Cerebral Microbleeds, Cerebral Amyloid Angiopathy, and Their Relationships to Quantitative Markers of Neurodegeneration
Cerebral Microbleeds, Cerebral Amyloid Angiopathy, and Their Relationships to Quantitative Markers of Neurodegeneration
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DOI：
10.1212/wnl.0000000000200142
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发表时间：
2022-04-19
期刊：
影响因子：
9.9
通讯作者：
Gutierrez, Jose
中科院分区：
文献类型：
--
作者：
Beaman, Charles;Kozii, Krystyna;Gutierrez, Jose
背景和目的与年龄相关的认知障碍是由神经血管和神经退行性疾病的复杂相互作用引起的。脑微出血(CMBS)、脑淀粉样血管病(CAA)与阿尔茨海默病等疾病中观察到的认知能力下降有很强的相关性。然而，在认知障碍的早期临床前阶段，CMBS和潜在的CAA对与神经退行性疾病相关的大脑体积变化的影响程度尚不清楚。方法对曼哈顿北部研究(NOMAS)、阿尔茨海默病神经影像研究(ADNI)和新加坡痴呆症流行病学研究(EDIS)3个大队列进行横断面分析。我们对82例来自脑动脉重塑研究(BARS)的尸检病例进行了验证性分析。我们用多元回归分析来研究脑血管疾病的两个相关标记物-基于MRI的CMBS和基于尸检的CAA-作为自变量和神经变性的体积标记物作为因变量之间的关系。NOMA包括来自曼哈顿北部的55岁或55岁以上的无痴呆症参与者。ADNI包括居住在美国的参与者，年龄在55-90岁之间，认知状况各不相同。EDI包括居住在新加坡的社区参与者，年龄在60岁及以上，具有一系列认知状态。试纸包括死后病理标本。结果我们纳入了2657名有MRI数据的参与者和82例来自BARS的尸检案例。在对NOMAS、ADNI和EDI的Meta分析中，浅表CMBS与较大的灰质(β=4.49+/-1.13，p=0.04)和白质(β=4.72+/-2.1，p=0.03)体积相关。表浅CMBS与较大的白质体积之间的关联在有1个CMB的参与者中更明显(beta=5.17+/-2.47，p=0.04)，而在>；=2 CMBS的参与者中(beta=1.97+/-3.41，p=0.56)。在BAR中，CAA与皮质厚度增加(β=6.5+/-2.3，p=0.016)有关，但与脑重量增加(β=1.5 4+/-1.2 9，p=0.2 6)无关。讨论浅表CMBS与较大的脑形态测量指标相关，特别是脑白质体积。这种关联在CMBS较少的大脑中最强，这表明CMB/CAA对神经退化的贡献可能与组织丢失无关，至少在疾病的早期阶段是这样。
Background and Objectives Age-related cognitive impairment is driven by the complex interplay of neurovascular and neurodegenerative disease. There is a strong relationship between cerebral microbleeds (CMBs), cerebral amyloid angiopathy (CAA), and the cognitive decline observed in conditions such as Alzheimer disease. However, in the early, preclinical phase of cognitive impairment, the extent to which CMBs and underlying CAA affect volumetric changes in the brain related to neurodegenerative disease remains unclear. Methods We performed cross-sectional analyses from 3 large cohorts: The Northern Manhattan Study (NOMAS), Alzheimer's Disease Neuroimaging Initiative (ADNI), and the Epidemiology of Dementia in Singapore study (EDIS). We conducted a confirmatory analysis of 82 autopsied cases from the Brain Arterial Remodeling Study (BARS). We implemented multivariate regression analyses to study the association between 2 related markers of cerebrovascular disease-MRI-based CMBs and autopsy-based CAA-as independent variables and volumetric markers of neurodegeneration as dependent variables. NOMAS included mostly dementia-free participants age 55 years or older from northern Manhattan. ADNI included participants living in the United States age 55-90 years with a range of cognitive status. EDIS included community-based participants living in Singapore age 60 years and older with a range of cognitive status. BARS included postmortem pathologic samples. Results We included 2,657 participants with available MRI data and 82 autopsy cases from BARS. In a meta-analysis of NOMAS, ADNI, and EDIS, superficial CMBs were associated with larger gray matter (beta = 4.49 +/- 1.13, p = 0.04) and white matter (beta = 4.72 +/- 2.1, p = 0.03) volumes. The association between superficial CMBs and larger white matter volume was more evident in participants with 1 CMB (beta = 5.17 +/- 2.47, p = 0.04) than in those with >= 2 CMBs (beta = 1.97 +/- 3.41, p = 0.56). In BARS, CAA was associated with increased cortical thickness (beta = 6.5 +/- 2.3, p = 0.016) but not with increased brain weight (beta = 1.54 +/- 1.29, p = 0.26). Discussion Superficial CMBs are associated with larger morphometric brain measures, specifically white matter volume. This association is strongest in brains with fewer CMBs, suggesting that the CMB/CAA contribution to neurodegeneration may not relate to tissue loss, at least in early stages of disease.