Association of Elevated Amyloid and Tau Positron Emission Tomography Signal With Near-Term Development of Alzheimer Disease Symptoms in Older Adults Without Cognitive Impairment
Association of Elevated Amyloid and Tau Positron Emission Tomography Signal With Near-Term Development of Alzheimer Disease Symptoms in Older Adults Without Cognitive Impairment
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DOI：
10.1001/jamaneurol.2022.2379
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发表时间：
2022-07-30
期刊：
影响因子：
29
通讯作者：
Villeneuve, Sylvia
中科院分区：
文献类型：
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作者：
Strikwerda-Brown, Cherie;Hobbs, Diana A.;Villeneuve, Sylvia
重要性 美国国家老龄化研究所 - 阿尔茨海默病协会 (NIA-AA) 工作组提出了生物学研究标准，旨在识别患有临床前阿尔茨海默病 (AD) 的个体。 目的 评估这些生物学标准的临床价值，以识别无认知障碍但近期有患 AD 症状风险的老年人。 设计、环境和参与者 这项纵向队列研究使用了来自 4 个独立的基于人群的队列（预防 AD、HABS、 AIBL 和 Knight ADRC）在 2003 年至 2021 年间收集。参与者是没有认知障碍的老年人，在 β 淀粉样蛋白和 tau 蛋白正电子发射断层扫描 (PET) 后进行了 1 年或更长时间的临床观察。 PET 后的中位临床随访时间为 1.94 至 3.66 年。 暴露 根据整体淀粉样蛋白负荷 (A) 和 tau PET 摄取复合颞区 (T) 的二元评估，参与者被分为 4 组（A+7+、A+T-、A-T+、A-T-）。使用颞叶皮质厚度评估神经退行性变（N）的存在（+）或不存在（-）。 主要结果和措施 每个队列均单独分析。主要结局是临床进展为轻度认知障碍 (MCI)，由 Knight ADRC 的临床痴呆评分为 0.5 或更高以及其他队列的共识委员会审查确定。临床评估者对影像、遗传和液体生物标志物数据视而不见。次要结果是认知能力下降，其斜率比没有认知障碍的独立子样本的平均值低 1.5 个标准差以上。比较不同生物标志物组的结果。 结果 在 580 名参与者（PREVENT-AD，128；HABS，153；AIBL，48；Knight ADRC，251）中，各队列的平均 (SD) 年龄范围为 67 (5) 至 76 (6) 岁，其中 55% (137/251) 至 74% (95/128) 为女性参与者。在各个队列中，33% 至 83% 的 A+T+ 参与者在随访期间进展为 MCI（平均进展时间为 2-2.72 年），而其他生物标志物组的参与者这一比例不到 20%。当仅限于 A+T+(N+) 个体时，进展进一步增加至 43% 至 100%。 A+T+ 组与其他生物标志物组相比进展为 MCI 的 Cox 比例风险比均为 5 或更高。许多 A+T+ 非进展者也表现出纵向认知衰退，而其他组的认知轨迹基本保持稳定。 结论和相关性 NIA-AA 研究标准的临床预后价值在 4 个独立队列中得到证实，大多数无认知障碍的 A+T+(N+) 老年人在 2 至 3 年内出现 AD 症状。
IMPORTANCE National Institute on Aging-Alzheimer's Association (NIA-AA) workgroups have proposed biological research criteria intended to identify individuals with preclinical Alzheimer disease (AD).OBJECTIVE To assess the clinical value of these biological criteria to identify older individuals without cognitive impairment who are at near-term risk of developing symptomatic AD.DESIGN, SETTING, AND PARTICIPANTS This longitudinal cohort study used data from 4 independent population-based cohorts (PREVENT-AD, HABS, AIBL, and Knight ADRC) collected between 2003 and 2021. Participants were older adults without cognitive impairment with 1 year or more of clinical observation after amyloid beta and tau positron emission tomography (PET). Median clinical follow-up after PET ranged from 1.94 to 3.66 years.EXPOSURES Based on binary assessment of global amyloid burden (A) and a composite temporal region of tau PET uptake (T), participants were stratified into 4 groups (A+7+, A+T-, A-T+, A-T-). Presence (+) or absence (-) of neurodegeneration (N) was assessed using temporal cortical thickness.MAIN OUTCOMES AND MEASURES Each cohort was analyzed separately. Primary outcome was clinical progression to mild cognitive impairment (MCI), identified by a Clinical Dementia Rating score of 0.5 or greater in Knight ADRC and by consensus committee review in the other cohorts. Clinical raters were blind to imaging, genetic, and fluid biomarker data. A secondary outcome was cognitive decline, based on a slope greater than 1.5 SD below the mean of an independent subsample of individuals without cognitive impairment. Outcomes were compared across the biomarker groups.RESULTS Among 580 participants (PREVENT-AD, 128; HABS, 153; AIBL, 48; Knight ADRC, 251), mean (SD) age ranged from 67 (5) to 76 (6) years across cohorts, with between 55% (137/251) and 74% (95/128) female participants. Across cohorts, 33% to 83% of A+T+ participants progressed to MCI during follow-up (mean progression time, 2-2.72 years), compared with less than 20% of participants in other biomarker groups. Progression further increased to 43% to 100% when restricted to A+T+(N+) individuals. Cox proportional hazard ratios for progression to MCI in the A+T+ group vs other biomarker groups were all 5 or greater. Many A+T+ nonprogressors also showed longitudinal cognitive decline, while cognitive trajectories in other groups remained predominantly stable.CONCLUSIONS AND RELEVANCE The clinical prognostic value of NIA-AA research criteria was confirmed in 4 independent cohorts, with most A+T+(N+) older individuals without cognitive impairment developing AD symptoms within 2 to 3 years.