Barisano Giuseppe, Iv Michael, Choupan Jeiran, Hayden-Gephart Melanie
Department of Neurosurgery, Stanford University, Stanford, CA, USA.
Department of Radiology, Stanford University, Stanford, CA, USA.
EBioMedicine. 2025 Jan;111:105523. doi: 10.1016/j.ebiom.2024.105523. Epub 2024 Dec 24.
Perivascular spaces (PVS) on brain MRI are surrogates for small parenchymal blood vessels and their perivascular compartment, and may relate to brain health. However, it is unknown whether PVS can predict dementia risk and brain atrophy trajectories in participants without dementia, as longitudinal studies on PVS are scarce and current methods for PVS assessment lack robustness and inter-scanner reproducibility.
We developed a robust algorithm to automatically assess PVS count and size on clinical MRI, and investigated 1) their relationship with dementia risk and brain atrophy in participants without dementia, 2) their longitudinal evolution, and 3) their potential use as a screening tool in simulated clinical trials. We analysed 46,478 clinical measurements of cognitive functioning and 20,845 brain MRI scans from 10,004 participants (71.1 ± 9.7 years-old, 56.6% women) from three publicly available observational studies on ageing and dementia (the Alzheimer's Disease Neuroimaging Initiative, the National Alzheimer's Coordinating Centre database, and the Open Access Series of Imaging Studies). Clinical and MRI data collected between 2004 and 2022 were analysed with consistent methods, controlling for confounding factors, and combined using mixed-effects models.
Our fully-automated method for PVS assessment showed excellent inter-scanner reproducibility (intraclass correlation coefficients >0.8). Fewer PVS and larger PVS diameter at baseline predicted higher dementia risk and accelerated brain atrophy. Longitudinal trajectories of PVS markers differed significantly in participants without dementia who converted to dementia compared with non-converters. In simulated placebo-controlled trials for treatments targeting cognitive decline, screening out participants at low risk of dementia based on our PVS markers enhanced the power of the trial independently of Alzheimer's disease biomarkers.
These robust cerebrovascular markers predict dementia risk and brain atrophy and may improve risk-stratification of patients, potentially reducing cost and increasing throughput of clinical trials to combat dementia.
US National Institutes of Health.
脑磁共振成像（MRI）上的血管周围间隙（PVS）是脑实质小血管及其血管周围腔隙的替代指标，可能与脑健康有关。然而，由于关于PVS的纵向研究稀缺，且目前PVS评估方法缺乏稳健性和不同扫描仪间的可重复性，因此尚不清楚PVS能否预测无痴呆症参与者的痴呆风险和脑萎缩轨迹。
我们开发了一种稳健的算法，用于在临床MRI上自动评估PVS数量和大小，并研究了：1）它们与无痴呆症参与者的痴呆风险和脑萎缩的关系；2）它们的纵向演变；3）它们在模拟临床试验中作为筛查工具的潜在用途。我们分析了来自三项关于衰老和痴呆症的公开可用观察性研究（阿尔茨海默病神经影像倡议、国家阿尔茨海默病协调中心数据库和开放获取影像研究系列）的10,004名参与者（71.1±9.7岁，56.6%为女性）的46,478项认知功能临床测量数据和20,845次脑MRI扫描数据。使用一致的方法分析了2004年至2022年期间收集的临床和MRI数据，控制混杂因素，并使用混合效应模型进行合并。
我们用于PVS评估的全自动方法显示出优异的不同扫描仪间可重复性（组内相关系数>0.8）。基线时较少的PVS数量和较大的PVS直径预测了更高的痴呆风险和更快的脑萎缩。与未转化为痴呆症的参与者相比，转化为痴呆症的无痴呆症参与者的PVS标志物纵向轨迹有显著差异。在针对认知衰退的模拟安慰剂对照试验中，基于我们的PVS标志物筛选出痴呆风险低的参与者，可独立于阿尔茨海默病生物标志物提高试验效能。
这些稳健的脑血管标志物可预测痴呆风险和脑萎缩，并可能改善患者的风险分层，潜在地降低成本并提高对抗痴呆症临床试验的通量。
美国国立卫生研究院
