Mueller Susanne G
Dept of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
Neuroimage Clin. 2025 May 26;47:103810. doi: 10.1016/j.nicl.2025.103810.
Amyloid-β associated network hypersynchrony is an early manifestation of pre-clinical Alzheimer's Disease (AD). The overall goal was to investigate a. how TBI and PTSD influence hypersynchrony expression and b. how progressing gray matter atrophy affects hypersynchrony expression.
T1-weighted images, resting-state fMRIs and amyloid-β SUVRs were obtained from 234 DoD-ADNI subjects with or without TBI and/or PTSD. The denoised BOLD signal from 382 rois was extracted with CONN and dynamic resting state analysis was used to identify 8 states including one corresponding to a hypersynchrony state (HSS). SuStaIn with gray matter volumes and amyloid-β SUVR as inputs was used to identify 2 subtypes with progressive gray matter loss.
HSS dwell-time correlated positively with amyloid-β (Kendall tau = 0.125,p = 0.047) and tau Braak stage 5&6 SUVR (Kendall tau = 0.200,p = 0.035). TBI increased the likelihood to observe the HSS (81 % with vs. 18 % wo TBI p < 0.001) as did a diagnosis of PTSD (67.4 % with vs. 32.6 % wo PTSD, p = 0.003). The SuStaIn subtypes differed mostly by the timing of the amyloid-β build-up but not by atrophy pattern. Subtype 2 had higher amyloid-β loads and longer HSS dwell-times than subtype 1 that had higher CAPS scores than subtype 2. Gray matter atrophy did not influence HSS dwell-time.
TBI and PTSD increased the likelihood to observe HSS. HSS dwell time was determined by AD pathology severity. The subtype characteristics indicate that PTSD drives gray matter loss in subtype 1 and AD pathology that in subtype 2. Severity of gray matter atrophy influenced neither HSS occurrence nor intensity.
淀粉样蛋白β相关的网络超同步化是临床前阿尔茨海默病（AD）的早期表现。总体目标是研究：a. 创伤性脑损伤（TBI）和创伤后应激障碍（PTSD）如何影响超同步化表达；b. 灰质萎缩进展如何影响超同步化表达。
从234名有或无TBI和/或PTSD的国防部-阿尔茨海默病神经影像倡议（DoD-ADNI）受试者中获取T1加权图像、静息态功能磁共振成像（fMRI）和淀粉样蛋白β标准化摄取值比率（SUVR）。使用CONN提取来自382个感兴趣区（roi）去噪后的血氧水平依赖（BOLD）信号，并采用动态静息态分析来识别8种状态，包括一种对应超同步化状态（HSS）的状态。以灰质体积和淀粉样蛋白βSUVR作为输入，使用持续状态（SuStaIn）来识别2种伴有进行性灰质丢失的亚型。
HSS停留时间与淀粉样蛋白β呈正相关（肯德尔tau系数=0.125，p=0.047），与tau Braak分期5和6期的SUVR呈正相关（肯德尔tau系数=0.200，p=0.035）。TBI增加了观察到HSS的可能性（有TBI者为81%，无TBI者为18%，p<0.001），PTSD诊断也是如此（有PTSD者为67.4%，无PTSD者为32.6%，p=0.003）。SuStaIn亚型的主要差异在于淀粉样蛋白β积累的时间，而非萎缩模式。亚型2的淀粉样蛋白β负荷更高，HSS停留时间更长，而亚型1比亚型2有更高的临床医师专用创伤后应激障碍量表（CAPS）评分。灰质萎缩不影响HSS停留时间。
TBI和PTSD增加了观察到HSS的可能性。HSS停留时间由AD病理严重程度决定。亚型特征表明，PTSD导致亚型1中的灰质丢失，而AD病理导致亚型2中的灰质丢失。灰质萎缩的严重程度既不影响HSS的发生，也不影响其强度。
