German Center for Neurodegenerative Diseases, Dresden, Germany.
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, LMU University Hospital Munich, Ludwig-Maximilians-Universität, Munich, Germany.
Alzheimers Res Ther. 2021 Jan 18;13(1):29. doi: 10.1186/s13195-020-00759-3.
White matter hyperintensities (WMH) are frequently found in Alzheimer's disease (AD). Commonly considered as a marker of cerebrovascular disease, regional WMH may be related to pathological hallmarks of AD, including beta-amyloid (Aβ) plaques and neurodegeneration. The aim of this study was to examine the regional distribution of WMH associated with Aβ burden, glucose hypometabolism, and gray matter volume reduction.
In a total of 155 participants (IMAP+ cohort) across the cognitive continuum from normal cognition to AD dementia, FLAIR MRI, AV45-PET, FDG-PET, and T1 MRI were acquired. WMH were automatically segmented from FLAIR images. Mean levels of neocortical Aβ deposition (AV45-PET), temporo-parietal glucose metabolism (FDG-PET), and medial-temporal gray matter volume (GMV) were extracted from processed images using established AD meta-signature templates. Associations between AD brain biomarkers and WMH, as assessed in region-of-interest and voxel-wise, were examined, adjusting for age, sex, education, and systolic blood pressure.
There were no significant associations between global Aβ burden and region-specific WMH. Voxel-wise WMH in the splenium of the corpus callosum correlated with greater Aβ deposition at a more liberal threshold. Region- and voxel-based WMH in the posterior corpus callosum, along with parietal, occipital, and frontal areas, were associated with lower temporo-parietal glucose metabolism. Similarly, lower medial-temporal GMV correlated with WMH in the posterior corpus callosum in addition to parietal, occipital, and fontal areas.
This study demonstrates that local white matter damage is correlated with multimodal brain biomarkers of AD. Our results highlight modality-specific topographic patterns of WMH, which converged in the posterior white matter. Overall, these cross-sectional findings corroborate associations of regional WMH with AD-typical Aß deposition and neurodegeneration.
脑白质高信号（WMH）在阿尔茨海默病（AD）中很常见。通常被认为是脑血管疾病的标志物，区域性 WMH 可能与 AD 的病理特征有关，包括β-淀粉样蛋白（Aβ）斑块和神经退行性变。本研究旨在检查与 Aβ 负荷、葡萄糖代谢低下和灰质体积减少相关的 WMH 的区域分布。
在认知连续体从正常认知到 AD 痴呆的 155 名参与者（IMAP+ 队列）中，进行了 FLAIR MRI、AV45-PET、FDG-PET 和 T1 MRI 采集。从 FLAIR 图像中自动分割 WMH。使用已建立的 AD 元特征模板，从处理后的图像中提取新皮质 Aβ 沉积（AV45-PET）、颞顶葡萄糖代谢（FDG-PET）和内侧颞叶灰质体积（GMV）的平均水平。在调整年龄、性别、教育和收缩压后，检查 AD 脑生物标志物与 WMH 在感兴趣区域和体素水平上的相关性。
全局 Aβ 负荷与特定区域的 WMH 之间没有显著相关性。胼胝体压部的体素水平 WMH 与更高的 Aβ 沉积相关，阈值更宽松。后部胼胝体、顶叶、枕叶和额叶区域的基于区域和体素的 WMH 与颞顶葡萄糖代谢低下相关。同样，后胼胝体的 WMH 与内侧颞叶 GMV 降低相关，此外还与顶叶、枕叶和额叶区域相关。
本研究表明局部白质损伤与 AD 的多模态脑生物标志物相关。我们的结果突出了 WMH 的特定模式模式，这些模式在后白质中汇聚。总体而言，这些横断面研究结果证实了区域性 WMH 与 AD 典型 Aβ 沉积和神经退行性变的相关性。
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