German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Department of Radiology, University Hospital Bonn, Bonn, Germany.
J Alzheimers Dis. 2021;79(2):493-509. doi: 10.3233/JAD-200472.
Amyloid-β accumulation was found to alter precuneus-based functional connectivity (FC) in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia, but its impact is less clear in subjective cognitive decline (SCD), which in combination with AD pathologic change is theorized to correspond to stage 2 of the Alzheimer's continuum in the 2018 NIA-AA research framework.
This study addresses how amyloid pathology relates to resting-state fMRI FC in SCD, especially focusing on the precuneus.
From the DELCODE cohort, two groups of 24 age- and gender-matched amyloid-positive (SCDAβ+) and amyloidnegative SCD (SCDβ-) patients were selected according to visual [18F]-Florbetaben (FBB) PET readings, and studied with resting-state fMRI. Local (regional homogeneity [ReHo], fractional amplitude of low-frequency fluctuations [fALFF]) and global (degree centrality [DC], precuneus seed-based FC) measures were compared between groups. Follow-up correlation analyses probed relationships of group differences with global and precuneal amyloid load, as measured by FBB standard uptake value ratios (SUVR=⫖FBB).
ReHo was significantly higher (voxel-wise p < 0.01, cluster-level p < 0.05) in the bilateral precuneus for SCDAβ+patients, whereas fALFF was not altered between groups. Relatively higher precuneus-based FC with occipital areas (but no altered DC) was observed in SCDAβ+ patients. In this latter cluster, precuneus-occipital FC correlated positively with global (SCDAβ+) and precuneus SUVRFBB (both groups).
While partial confounding influences due to a higher APOE ε4 carrier ratio among SCDAβ+ patients cannot be excluded, exploratory results indicate functional alterations in the precuneus hub region that were related to amyloid-β load, highlighting incipient pathology in stage 2 of the AD continuum.
在轻度认知障碍（MCI）和阿尔茨海默病（AD）痴呆患者中，淀粉样蛋白-β的积累被发现改变了楔前叶的功能连接（FC），但在主观认知下降（SCD）中其影响尚不清楚，SCD 与 AD 病理变化相结合，被认为与 2018 年 NIA-AA 研究框架中的 AD 连续体的第 2 阶段相对应。
本研究旨在探讨 SCD 中淀粉样蛋白病理学与静息态 fMRI FC 的关系，特别是聚焦于楔前叶。
从 DELCODE 队列中，根据视觉[18F]-Florbetaben（FBB）PET 读数，选择了两组年龄和性别匹配的淀粉样蛋白阳性（SCDAβ+）和淀粉样蛋白阴性 SCD（SCDβ-）患者（每组 24 例），并进行了静息态 fMRI 研究。比较了两组之间的局部（局部一致性[ReHo]、低频波动幅度分数[fALFF]）和全局（度中心度[DC]、楔前叶种子基础 FC）测量值。随访相关性分析探测了组间差异与全球和楔前叶淀粉样蛋白负荷之间的关系，用 FBB 标准摄取值比值（SUVR=⫖FBB）进行测量。
SCDAβ+患者双侧楔前叶的 ReHo 显著升高（体素水平 p < 0.01，簇水平 p < 0.05），而两组间 fALFF 无差异。SCDAβ+患者观察到相对较高的楔前叶与枕叶区域的 FC（但 DC 无改变）。在后一个聚类中，楔前叶-枕叶 FC 与全局（SCDAβ+）和楔前叶 FBB SUVR 呈正相关（两组）。
虽然不能排除由于 SCDAβ+患者 APOE ε4 携带者比例较高而导致的部分混杂影响，但探索性结果表明楔前叶中枢区域的功能改变与淀粉样蛋白-β负荷有关，突出了 AD 连续体第 2 阶段的早期病理。
