aβ 负荷分为 3 组：Aβ- [平均mSUVr ≤1.00]，Aβi [1.00 < mSUVr <1.17]，Aβ+ [mSUVr ≥1.17]。扩散 MRI 指标的组间比较揭示了多个 WM 束之间的显着差异。与 Aβ- 和 Aβ+ 组相比，Aβi 组表现出更受限的扩散（较高的各向异性分数、径向峰度、轴突水分数和较低的径向扩散率）。这种非单调趋势得到了 mSUVr 和扩散指标之间显着的连续相关性的证实，两个队列的方向相反：合并 Aβ-/Aβi 和合并 Aβi/Aβ+。扩散限制增加的短暂时期可能是由于伴随 Aβ 负荷增加的炎症所致。在Aβ积累的后期，神经变性是影响扩散的主要因素。