Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
Douglas Mental Health University Institute, Montreal, Quebec, Canada.
JAMA Neurol. 2022 Oct 1;79(10):975-985. doi: 10.1001/jamaneurol.2022.2379.
National Institute on Aging-Alzheimer's Association (NIA-AA) workgroups have proposed biological research criteria intended to identify individuals with preclinical Alzheimer disease (AD).
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 β and tau positron emission tomography (PET). Median clinical follow-up after PET ranged from 1.94 to 3.66 years.
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+T+, A+T-, A-T+, A-T-). Presence (+) or absence (-) of neurodegeneration (N) was assessed using temporal cortical thickness.
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.
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.
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.
美国国家老龄化研究所-阿尔茨海默病协会（NIA-AA）工作组提出了旨在识别有临床前阿尔茨海默病（AD）的个体的生物研究标准。
评估这些生物标准在识别无认知障碍且近期有发生症状性 AD 风险的老年个体方面的临床价值。
设计、地点和参与者：本纵向队列研究使用了 4 个独立的基于人群的队列（PREVENT-AD、HABS、AIBL 和 Knight ADRC）在 2003 年至 2021 年期间收集的数据。参与者为无认知障碍且在淀粉样蛋白β和tau 正电子发射断层扫描（PET）后有 1 年或以上临床观察的老年人。PET 后中位临床随访时间为 1.94 至 3.66 年。
根据全球淀粉样蛋白负荷（A）和 tau PET 摄取的复合时间区域（T）的二进制评估，参与者被分为 4 组（A+T+、A+T-、A-T+、A-T-）。使用颞皮质厚度评估是否存在（+）或不存在（-）神经退行性变（N）。
每个队列均分别进行分析。主要结局是临床进展为轻度认知障碍（MCI），在 Knight ADRC 中以临床痴呆评定量表评分为 0.5 或更高，在其他队列中以共识委员会审查确定。临床评估者对成像、遗传和液体生物标志物数据不了解。次要结局是认知下降，基于独立无认知障碍亚组中个体的平均水平下降超过 1.5 个标准差。比较了生物标志物组之间的结局。
在 580 名参与者（PREVENT-AD，128；HABS，153；AIBL，48；Knight ADRC，251）中，年龄的平均值（标准差）在各队列中从 67（5）岁到 76（6）岁不等，女性参与者占 55%（137/251）至 74%（95/128）。在各队列中，与其他生物标志物组的参与者相比，A+T+参与者在随访期间进展为 MCI 的比例为 33%至 83%（平均进展时间为 2-2.72 年），而在其他生物标志物组中进展为 MCI 的比例不到 20%。当限制为 A+T+（N+）个体时，进展率进一步增加到 43%至 100%。与其他生物标志物组相比，A+T+组进展为 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下降，而其他组的认知轨迹则保持相对稳定。
在 4 个独立队列中证实了 NIA-AA 研究标准的临床预后价值，大多数无认知障碍且近期有发生 AD 症状风险的 A+T+（N+）老年个体在 2 至 3 年内出现 AD 症状。
