From the Imaging of Dementia and Aging Laboratory and Center for Neurosciences (P.M., E.F., B.S., O.M., C.D.), Davis, CA; and Department of Neurology (D.K.J., J.M.O., S.T.F., C.D.), University of California, Davis.
Neurology. 2019 May 7;92(19):e2221-e2231. doi: 10.1212/WNL.0000000000007449. Epub 2019 Apr 5.
To determine whether free water (FW) content, initially developed to correct metrics derived from diffusion tensor imaging and recently found to be strongly associated with vascular risk factors, may constitute a sensitive biomarker of white matter (WM) microstructural differences associated with cognitive performance but remains unknown.
Five hundred thirty-six cognitively diverse individuals, aged 77 ± 8 years, received yearly comprehensive clinical evaluations and a baseline MRI examination of whom 224 underwent follow-up MRI. WM microstructural measures, including FW, fractional anisotropy, and mean diffusivity corrected for FW and WM hyperintensity burden were computed within WM voxels of each individual. Baseline and change in MRI metrics were then used as independent variables to explain baseline and change in episodic memory (EM), executive function (EF), and Clinical Dementia Rating (CDR) scores using linear, logistic, and Cox proportional-hazards regressions.
Higher baseline FW and WM hyperintensity were associated with lower baseline EM and EF, higher baseline CDR, accelerated EF and EM decline, and higher probability to transition to a more severe CDR stage ( values <0.01). Annual change in FW was also found to be associated with concomitant change in cognitive and functional performance ( values <0.01).
This study finds cross-sectional and longitudinal associations between FW content and trajectory of cognitive and functional performance in a large sample of cognitively diverse individuals. It supports the need to investigate the pathophysiologic process that manifests increased FW, potentially leading to more severe WM territory injury and promoting cognitive and functional decline.
确定游离水（FW）含量是否可以作为一种与认知表现相关的白质（WM）微观结构差异的敏感生物标志物，FW 最初是为了校正扩散张量成像衍生的指标而开发的，最近发现它与血管危险因素密切相关，但这一点尚未可知。
536 名认知能力不同的个体，年龄 77±8 岁，每年接受全面的临床评估和基线 MRI 检查，其中 224 名进行了随访 MRI。在每个个体的 WM 体素内计算 WM 微观结构测量值，包括 FW、各向异性分数和校正 FW 和 WM 高信号负荷的平均弥散度。然后，将基线和 MRI 指标的变化作为自变量，使用线性、逻辑和 Cox 比例风险回归来解释基线和情节记忆（EM）、执行功能（EF）和临床痴呆评定量表（CDR）评分的变化。
较高的基线 FW 和 WM 高信号与较低的基线 EM 和 EF、较高的基线 CDR、EF 和 EM 衰退加速以及向更严重的 CDR 阶段转变的可能性增加（P 值<0.01）相关。FW 的年度变化也与认知和功能表现的同时变化相关（P 值<0.01）。
这项研究在一个认知能力多样化的大样本中发现了 FW 含量与认知和功能表现的横断面和纵向关联。它支持需要研究表现出 FW 增加的病理生理过程，这可能导致更严重的 WM 区域损伤，并促进认知和功能下降。
