Vascular burden and Alzheimer disease pathologic progression
Vascular burden and Alzheimer disease pathologic progression
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DOI：
10.1212/wnl.0b013e31826c1b9d
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发表时间：
2012-09-01
期刊：
影响因子：
9.9
通讯作者：
Jagust, William J.
中科院分区：
文献类型：
--
作者：
Lo, Raymond Y.;Jagust, William J.
目的：研究血管对阿尔茨海默病（AD）生物标志物纵向变化的贡献：阿尔茨海默病神经影像学倡议是一项基于临床的纵向研究，在认知正常（NC）、轻度认知障碍（MCI）和轻度AD的参与者中反复测量CSF、PET和MRI生物标志物。有严重脑血管风险的参与者被排除在外。将心血管风险评分和MRI白色高信号（WMH）作为血管负荷的替代标志物。应用广义估计方程，血管负荷及其与时间（血管负荷x时间）或随时间变化的WMH的相互作用进入回归模型，以评估生物标志物的变化率是否被修改vascular burden.Results：心血管风险特征不能预测CSF β（42）-淀粉样蛋白，[F-18]氟脱氧葡萄糖（FDG）PET摄取和MRI海马萎缩的进展。更高的基线心血管风险或WMH通常与认知障碍相关，特别是执行功能差。WMH随时间增加，MCI和AD的速率比NC快。随时间变化的WMH增加与NC中执行功能下降更快和FDG摄取更低相关。另外，WMH与3组中的CSF和MRI生物标志物无关。这些结果在考虑APOE 4后保持不变。结论：WMH增加与衰老、糖代谢降低和执行功能下降有关，但不影响AD特异性病理进展，提示血管对痴呆的贡献可能是累加的，但不一定独立于淀粉样蛋白通路。神经病学（R）2012;79：1349-1355
Objective: To investigate the vascular contribution to longitudinal changes in Alzheimer disease (AD) biomarkers.Methods: The Alzheimer's Disease Neuroimaging Initiative is a clinic based, longitudinal study with CSF, PET, and MRI biomarkers repeatedly measured in participants with normal cognition (NC), mild cognitive impairment (MCI), and mild AD. Participants with severe cerebrovascular risks were excluded. Cardiovascular risk scores and MRI white matter hyperintensities (WMHs) were treated as surrogate markers for vascular burden. Generalized estimating equations were applied, and both vascular burden and its interaction with time (vascular burden x time) or time-varying WMHs were entered into regression models to assess whether biomarker rates of change were modified by vascular burden.Results: Cardiovascular risk profiles were not predictive of progression in CSF beta(42)-amyloid, [F-18]fluorodeoxyglucose (FDG) PET uptake, and MRI hippocampal atrophy. Greater baseline cardiovascular risks or WMHs were generally associated with cognitive impairment, particularly poor executive function. WMHs increased over time with a faster rate in MCI and AD than in NC. Increased time-varying WMH was associated with faster decline in executive function and lower FDG uptake in NC. Otherwise, WMH was not associated with CSF and MRI biomarkers in the 3 groups. These findings remained unchanged after accounting for APOE4.Conclusion: Increased WMHs are associated with aging, decreased glucose metabolism, and decline in executive function but do not affect AD-specific pathologic progression, suggesting that the vascular contribution to dementia is probably additive although not necessarily independent of the amyloid pathway. Neurology (R) 2012;79:1349-1355