Association of Superficial White Matter Microstructure With Cortical Pathology Deposition Across Early Stages of the AD Continuum

作者：Shuyue Wang, Fan Zhang, Qingze Zeng, Hui Hong, Yao Zhang, Linyun Xie, Lin Miao, Yeerfan Jiaerken, Xinfeng Yu, R. Zhang, Xiao Luo, Kaicheng Li, Xiaopei Xu, Shiva Hassanzadeh‐Behbahani, Bin Lin, Jarrett Rushmore, Chao Wang, Yogesh Rathi, Nikos Makris, Peiyu Huang, Minming Zhang, Jianzhong Sun, Lauren J. O’Donnell, for the Alzheimer's Disease Neuroimaging Initiative · 发表于：Neurology · 年份：2025 · DOI：10.1212/wnl.0000000000213666 · 被引用次数：11 · 研究领域：Advanced Neuroimaging Techniques and Applications、Dementia and Cognitive Impairment Research、Alzheimer's disease research and treatments

Background and Objectivesβ-amyloid (Aβ) and tau, 2 prominent pathologies of Alzheimer disease (AD), originate in cortical regions and primarily affect, and even spread along, the white matter tracts directly connected to these cortical regions. Superficial white matter (SWM), containing short-range association connections beneath the cortex, has been affected in mild cognitive impairment and AD, with gaps in understanding the disease's early stages. We perform a detailed investigation of individual SWM connections with cortical pathology deposition and cognition in the early stages of the AD continuum. MethodsWe enroll participants with Aβ PET, tau PET, diffusion MRI, and cognitive status from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Harvard Aging Brain Study (HABS). We stratify participants into disease stages following the Aβ/tau (AT) framework. We use diffusion MRI tractography to analyze SWM fiber clusters and assess their microstructure through free-water modeling, identifying significant differences between pathologically staged groups. We investigate associations of diffusion measures in SWM fiber clusters with regional pathology deposition (Aβ- and tau- PET uptake) and cognition. ResultsThe study includes 150 ADNI participants (mean age 73.6 years, 61.3% female) and 175 HABS participants (mean age 75.6 years, 61.1% female). We find the following: (1) SWM microstructure differs along the early-stage Alzheimer disease continuum, with primary abnormalit...