Zhao Simin, Nie Yuting, Wen Lulu, Qin Xinzuo, Huang Liyuan, Chu Changbiao, Qu Miao
Third Clinical Medical College of Beijing University of Chinese Medicine, Beijing, China.
The Department of Neurology, Gansu Provincial Hospital, Lanzhou, China.
Front Neurosci. 2025 Apr 30;19:1587702. doi: 10.3389/fnins.2025.1587702. eCollection 2025.
Increased extracellular free water (FW) is considered to provide better pathophysiological information than conventional diffusion tensor imaging (DTI) metrics. The cholinergic brain network is a key hub for cognitive function, and microstructural changes detected by free water imaging in this system may be associated with cognitive impairment in Alzheimer's disease (AD). However, the specific impact of FW changes in the cholinergic brain network on cognitive domains across the AD continuum and their diagnostic value remain unclear.
Here, we investigated the basal forebrain cholinergic free water alterations based on free water-corrected diffusion tensor imaging in healthy controls ( = 36), amnestic mild cognitive impairment (aMCI; = 31), the AD group ( = 33). The cholinergic basal forebrain subregions were divided into the Broca diagonal band (Ch1-3) and the Meynert basal nucleus (Ch4). The cognitive domains performance was measured using the Montreal Cognitive Assessment (MoCA). Additionally, we evaluated the diagnostic value of free water fraction (FWf) within the cholinergic system.
FWf in the bilateral Ch1-3 and Ch4 regions increased with age, and was significantly higher in aMCI and AD ( < 0.001). In AD, the FWf within Ch4 was correlated with total MoCA score ( = -0.42, = 0.015), especially with visual spatial/executive ( = -0.47, = 0.006) and orientation deficits ( = -0.38, = 0.029). No significant correlations were found in the aMCI group. ROC curve analysis showed that FWf within the cholinergic brain network had high diagnostic efficacy for AD versus HC (AUC = 0.958, 95% CI = 0.909-1.00), and moderate diagnostic efficacy for aMCI versus HC (AUC = 0.795, 95% CI = 0.685-0.905) and aMCI versus AD (AUC = 0.719, 95% CI = 0.589-0.850).
FW imaging captures microstructural damage in the cholinergic brain network across the entire AD continuum. These changes occur early in aMCI but selectively affect domain-specific cognition in the later stages of AD, possibly through cholinergic network dysfunction. Our results highlight the potential of free water imaging as a biomarker for cognitive decline.
细胞外自由水（FW）增加被认为比传统扩散张量成像（DTI）指标能提供更好的病理生理信息。胆碱能脑网络是认知功能的关键枢纽，该系统中自由水成像检测到的微观结构变化可能与阿尔茨海默病（AD）的认知障碍有关。然而，胆碱能脑网络中FW变化对整个AD连续体认知领域的具体影响及其诊断价值仍不清楚。
在此，我们基于自由水校正扩散张量成像研究了健康对照者（n = 36）、遗忘型轻度认知障碍（aMCI；n = 31）、AD组（n = 33）的基底前脑胆碱能自由水改变。胆碱能基底前脑亚区分为布罗卡斜角带（Ch1 - 3）和迈内特基底核（Ch4）。使用蒙特利尔认知评估（MoCA）测量认知领域表现。此外，我们评估了胆碱能系统内自由水分数（FWf）的诊断价值。
双侧Ch1 - 3和Ch4区域的FWf随年龄增加，在aMCI和AD中显著更高（P < 0.001）。在AD中，Ch4内的FWf与MoCA总分相关（r = -0.42，P = 0.015），尤其与视觉空间/执行功能（r = -0.47，P = 0.006）和定向障碍（r = -0.38，P = 0.029）相关。在aMCI组中未发现显著相关性。受试者工作特征曲线分析表明，胆碱能脑网络内的FWf对AD与健康对照（HC）具有高诊断效能（AUC = 0.958，95% CI = 0.909 - 1.00），对aMCI与HC具有中等诊断效能（AUC = 0.795，95% CI = 0.685 - 0.905），对aMCI与AD具有中等诊断效能（AUC = 0.719，95% CI = 0.589 - 0.850）。
FW成像捕捉了整个AD连续体中胆碱能脑网络的微观结构损伤。这些变化在aMCI早期出现，但在AD后期选择性地影响特定领域的认知，可能是通过胆碱能网络功能障碍。我们的结果突出了自由水成像作为认知衰退生物标志物的潜力。
