背景根据新的\'AT(N)\'系统,那些具有正常淀粉样蛋白生物标志物但具有异常tau蛋白病变或神经变性或神经元损伤的生物标志物的人,已被标记为疑似非阿尔茨海默病病理生理学(SNAP)。我们旨在使用AT(N)系统估算非痴呆老年人SNAP个体的长期临床和认知轨迹,并将其与阿尔茨海默病(AD)病理生理学中的个体进行比较。方法我们纳入了基线脑脊液(CSF)Aβ(A)的个体,来自阿尔茨海默病神经影像学计划数据库的CSF磷酸化tau检查(T)和18F-氟代脱氧葡萄糖PET或体积磁共振成像(N)。使用线性混合效应模型评估临床结果的纵向变化。从认知正常(CN)到认知损伤的转化风险,使用多变量Cox比例风险模型评估从轻度认知障碍(MCI)到痴呆的转化。结果完全,包括366名SNAP个体(114A-T-N-,154A-T+N-,54A-T-N+和44A-T+N+),其中178个是CN,188个是MCI。与A-T-N-相比,CN长老与A-T+N-,A-T-N+和A-T+N+ADNI-MEM评分下降速度较快。此外,具有A-T+N+的CN老年个体的ADNI-MEM评分下降速度也快于具有A-T+N+的个体。与A-T-N和A-TN谱相比,A-TN+MCI患者的ADNI-MEM和ADNI-EF下降和海马体积损失的速率更快。与A-T+N和A-T-N相比,A-T+N+的CN老年个体转换为认知障碍(CDR-GS≥0.5)的风险增加。在MCI患者中,与A-TN-和A-T-N-相比,A-TN-转化为痴呆的风险也增加。与A-T+N-相比,CN老年人和MCI患者A+T+N和A+T+N有较快的ADNI-MEM评分,ADNI-EF评分下降,和海马体积损失。与A-T+N+个体相比,具有A+T+N+的CN个体具有更快的ADNI-EF评分下降速率。此外,A+T+N+的MCI患者ADNI-MEM评分下降速度也较快,ADNI-EF评分和海马体积损失均优于A-T+N+个体。结论来自临床的研究结果,SNAP的成像和生物标志物研究,其与AD病理生理学的比较为今后的研究提供了重要的基础。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: The findings from clinical, imaging and biomarker studies on SNAP, and its comparison with AD pathophysiology offered an important foundation for future studies.