Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea.
Alzheimers Res Ther. 2024 Mar 7;16(1):50. doi: 10.1186/s13195-024-01417-8.
Growing evidence suggests that not only cerebrovascular disease but also Alzheimer's disease (AD) pathological process itself cause cerebral white matter degeneration, resulting in white matter hyperintensities (WMHs). Some preclinical evidence also indicates that white matter degeneration may precede or affect the development of AD pathology. This study aimed to clarify the direction of influence between in vivo AD pathologies, particularly beta-amyloid (Aβ) and tau deposition, and WMHs through longitudinal approach.
Total 282 older adults including cognitively normal and cognitively impaired individuals were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. The participants underwent comprehensive clinical and neuropsychological assessment, [C] Pittsburgh Compound B PET for measuring Aβ deposition, [F] AV-1451 PET for measuring tau deposition, and MRI scans with fluid-attenuated inversion recovery image for measuring WMH volume. The relationships between Aβ or tau deposition and WMH volume were examined using multiple linear regression analysis. In this analysis, baseline Aβ or tau were used as independent variables, and change of WMH volume over 2 years was used as dependent variable to examine the effect of AD pathology on increase of WMH volume. Additionally, we set baseline WMH volume as independent variable and longitudinal change of Aβ or tau deposition for 2 years as dependent variables to investigate whether WMH volume could precede AD pathologies.
Baseline Aβ deposition, but not tau deposition, had significant positive association with longitudinal change of WMH volume over 2 years. Baseline WMH volume was not related with any of longitudinal change of Aβ or tau deposition for 2 years. We also found a significant interaction effect between baseline Aβ deposition and sex on longitudinal change of WMH volume. Subsequent subgroup analyses showed that high baseline Aβ deposition was associated with increase of WMH volume over 2 years in female, but not in male.
Our findings suggest that Aβ deposition accelerates cerebral WMHs, particularly in female, whereas white matter degeneration appears not influence on longitudinal Aβ increase. The results also did not support any direction of influence between tau deposition and WMHs.
越来越多的证据表明，不仅脑血管疾病，阿尔茨海默病（AD）的病理过程本身也会导致脑白质退化，从而导致脑白质高信号（WMHs）。一些临床前证据还表明，白质退化可能先于 AD 病理的发展，或影响其发展。本研究旨在通过纵向研究方法阐明 AD 病理，特别是β-淀粉样蛋白（Aβ）和tau 沉积与 WMHs 之间的影响方向。
共有 282 名认知正常和认知受损的老年人参与了这项研究，他们来自韩国脑老化研究早期诊断和预测阿尔茨海默病（KBASE）队列。参与者接受了全面的临床和神经心理学评估、[C]匹兹堡复合物 B PET 以测量 Aβ沉积、[F] AV-1451 PET 以测量 tau 沉积以及 MRI 扫描，包括液体衰减反转恢复图像以测量 WMH 体积。使用多元线性回归分析检查 Aβ或 tau 沉积与 WMH 体积之间的关系。在这项分析中，基线 Aβ或 tau 被用作自变量，而 WMH 体积在 2 年内的变化被用作因变量，以检查 AD 病理对 WMH 体积增加的影响。此外，我们将基线 WMH 体积作为自变量，将 Aβ或 tau 沉积在 2 年内的纵向变化作为因变量，以研究 WMH 体积是否可以先于 AD 病理。
基线 Aβ沉积，而不是 tau 沉积，与 2 年内 WMH 体积的纵向变化呈显著正相关。基线 WMH 体积与 2 年内 Aβ或 tau 沉积的纵向变化均无相关性。我们还发现基线 Aβ沉积与性别对 WMH 体积纵向变化的交互作用有显著影响。随后的亚组分析表明，高基线 Aβ沉积与女性 2 年内 WMH 体积的增加有关，但与男性无关。
我们的研究结果表明，Aβ 沉积加速了脑 WMHs，尤其是在女性中，而白质退化似乎对白质中 Aβ 的纵向增加没有影响。结果也不支持 tau 沉积与 WMHs 之间的任何影响方向。
