Li Jie-Qiong, Song Jing-Hui, Suckling John, Wang Yan-Jiang, Zuo Chuan-Tao, Zhang Can, Gao Jing-, Song Yu-Qiang, Xie An-Mu, Tan Lan, Yu Jin-Tai
Hospital of Qingdao University.
University of Cambridge.
Res Sq. 2023 Mar 29:rs.3.rs-2744271. doi: 10.21203/rs.3.rs-2744271/v1.
According to the new 'AT(N)' system, those with a normal amyloid biomarker but with abnormal tauopathy or biomarkers of neurodegeneration or neuronal injury, have been labeled suspected non-Alzheimer's pathophysiology (SNAP). We aimed to estimate the long-term clinical and cognitive trajectories of SNAP individuals in non-demented elders and its comparison with individual in the Alzheimer's disease (AD) pathophysiology using 'AT(N)' system.
We included individuals with available baseline cerebrospinal fluid (CSF) Aβ (A), CSF phosphorylated tau examination (T) and 18F-uorodeoxyglucose PET or volumetric magnetic resonance imaging (N) from the Alzheimer's Disease Neuroimaging Initiative database. Longitudinal change in clinical outcomes are assessed using linear mixed effects models. Conversion risk from cognitively normal (CN) to cognitively impairment, and conversion from mild cognitive impairment (MCI) to dementia are assessed using multivariate Cox proportional hazard models.
Totally, 366 SNAP individuals were included (114 A-T-N-, 154 A-T + N-, 54 A-T-N + and 44 A-T + N+) of whom 178 were CN and 188 were MCI. Compared with A-T-N-, CN elders with A-T + N-, A-T-N + and A-T + N + had a faster rate of ADNI-MEM score decline. Moreover, CN older individuals with A-T + N + also had a faster rate of decline in ADNI-MEM score than those with A-T + N- individuals. MCI patients with A-T + N + had a faster rate of ADNI-MEM and ADNI-EF decline and hippocampal volume loss compared with A-T-N- and A-T + N- profiles. CN older individuals with A-T + N + had an increased risk of conversion to cognitive impairment (CDR-GS ≥ 0.5) compared with A-T + N- and A-T-N-. In MCI patients, A-T + N + also had an increased risk of conversion to dementia compared with A-T + N- and A-T-N-. Compared with A-T + N-, CN elders and MCI patients with A + T + N- and A + T + N + had a faster rate of ADNI-MEM score, ADNI-EF score decline, and hippocampal volume loss. CN individuals with A + T + N + had a faster rate of ADNI-EF score decline compare with A-T + N + individuals. Moreover, MCI patients with A + T + N + also had a faster rate of decline in ADNI-MEM score, ADNI-EF score and hippocampal volume loss than those with A-T + N + individuals.
The findings from clinical, imaging and biomarker studies on SNAP, and its comparison with AD pathophysiology offered an important foundation for future studies.
根据新的“AT(N)”系统，那些淀粉样蛋白生物标志物正常，但存在异常tau病变或神经退行性变或神经元损伤生物标志物的个体，被标记为疑似非阿尔茨海默病病理生理学（SNAP）。我们旨在评估非痴呆老年人中SNAP个体的长期临床和认知轨迹，并使用“AT(N)”系统将其与阿尔茨海默病（AD）病理生理学个体进行比较。
我们纳入了来自阿尔茨海默病神经影像倡议数据库的、有可用基线脑脊液（CSF）Aβ（A）、CSF磷酸化tau检测（T）以及18F-氟脱氧葡萄糖PET或容积磁共振成像（N）的个体。使用线性混合效应模型评估临床结局的纵向变化。使用多变量Cox比例风险模型评估从认知正常（CN）转换为认知障碍以及从轻度认知障碍（MCI）转换为痴呆的风险。
总共纳入了366名SNAP个体（114名A-T-N-型、154名A-T+N-型、54名A-T-N+型和44名A-T+N+型），其中178名是CN，188名是MCI。与A-T-N-型相比，A-T+N-型、A-T-N+型和A-T+N+型的CN老年人ADNI-MEM评分下降速度更快。此外，A-T+N+型的CN老年人ADNI-MEM评分下降速度也比A-T+N-型个体更快。与A-T-N-型和A-T+N-型相比，A-T+N+型的MCI患者ADNI-MEM和ADNI-EF下降速度更快，海马体积损失更大。与A-T+N-型和A-T-N-型相比，A-T+N+型的CN老年人转换为认知障碍（CDR-GS≥0.5）的风险增加。在MCI患者中，与A-T+N-型和A-T-N-型相比，A-T+N+型转换为痴呆的风险也增加。与A-T+N-型相比，A+T+N-型和A+T+N+型的CN老年人和MCI患者ADNI-MEM评分、ADNI-EF评分下降速度更快，海马体积损失更大。与A-T+N+型个体相比，A+T+N+型的CN个体ADNI-EF评分下降速度更快。此外，与A-T+N+型个体相比，A+T+N+型的MCI患者ADNI-MEM评分、ADNI-EF评分下降速度更快，海马体积损失更大。
关于SNAP的临床、影像学和生物标志物研究结果及其与AD病理生理学的比较为未来研究提供了重要基础。
