Cerebral Microbleeds, CSF p-Tau, and Cognitive Decline: Significance of Anatomic Distribution
Cerebral Microbleeds, CSF p-Tau, and Cognitive Decline: Significance of Anatomic Distribution
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DOI：
10.3174/ajnr.a4351
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发表时间：
2015-09-01
影响因子：
3.5
通讯作者：
Weiner, M. W.
中科院分区：
文献类型：
--
作者：
Chiang, G. C.;Hernandez, J. C. Cruz;Weiner, M. W.
背景和目的：脑微出血与衰老、高血压和阿尔茨海默病有关。脑叶分布中的微出血被认为反映了潜在的淀粉样血管病，而深部灰质和幕下脑中的微出血常见于高血压。然而，尚不清楚这两种分布中的微出血如何与阿尔茨海默病发病机制相关。本分析的目的是测试脑叶和深灰质/幕下微出血是否表现出与脑脊液淀粉样蛋白-β和磷酸化 tau 181 蛋白水平以及纵向认知能力下降的差异相关性。 材料和方法：来自阿尔茨海默病神经影像计划的总共 626 名受试者（151 名认知正常，389 名患有轻度认知障碍，86 名患有阿尔茨海默病）接受了 3T MR 成像和腰椎穿刺也包含在分析中。目视评估微出血的数量和位置。在调整协变量的同时，使用普通最小二乘、logistic 和混合效应回归模型评估脑叶或深灰/幕下微出血与 CSF β 淀粉样蛋白水平、异常 CSF 磷酸化 tau 181 蛋白水平和纵向认知能力下降之间的关联。结果：>= 3 次脑叶微出血与较低的 CSF 淀粉样蛋白 - 水平相关 (P = .001)。调整 CSF β 淀粉样蛋白水平后，脑叶微出血与 CSF 磷酸化 tau 181 蛋白水平异常的较高可能性独立相关 (P = .004)。脑叶微出血与纵向认知能力加速下降相关 (P = .007)。深灰色/幕下微出血没有显示出显着的关联。结论：微出血的分布揭示了与淀粉样β蛋白和磷酸化tau 181蛋白水平和认知的不同关联。关于阿尔茨海默病的发病机制，应分别考虑脑叶和深灰质/幕下微出血。
BACKGROUND AND PURPOSE: Cerebral microbleeds are associated with aging, hypertension, and Alzheimer disease. Microbleeds in a lobar distribution are believed to reflect underlying amyloid angiopathy, whereas microbleeds in the deep gray matter and infratentorial brain are commonly seen with hypertension. However, it is unknown how microbleeds in either distribution are related to Alzheimer pathogenesis. The purpose of this analysis was to test whether lobar and deep gray/infratentorial microbleeds demonstrate differential associations with CSF amyloid-beta and phosphorylated tau 181 protein levels and longitudinal cognitive decline.MATERIALS AND METHODS: A total of 626 subjects (151 cognitively normal, 389 with mild cognitive impairment, and 86 with Alzheimer disease) from the Alzheimer's Disease Neuroimaging Initiative who had undergone 3T MR imaging and lumbar puncture were included in the analysis. The number and location of microbleeds were assessed visually. Associations between lobar or deep gray/infratentorial microbleeds with CSF amyloid-beta levels, abnormal CSF phosphorylated tau 181 protein levels, and longitudinal cognitive decline were assessed by using ordinary least-squares, logistic, and mixed-effects regression models while adjusting for covariates.RESULTS: Having >= 3 lobar microbleeds was associated with lower levels of CSF amyloid-beta (P = .001). After adjusting for CSF amyloid-beta level, lobar microbleeds were independently associated with a higher likelihood of having an abnormal CSF phosphorylated tau 181 protein level (P = .004). Lobar microbleeds were associated with accelerated longitudinal cognitive decline (P = .007). Deep gray/infratentorial microbleeds revealed no significant associations.CONCLUSIONS: The distribution of microbleeds revealed different associations with amyloid-beta and phosphorylated tau 181 protein levels and cognition. Lobar and deep gray/infratentorial microbleeds should be considered separately with regard to Alzheimer disease pathogenesis.