阿尔茨海默病(AD)是一种普遍存在的神经退行性疾病,对全球公共卫生构成了挑战。神经影像学生物标志物将显著改善早期诊断和干预,最终提高受影响个人的生活质量,减轻医疗保健系统的负担。
■本研究使用了来自12个独立数据集的横截面和纵向数据(10,099名参与者,13,380次扫描)(本研究于2021年9月1日至2023年2月15日之间进行)。在基于结构MRI数据的集成机器学习模型下,通过基于区域和网络的综合措施开发了个体脑相关神经变性异常(IBRAIN)评分。我们系统地评估了IBRAIN是否可能是AD的神经影像学生物标志物。
■IBRAIN准确区分了患有AD的个体与NCs(AUC=0.92)和其他神经退行性疾病,包括额颞叶痴呆(FTD),帕金森病(PD),血管性痴呆(VaD)和肌萎缩侧索硬化(ALS)(AUC=0.92)。IBRAIN与临床测量和基因表达显着相关,丰富的免疫过程和蛋白质代谢。IBRAIN评分显示出明显的前驱AD进展能力(即,轻度认知障碍,MCI)(危险比(HR)=6.52[95%CI:4.42~9.62],p<1×10-16),与脑脊液(CSF)Aβ具有类似的强大性能(HR=3.78[95%CI:2.63~5.43],p=2.13×10-14)和CSFTau(HR=3.77[95%CI:2.64~5.39],p=9.53×10-15)基于COX和对数秩检验。值得注意的是,与CSFAβ(β=-0.26,p=4.40×10-9)和CSFTau(β=0.12,p=1.02×10-5)相比,IBRAIN在捕获转化为AD的个体的纵向变化方面显示出相当的敏感性(β=-0.70,p<1×10-16)。
■我们的研究结果表明,IBRAIN是生物学相关的,具体,和敏感的神经影像学生物标志物,可以作为一种临床措施来发现前驱AD进展。在未来的临床实践和治疗试验中具有很强的应用潜力。
■科技创新2030重大项目,国家自然科学基金,北京市自然科学基金,中央大学基础研究基金,和北京师范大学人才创业基金。
UNASSIGNED: Alzheimer\'s disease (AD) is a prevalent neurodegenerative disorder that poses a worldwide public health challenge. A neuroimaging biomarker would significantly improve early diagnosis and intervention, ultimately enhancing the quality of life for affected individuals and reducing the burden on healthcare systems.
UNASSIGNED: Cross-sectional and longitudinal data (10,099 participants with 13,380 scans) from 12 independent datasets were used in the present study (this study was performed between September 1, 2021 and February 15, 2023). The Individual Brain-Related Abnormalities In Neurodegeneration (IBRAIN) score was developed via integrated regional- and network-based measures under an ensemble machine learning model based on structural MRI data. We systematically assessed whether IBRAIN could be a neuroimaging biomarker for AD.
UNASSIGNED: IBRAIN accurately differentiated individuals with AD from NCs (AUC = 0.92) and other neurodegenerative diseases, including Frontotemporal dementia (FTD), Parkinson\'s disease (PD), Vascular dementia (VaD) and Amyotrophic Lateral Sclerosis (ALS) (AUC = 0.92). IBRAIN was significantly correlated to clinical measures and gene expression, enriched in immune process and protein metabolism. The IBRAIN score exhibited a significant ability to reveal the distinct progression of prodromal AD (i.e., Mild cognitive impairment, MCI) (Hazard Ratio (HR) = 6.52 [95% CI: 4.42∼9.62], p < 1 × 10-16), which offers similar powerful performance with Cerebrospinal Fluid (CSF) Aβ (HR = 3.78 [95% CI: 2.63∼5.43], p = 2.13 × 10-14) and CSF Tau (HR = 3.77 [95% CI: 2.64∼5.39], p = 9.53 × 10-15) based on the COX and Log-rank test. Notably, the IBRAIN shows comparable sensitivity (beta = -0.70, p < 1 × 10-16) in capturing longitudinal changes in individuals with conversion to AD than CSF Aβ (beta = -0.26, p = 4.40 × 10-9) and CSF Tau (beta = 0.12, p = 1.02 × 10-5).
UNASSIGNED: Our findings suggested that IBRAIN is a biologically relevant, specific, and sensitive neuroimaging biomarker that can serve as a clinical measure to uncover prodromal AD progression. It has strong potential for application in future clinical practice and treatment trials.
UNASSIGNED: Science and Technology Innovation 2030 Major Projects, the National Natural Science Foundation of China, Beijing Natural Science Funds, the Fundamental Research Funds for the CentralUniversity, and the Startup Funds for Talents at Beijing Normal University.