Associations of Amyloid, Tau, and Neurodegeneration Biomarker Profiles With Rates of Memory Decline Among Individuals Without Dementia
Associations of Amyloid, Tau, and Neurodegeneration Biomarker Profiles With Rates of Memory Decline Among Individuals Without Dementia
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DOI：
10.1001/jama.2019.7437
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发表时间：
2019-06-18
影响因子：
120.7
通讯作者：
Petersen, Ronald C.
中科院分区：
文献类型：
--
作者：
Jack, Clifford R., Jr.;Wiste, Heather J.;Petersen, Ronald C.
重要性国家老龄化研究所和阿尔茨海默氏症协会提出了一个阿尔茨海默病的研究框架，其中研究参与者的生物标志物分类被标记为淀粉样蛋白、tau蛋白和神经变性生物标志物的AT（N）。设计、设置和参与者：明尼苏达州奥姆斯特德县认知老化的基于人群的队列研究，包括480名非痴呆的马约诊所老年研究参与者，他们进行了临床评估和淀粉样蛋白正电子发射断层扫描（PET）（A），在2015年4月16日至2017年11月1日期间测量tau PET（T）和磁共振成像（MRI）皮质厚度（N），并在2018年11月12日之前进行至少1次临床评价随访。A、T或（N）中的每一个都可以是异常（+）或正常（-），导致8个AT（N）profile.Main Outcomes AND Measures主要结果和测量主要结果是以15个月的间隔纵向测量的复合记忆评分。分析测量了预测变量和记忆评分之间的关联，以及AT（N）生物标志物谱是否显著改善了记忆Z评分变化率的预测，超过了仅具有临床和遗传变量的模型。结果参与者的中位随访时间为4.8年（四分位距[IQR]，3.8-5.1），44%为女性（211/480）。中位（IQR）年龄范围为A-T-（N）-组67岁（65-73岁）至A+T+（N）+组83岁（76-87岁）。在参与者中，92%（441/480）的认知未受损，但A+T+（N）+组的轻度认知障碍比例最大（30%）。AT（N）生物标志物改善了对临床模型记忆表现的预测，从0.26的R-2提高到0.31（P
IMPORTANCE A National Institute on Aging and Alzheimer's Association workgroup proposed a research framework for Alzheimer disease in which biomarker classification of research participants is labeled AT(N) for amyloid, tau, and neurodegeneration biomarkers.OBJECTIVE To determine the associations between AT(N) biomarker profiles and memory decline in a population-based cohort of individuals without dementia age 60 years or older, and to determine whether biomarkers provide incremental prognostic value beyond more readily available clinical and genetic information.DESIGN, SETTING, AND PARTICIPANTS Population-based cohort study of cognitive aging in Olmsted County, Minnesota, that included 480 nondemented Mayo Clinic Study of Aging participants who had a clinical evaluation and amyloid positron emission tomography (PET) (A), tau PET (T), and magnetic resonance imaging (MRI) cortical thickness (N) measures between April 16, 2015, and November 1, 2017, and at least 1 clinical evaluation follow-up by November 12, 2018.EXPOSURES Age, sex, education, cardiovascular and metabolic conditions score, APOE genotype, and AT(N) biomarker profiles. Each of A, T, or (N) can be abnormal (+) or normal (-), resulting in 8 AT(N) profiles.MAIN OUTCOMES AND MEASURES Primary outcomewas a composite memory score measured longitudinally at 15-month intervals. Analyses measured the associations between predictor variables and the memory score, and whether AT(N) biomarker profiles significantly improved prediction of memory z score rates of change beyond a model with clinical and genetic variables only. RESULTS Participants were followed up for a median of 4.8 years (interquartile range [IQR], 3.8-5.1) and 44% were women (211/480). Median (IQR) ages ranged from 67 years (65-73) in the A-T-(N)-group to 83 years (76-87) in the A+T+(N)+group. Of the participants, 92% (441/480) were cognitively unimpaired but the A+T+(N)+group had the largest proportion of mild cognitive impairment (30%). AT(N) biomarkers improved the prediction of memory performance over a clinical model from an R-2 of 0.26 to 0.31 (P