Clinical Predictors of Severe Cerebral Amyloid Angiopathy and Influence of APOE Genotype in Persons With Pathologically Verified Alzheimer Disease
Clinical Predictors of Severe Cerebral Amyloid Angiopathy and Influence of APOE Genotype in Persons With Pathologically Verified Alzheimer Disease
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DOI：
10.1001/jamaneurol.2014.681
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发表时间：
2014-07-01
期刊：
影响因子：
29
通讯作者：
Vinters, Harry V.
中科院分区：
文献类型：
--
作者：
Ringman, John M.;Sachs, Michael C.;Vinters, Harry V.
尽管脑淀粉样血管病（CAA）具有重要的临床意义，但我们对其的认识和诊断能力有限。目的：确定预测病理证实的阿尔茨海默病（AD）患者存在严重CAA的病理相关因素和生活中可识别的临床因素。设计、环境和参与者我们比较了生命中最早就诊时发现认知障碍的患者的人口学和临床变量，并使用逻辑回归比较了尸检时最终发现没有或严重CAA的患者之间的病理变量。apoe4等位基因携带者和非携带者分别重复分析。数据来自统一数据集，该数据集包括由国家衰老研究所资助的阿尔茨海默病中心进行的纵向临床评估。参与者包括193例AD合并严重CAA患者和232例AD合并无CAA患者。所有的参与者都有认知障碍，并符合国家衰老研究所-里根研究所AD的神经病理标准。主要结果和测量：人口学特征和APOE ε 4等位基因的患病率以及预测严重CAA的临床变量的比值比（ORs）。结果严重的创新艺人经纪公司的人相比,那些没有创新艺人经纪公司更有可能携带一个APOEε4等位基因(分别为64.9%和42.8%;P <措施),是西班牙裔(分别为6.8%和1.3%;P = .003),有短暂性脑缺血发作(分别为12.5%和6.1%;或= 2.1;95%可信区间,1.0 - -4.4),和较低程度的扩散淀粉样斑块病理(意思是(SD)财团建立注册为阿尔茨海默病得分,1.2(0.5)和1.4(0.8),分别;P = . 01)。与没有CAA的患者相比，CAA患者更常发生脑出血（分别为9.3%对3.5%,P = 0.01）、皮质微梗死（分别为20.7%对12.9%,P = 0.03）和皮质下白质脑病（分别为20.5%对12.1%,P = 0.02）。患有严重CAA的APOE ε 4等位基因的非携带者与没有CAA的患者相比，卒中患病率更高（分别为11.1%对3.9%;OR = 3.8; 95% CI, 1.0-14.6）和高胆固醇血症（分别为50.0%对32.7%;OR = 2.3; 95% CI, 1.1-4.7）。西班牙裔和有过短暂性脑缺血发作样发作是AD患者CAA的预测因素。严重CAA患者较少弥漫性实质淀粉样蛋白病理提示β -淀粉样蛋白运输的差异。
IMPORTANCE Although cerebral amyloid angiopathy (CAA) has important clinical implications, our understanding of it and ability to diagnose it are limited.OBJECTIVE To determine pathological correlates and clinical factors identifiable during life that predict the presence of severe CAA in persons with pathologically confirmed Alzheimer disease (AD).DESIGN, SETTING, AND PARTICIPANTS We compared demographic and clinical variables at the earliest visit during life at which participants were found to have cognitive impairment and compared pathological variables between persons ultimately found to have no or severe CAA at autopsy using logistic regression. Analyses were repeated separately for carriers and noncarriers of the APOE 4 allele. Data were obtained from the Uniform Data Set, which comprises longitudinal clinical assessments performed in the Alzheimer's Disease Centers funded by the National Institute on Aging. Participants included 193 persons with AD and severe CAA and 232 persons with AD and no CAA. All participants had cognitive impairment and met National Institute on Aging-Reagan Institute neuropathological criteria for AD.MAIN OUTCOMES AND MEASURES Prevalence of demographic characteristics and the APOE epsilon 4 allele and odds ratios (ORs) of clinical variables for the prediction of severe CAA.RESULTS Persons with severe CAA compared with those without CAA were more likely to carry an APOE epsilon 4 allele (64.9% vs 42.8%, respectively; P < .001), to be Hispanic (6.8% vs 1.3%, respectively; P = .003), to have had a transient ischemic attack (12.5% vs 6.1%, respectively; OR = 2.1; 95% CI, 1.0-4.4), and to have lower degrees of diffuse amyloid plaque pathology (mean [SD] Consortium to Establish a Registry for Alzheimer's Disease score, 1.2 [0.5] vs 1.4 [0.8], respectively; P = .01). Those with CAA compared with those without CAA more commonly had intracerebral hemorrhage (9.3% vs 3.5%, respectively; P = .01), cortical microinfarcts (20.7% vs 12.9%, respectively; P = .03), and subcortical leukoencephalopathy (20.5% vs 12.1%, respectively; P = .02). Noncarriers of the APOE epsilon 4 allele with severe CAA compared with those without CAA had a higher prevalence of stroke (11.1% vs 3.9%, respectively; OR = 3.8; 95% CI, 1.0-14.6) and hypercholesterolemia (50.0% vs 32.7%, respectively; OR = 2.3; 95% CI, 1.1-4.7).CONCLUSIONS AND RELEVANCE Being Hispanic and having had a transient ischemic attack-like episode were predictors of CAA in persons with AD. Less diffuse parenchymal amyloid pathology in persons with severe CAA suggests a difference in beta-amyloid trafficking.