经病理证实的阿尔茨海默病患者中重度脑淀粉样血管病的临床预测因素及 APOE 基因型的影响
Clinical predictors of severe cerebral amyloid angiopathy and influence of APOE genotype in persons with pathologically verified Alzheimer disease.
作者信息
Ringman John M, Sachs Michael C, Zhou Yan, Monsell Sarah E, Saver Jeffrey L, Vinters Harry V
机构信息
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles2Mary S. Easton Center for Alzheimer's Disease Research, University of California, Los Angeles.
National Alzheimer's Coordinating Center, University of Washington, Seattle.
出版信息
JAMA Neurol. 2014 Jul 1;71(7):878-83. doi: 10.1001/jamaneurol.2014.681.
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 ε4 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 ε4 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 ε4 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 ε4 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 β-amyloid trafficking.
重要性
尽管脑淀粉样血管病（CAA）具有重要的临床意义，但我们对其的理解和诊断能力有限。
目的
确定在有病理确诊的阿尔茨海默病（AD）患者中，生前可识别的预测严重CAA存在的病理相关因素和临床因素。
设计、设置和参与者：我们比较了参与者在被发现有认知障碍的首次就诊时的人口统计学和临床变量，并使用逻辑回归比较了尸检时最终被发现无CAA或有严重CAA的患者之间的病理变量。对APOE ε4等位基因的携带者和非携带者分别重复进行分析。数据来自统一数据集，该数据集包括在美国国立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例患有AD和严重CAA的患者以及232例患有AD但无CAA的患者。所有参与者均有认知障碍，并符合美国国立衰老研究所 - 里根研究所AD的神经病理学标准。
主要结局和指标
人口统计学特征和APOE ε4等位基因的患病率以及预测严重CAA的临床变量的优势比（OR）。
结果
与无CAA的患者相比，患有严重CAA的患者更有可能携带APOE ε4等位基因（分别为64.9%和42.8%；P <.001），为西班牙裔（分别为6.8%和1.3%；P =.003），曾有短暂性脑缺血发作（分别为12.5%和6.1%；OR = 2.1；95% CI，1.0 - 4.4），并且弥漫性淀粉样斑块病理程度较低（平均[标准差]阿尔茨海默病注册协会评分，分别为1.2 [0.5]和1.4 [0.8]；P =.01）。与无CAA的患者相比，患有CAA的患者更常见脑出血（分别为9.3%和3.5%；P =.01）、皮质微梗死（分别为20.7%和12.9%；P =.03）和皮质下白质脑病（分别为20.5%和12.1%；P =.02）。与无CAA的患者相比，APOE ε4等位基因非携带者中患有严重CAA的患者中风患病率更高（分别为11.1%和3.9%；OR = 3.8；95% CI，1.0 - 14.6）和高胆固醇血症患病率更高（分别为50.0%和32.7%；OR = 2.
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