Association of Factors With Elevated Amyloid Burden in Clinically Normal Older Individuals
Association of Factors With Elevated Amyloid Burden in Clinically Normal Older Individuals
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DOI：
10.1001/jamaneurol.2020.0387
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发表时间：
2020-06-01
期刊：
影响因子：
29
通讯作者：
Aisen, Paul S.
中科院分区：
文献类型：
--
作者：
Sperling, Reisa A.;Donohue, Michael C.;Aisen, Paul S.
淀粉样蛋白沉积升高是否与人口统计学、遗传和生活方式因素有关？神经心理测试成绩下降；在临床上正常的老年人中，最近有越来越多的认知功能变化的报道？在对A4研究筛查人口统计学、认知和淀粉样蛋白正电子发射断层扫描数据的横断面分析中，淀粉样蛋白升高与较高的年龄、载脂蛋白E ε 4等位基因和家族史显著相关，但与性别、教育、婚姻或退休状况或多种自我报告的生活方式变量无关。淀粉样蛋白升高与临床前阿尔茨海默氏认知综合测试及其各组成部分的表现下降显著相关，并且与参与者及其研究伙伴近期高水平日常认知功能主观下降的报告增多有关。意味着淀粉样蛋白升高与认知能力下降和日常功能的细微变化有关，即使是在二级预防试验资格所需的正常表现限制范围内也是如此。抗淀粉样蛋白治疗无症状阿尔茨海默病（A4）研究是一项正在进行的预防试验，对象是有证据表明脑淀粉样蛋白升高的临床正常老年人。大量参与者通过淀粉样蛋白正电子发射断层扫描（PET）和标准化评估进行筛查，为评估与脑淀粉样蛋白升高相关的因素提供了前所未有的机会。目的探讨淀粉样蛋白升高与人口统计学和生活方式因素、载脂蛋白E （APOE）、神经心理测试以及自我和同伴认知功能报告的关系。本横断面研究包括2014年4月至2017年12月收集的无症状阿尔茨海默病抗淀粉样蛋白治疗（A4）研究中的筛选数据，并按淀粉样蛋白状态分类。研究人员分析了2018年至2019年美国、加拿大、澳大利亚和日本67个地点的数据，包括4486名符合淀粉样蛋白PET测试条件的老年人（65-85岁）（临床正常[临床痴呆评分= 0]和认知未受损[迷你精神状态检查评分，>= 25；逻辑记忆IIa 6-18]）。筛查人口统计学、生活方式变量、APOE基因分型、认知测试（临床前阿尔茨海默认知复合）、自我和研究伙伴报告的高水平日常认知功能（认知功能指数）。Florbetapir淀粉样蛋白PET成像用于将参与者分类为淀粉样蛋白升高（A β +）或没有淀粉样蛋白升高（A β -）。结果4486名参与者（平均[SD]年龄71.29[4.67]岁；2647名女性[59%]）获得淀粉样蛋白PET结果，其中1323名（29.5%）被分类为A β +。β +的参与者比β -的参与者年龄稍大，在性别、教育程度、婚姻或退休状况或任何自我报告的生活方式因素方面没有观察到差异。β +参与者更有可能有痴呆家族史（3320个A β +[74%]对3050个A β -[68%]）和至少1个APOE ε 4等位基因（2602个A β +[58%]对1122个A β -[25%]）。β +参与者在筛查临床前阿尔茨海默氏认知复合结果方面表现较差，在认知功能指数上报告了更高的变化得分。在一项针对老年痴呆症（AD）预防试验的大量老年人筛查中，脑淀粉样蛋白升高与家族史和APOE epsilon 4等位基因相关，但与其他多种先前报道的AD危险因素无关。淀粉样蛋白升高与较低的测试成绩和近期日常认知功能轻微下降的报告增加有关。这些结果支持了淀粉样蛋白升高代表阿尔茨海默病连续体早期阶段的假设，并证明了将这些高风险参与者纳入旨在减缓阿尔茨海默病临床前阶段认知能力下降的二级预防试验的可行性。本横断面分析研究了A4研究参与者中淀粉样蛋白升高与人口统计学和生活方式因素、载脂蛋白E、神经心理测试以及自我和研究伙伴的认知功能报告之间的关系。
Question Is elevated amyloid-beta deposition associated with demographic, genetic, and lifestyle factors; decreased performance on neuropsychological tests; and increased reports of recent changes in cognitive function among clinically normal older individuals? Findings In this cross-sectional analysis of the A4 Study screening demographic, cognitive and amyloid positron emission tomography data, elevated amyloid was significantly associated with higher age, apolipoprotein E epsilon 4 allele, and family history but not with sex, education, marital or retirement status, or multiple self-reported lifestyle variables. Elevated amyloid was significantly associated with lower performance on the Preclinical Alzheimer Cognitive Composite and each of its components, as well as with increased reports of recent subjective declines in high-level daily cognitive function by the participant and their study partner. Meaning Elevated amyloid is associated with worse cognition and subtle changes in daily function, even among the restricted range of normal performance required for eligibility in this secondary prevention trial.Importance The Anti-Amyloid Treatment in Asymptomatic Alzheimer disease (A4) Study is an ongoing prevention trial in clinically normal older individuals