Ghaderi Yazdi Bardiya, Razlighi Qolamreza R
Department of Radiology, Brain Health Imaging Institute, Weill Cornell Medicine, New York, NY, USA.
J Transl Med. 2025 Jul 29;23(1):850. doi: 10.1186/s12967-025-06721-x.
Aging, mild cognitive impairment (MCI), Alzheimer's disease (AD), and individuals at risk for AD are associated with impaired negative blood-oxygen-level-dependent (BOLD) response (NBR) in task-evoked functional magnetic resonance imaging (fMRI) studies. In addition, autosomal dominant AD patients have exhibited NBR alterations in the default mode network (DMN) regions nearly a decade before any accumulation of amyloid-β (Aβ) or tau and subsequent memory decline. Studies examining exclusively the NBR are rare in clinical settings, but some existing studies using task-evoked fMRI also report alterations in the NBR. However, in many studies, NBR is often disregarded, left lingering in the shadows, or, more generally, masked out as a bothersome noise.
We reviewed the Embase, Scopus, and PubMed databases, and forward and backward citation tracking for studies published up to 6/11/2024. Included articles detailed the use of task-evoked fMRI (tb-fMRI) to investigate aging, AD, mild cognitive impairment (MCI), and early tau or Aβ deposition, with all results reported on NBR.
From 319 records identified for aging, 154 records for tau or Aβ, and 159 records for AD and MCI, 42, 14, and 9 papers were included, respectively. Forward and backward citation tracking added 44, 3, and 55 papers, respectively resulting in 167 studies with 11310 individuals. A significantly reduced magnitude of NBR in some regions of the DMN in healthy aging compared with young participants and individuals with elevated Aβ levels, MCI, and AD compared to healthy aging was found in 57, 12, 17, and 14 studies, respectively.
This review highlights the DMN NBR's importance in the AD continuum and underscores its potential as an early diagnostic biomarker when pharmacological treatment options can still alter the disease course.
在任务诱发功能磁共振成像（fMRI）研究中，衰老、轻度认知障碍（MCI）、阿尔茨海默病（AD）以及有患AD风险的个体均与负性血氧水平依赖（BOLD）反应（NBR）受损有关。此外，常染色体显性AD患者在淀粉样β蛋白（Aβ）或tau蛋白出现任何累积以及随后出现记忆衰退的近十年前，其默认模式网络（DMN）区域就已表现出NBR改变。在临床环境中，专门研究NBR的研究很少，但一些使用任务诱发fMRI的现有研究也报告了NBR的改变。然而，在许多研究中，NBR常常被忽视，被搁置在阴影中，或者更普遍地说，被当作恼人的噪音而掩盖掉。
我们检索了Embase、Scopus和PubMed数据库，并对截至2024年11月6日发表的研究进行了前后向引文追踪。纳入的文章详细介绍了使用任务诱发fMRI（tb - fMRI）来研究衰老、AD、轻度认知障碍（MCI）以及早期tau或Aβ沉积的情况，所有结果均报告了NBR。
从为衰老、tau或Aβ、AD和MCI分别识别出的319条记录、154条记录和159条记录中，分别纳入了42篇、14篇和9篇论文。前后向引文追踪分别增加了44篇、3篇和55篇论文，最终得到167项研究，涉及11310名个体。分别在57项、12项、17项和14项研究中发现，与年轻参与者相比，健康衰老个体的DMN某些区域的NBR幅度显著降低；与健康衰老个体相比，Aβ水平升高、MCI和AD个体的DMN某些区域的NBR幅度也显著降低。
本综述强调了DMN的NBR在AD连续过程中的重要性，并强调了在药物治疗选择仍可改变疾病进程时，其作为早期诊断生物标志物的潜力。
