From the Department of Neurology (D.E.-L., J.K., L.C.S.), Veterans Affairs Medical Center, Portland, OR; and Departments of Neurology (D.E.-L., J.K., N.M., H.H.D., D.B.H., K.W., L.C.S.) and Pathology (R.W., S.G., H.T.), Oregon Health & Science University, Portland.
Neurology. 2013 Sep 10;81(11):977-83. doi: 10.1212/WNL.0b013e3182a43e45. Epub 2013 Aug 9.
To determine which vascular pathology measure most strongly correlates with white matter hyperintensity (WMH) accumulation over time, and whether Alzheimer disease (AD) neuropathology correlates with WMH accumulation.
Sixty-six older persons longitudinally followed as part of an aging study were included for having an autopsy and >1 MRI scan, with last MRI scan within 36 months of death. Mixed-effects models were used to examine the associations between longitudinal WMH accumulation and the following neuropathologic measures: myelin pallor, arteriolosclerosis, microvascular disease, microinfarcts, lacunar infarcts, large-vessel infarcts, atherosclerosis, neurofibrillary tangle rating, and neuritic plaque score. Each measure was included one at a time in the model, adjusted for duration of follow-up and age at death. A final model included measures showing an association with p < 0.1.
Mean age at death was 94.5 years (5.5 SD). In the final mixed-effects models, arteriolosclerosis, myelin pallor, and Braak score remained significantly associated with increased WMH accumulation over time. In post hoc analysis, we found that those with Braak score 5 or 6 were more likely to also have high atherosclerosis present compared with those with Braak score 1 or 2 (p = 0.003).
Accumulating white matter changes in advanced age are likely driven by small-vessel ischemic disease. Additionally, these results suggest a link between AD pathology and white matter integrity disruption. This may be due to wallerian degeneration secondary to neurodegenerative changes. Alternatively, a shared mechanism, for example ischemia, may lead to both vascular brain injury and neurodegenerative changes of AD. The observed correlation between atherosclerosis and AD pathology supports the latter.
确定哪种血管病理学指标与脑白质高信号（WMH）随时间的积累相关性最强，以及阿尔茨海默病（AD）病理学是否与 WMH 积累相关。
纳入 66 名作为衰老研究一部分的老年人，他们接受了尸检，并进行了多次 MRI 扫描，且最后一次 MRI 扫描距死亡时间在 36 个月内。采用混合效应模型来检验脑白质高信号随时间的纵向积累与以下神经病理学指标之间的相关性：髓鞘苍白、小动脉硬化、微血管疾病、微梗死、腔隙性梗死、大血管梗死、动脉粥样硬化、神经纤维缠结评分和神经原纤维缠结斑块评分。每次将一个指标纳入模型，调整随访时间和死亡时的年龄。最后一个模型纳入了与 p < 0.1 具有相关性的指标。
死亡时的平均年龄为 94.5 岁（5.5 岁标准差）。在最终的混合效应模型中，小动脉硬化、髓鞘苍白和 Braak 评分仍然与随时间增加的 WMH 积累显著相关。在事后分析中，我们发现 Braak 评分 5 或 6 的患者比 Braak 评分 1 或 2 的患者更有可能同时存在高度动脉粥样硬化（p = 0.003）。
高龄患者脑白质改变的积累可能是由小血管缺血性疾病驱动的。此外，这些结果表明 AD 病理学与脑白质完整性破坏之间存在联系。这可能是由于神经退行性改变导致的 Wallerian 变性。或者，缺血等共同机制可能导致血管性脑损伤和 AD 的神经退行性改变。观察到的动脉粥样硬化与 AD 病理学之间的相关性支持后者。