with evidence of elevated brain amyloid. The large number of participants screened with amyloid positron emission tomography (PET) and standardized assessments provides an unprecedented opportunity to evaluate factors associated with elevated brain amyloid. Objective To investigate the association of elevated amyloid with demographic and lifestyle factors, apolipoprotein E (APOE), neuropsychological testing, and self- and study partner reports of cognitive function. Design, Setting, and Participants This cross-sectional study included screening data in the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease (A4) Study collected from April 2014 to December 2017 and classified by amyloid status. Data were was analyzed from 2018 to 2019 across 67 sites in the US, Canada, Australia, and Japan and included 4486 older individuals (age 65-85 years) who were eligible for amyloid PET (clinically normal [Clinical Dementia Rating = 0] and cognitively unimpaired [Mini-Mental State Examination score, >= 25; logical memory IIa 6-18]). Main Outcomes and Measures Screening demographics, lifestyle variables, APOE genotyping, and cognitive testing (Preclinical Alzheimer Cognitive Composite), self- and study partner reports of high-level daily cognitive function (Cognitive Function Index). Florbetapir amyloid PET imaging was used to classify participants as having elevated amyloid (A beta+) or not having elevated amyloid (A beta-). Results Amyloid PET results were acquired for 4486 participants (mean [SD] age, 71.29 [4.67] years; 2647 women [59%]), with 1323 (29.5%) classified as A beta+. A beta+ participants were slightly older than A beta-, with no observed differences in sex, education, marital or retirement status, or any self-reported lifestyle factors. A beta+ participants were more likely to have a family history of dementia (3320 A beta+ [74%] vs 3050 A beta- [68%]) and at least 1 APOE epsilon 4 allele (2602 A beta+ [58%] vs 1122 A beta- [25%]). A beta+ participants demonstrated worse performance on screening Preclinical Alzheimer Cognitive Composite results and reported higher change scores on the Cognitive Function Index. Conclusions and Relevance Among a large group of older individuals screening for an Alzheimer disease (AD) prevention trial, elevated brain amyloid was associated with family history and APOE epsilon 4 allele but not with multiple other previously reported risk factors for AD. Elevated amyloid was associated with lower test performance results and increased reports of subtle recent declines in daily cognitive function. These results support the hypothesis that elevated amyloid represents an early stage in the Alzheimer continuum and demonstrate the feasibility of enrolling these high-risk participants in secondary prevention trials aimed at slowing cognitive decline during the preclinical stages of AD.This cross-sectional analysis examines the association of elevated amyloid with demographic and lifestyle factors, apolipoprotein E, neuropsychological testing, and self- and study partner reports of cognitive function among participants in the A4 Study.