Dementia Research Centre, Department of Neurodegenerative Disease, University College London Institute of Neurology, London, UK.
Neurobiol Aging. 2013 Aug;34(8):1996-2002. doi: 10.1016/j.neurobiolaging.2013.02.003. Epub 2013 Mar 21.
This study assessed relationships among white matter hyperintensities (WMH), cerebrospinal fluid (CSF), Alzheimer's disease (AD) pathology markers, and brain volume loss. Subjects included 197 controls, 331 individuals with mild cognitive impairment (MCI), and 146 individuals with AD with serial volumetric 1.5-T MRI. CSF Aβ1-42 (n = 351) and tau (n = 346) were measured. Brain volume change was quantified using the boundary shift integral (BSI). We assessed the association between baseline WMH volume and annualized BSI, adjusting for intracranial volume. We also performed multiple regression analyses in the CSF subset, assessing the relationships of WMH and Aβ1-42 and/or tau with BSI. WMH burden was positively associated with BSI in controls (p = 0.02) but not MCI or AD. In multivariable models, WMH (p = 0.003) and Aβ1-42 (p = 0.001) were independently associated with BSI in controls; in MCI Aβ1-42 (p < 0.001) and tau (p = 0.04) were associated with BSI. There was no evidence of independent effects of WMH or CSF measures on BSI in AD. These data support findings that vascular damage is associated with increased brain atrophy in the context of AD pathology in pre-dementia stages.
本研究评估了脑白质高信号（WMH）、脑脊液（CSF）、阿尔茨海默病（AD）病理标志物与脑容量损失之间的关系。研究对象包括 197 名对照者、331 名轻度认知障碍（MCI）患者和 146 名 AD 患者，所有患者均接受了连续的 1.5-T MRI 容积成像。测量了 CSF 中的 Aβ1-42（n = 351）和 tau（n = 346）。采用边界位移积分（BSI）定量评估脑容量变化。我们评估了基线 WMH 体积与年度 BSI 的相关性，调整了颅内体积。我们还在 CSF 亚组中进行了多元回归分析，评估了 WMH 与 Aβ1-42 和/或 tau 与 BSI 的关系。在对照组中，WMH 负担与 BSI 呈正相关（p = 0.02），但在 MCI 或 AD 患者中不相关。在多变量模型中，WMH（p = 0.003）和 Aβ1-42（p = 0.001）与对照组的 BSI 独立相关；在 MCI 中，Aβ1-42（p < 0.001）和 tau（p = 0.04）与 BSI 相关。AD 患者中，WMH 或 CSF 标志物对 BSI 无独立影响的证据。这些数据支持血管损伤与 AD 病理相关的痴呆前阶段脑萎缩增加相关的发现。
