Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Memory Aging and Cognition Centre, Department of Pharmacology, Yong Loo Lim School of Medicine, National University of Singapore, Singapore.
J Neurol Neurosurg Psychiatry. 2022 Jan;93(1):14-23. doi: 10.1136/jnnp-2021-326571. Epub 2021 Sep 11.
It has been suggested that diffusion tensor imaging (DTI) measures sensitive to white matter (WM) damage may predict future dementia risk not only in cerebral small vessel disease (SVD), but also in mild cognitive impairment. To determine whether DTI measures were associated with cognition cross-sectionally and predicted future dementia risk across the full range of SVD severity, we established the International OPtimising mulTImodal MRI markers for use as surrogate markers in trials of Vascular Cognitive Impairment due to cerebrAl small vesseL disease collaboration which included six cohorts.
Among the six cohorts, prospective data with dementia incidences were available for three cohorts. The associations between six different DTI measures and cognition or dementia conversion were tested. The additional contribution to prediction of other MRI markers of SVD was also determined.
The DTI measure mean diffusivity (MD) median correlated with cognition in all cohorts, demonstrating the contribution of WM damage to cognition. Adding MD median significantly improved the model fit compared to the clinical risk model alone and further increased in all single-centre SVD cohorts when adding conventional MRI measures. Baseline MD median predicted dementia conversion. In a study with severe SVD (SCANS) change in MD median also predicted dementia conversion. The area under the curve was best when employing a multimodal MRI model using both DTI measures and other MRI measures.
Our results support a central role for WM alterations in dementia pathogenesis in all cohorts. DTI measures such as MD median may be a useful clinical risk predictor. The contribution of other MRI markers varied according to disease severity.
有研究表明,弥散张量成像(DTI)测量对白质(WM)损伤敏感的指标不仅可以预测脑小血管病(SVD)患者的未来痴呆风险,也可以预测轻度认知障碍患者的未来痴呆风险。为了确定 DTI 测量指标是否与认知功能有关,并预测整个 SVD 严重程度范围内的未来痴呆风险,我们成立了国际优化多模态 MRI 标志物用于脑小血管病导致血管性认知障碍试验的替代标志物研究协作组,其中包含六个队列。
在这六个队列中,有三个队列具有前瞻性的痴呆发病率数据。测试了 6 种不同的 DTI 测量指标与认知功能或痴呆转化之间的相关性。还确定了它们对 SVD 其他 MRI 标志物预测的额外贡献。
所有队列的 DTI 测量指标平均弥散度(MD)中位数与认知功能相关,证明 WM 损伤对认知功能有影响。与单独的临床风险模型相比,MD 中位数的加入显著提高了模型拟合度,并且在加入常规 MRI 测量时,所有单中心 SVD 队列的模型拟合度都进一步提高。基线 MD 中位数可以预测痴呆转化。在 SVD 严重程度较高的研究(SCANS)中,MD 中位数的变化也可以预测痴呆转化。当使用包括 DTI 测量指标和其他 MRI 测量指标的多模态 MRI 模型时,曲线下面积最佳。
我们的研究结果支持 WM 改变在所有队列的痴呆发病机制中起核心作用。MD 中位数等 DTI 测量指标可能是一种有用的临床风险预测指标。其他 MRI 标志物的贡献因疾病严重程度而异。