Cogswell Petrice M, Weigand Stephen D, Wiste Heather J, Gunter Jeffrey L, Graff-Radford Jonathan, Jones David T, Schwarz Christopher G, Senjem Matthew L, Knopman David S, Petersen Ronald C, Jack Clifford R
Department of Radiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Department of Health Sciences Research, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Neuroimage. 2021 May 15;232:117899. doi: 10.1016/j.neuroimage.2021.117899. Epub 2021 Feb 23.
Disproportionately enlarged subarachnoid-space hydrocephalus (DESH), characterized by tight high convexity CSF spaces, ventriculomegaly, and enlarged Sylvian fissures, is thought to be an indirect marker of a CSF dynamics disorder. The clinical significance of DESH with regard to cognitive decline in a community setting is not yet well defined. The goal of this work is to determine if DESH is associated with cognitive decline. Participants in the population-based Mayo Clinic Study of Aging (MCSA) who met the following criteria were included: age ≥ 65 years, 3T MRI, and diagnosis of cognitively unimpaired or mild cognitive impairment at enrollment as well as at least one follow-up visit with cognitive testing. A support vector machine based method to detect the DESH imaging features on T1-weighted MRI was used to calculate a "DESH score", with positive scores indicating a more DESH-like imaging pattern. For the participants who were cognitively unimpaired at enrollment, a Cox proportional hazards model was fit with time defined as years from enrollment to first diagnosis of mild cognitive impairment or dementia, or as years to last known cognitively unimpaired diagnosis for those who did not progress. Linear mixed effects models were fit among all participants to estimate annual change in cognitive z scores for each domain (memory, attention, language, and visuospatial) and a global z score. For all models, covariates included age, sex, education, APOE genotype, cortical thickness, white matter hyperintensity volume, and total intracranial volume. The hazard of progression to cognitive impairment was an estimated 12% greater for a DESH score of +1 versus -1 (HR 1.12, 95% CI 0.97-1.31, p = 0.11). Global and attention cognition declined 0.015 (95% CI 0.005-0.025) and 0.016 (95% CI 0.005-0.028) z/year more, respectively, for a DESH score of +1 vs -1 (p = 0.01 and p = 0.02), with similar, though not statistically significant DESH effects in the other cognitive domains. Imaging features of disordered CSF dynamics are an independent predictor of subsequent cognitive decline in the MCSA, among other well-known factors including age, cortical thickness, and APOE status. Therefore, since DESH contributes to cognitive decline and is present in the general population, identifying individuals with DESH features may be important clinically as well as for selection in clinical trials.
蛛网膜下腔不成比例扩大性脑积水（DESH）的特征为高凸部脑脊液间隙狭窄、脑室扩大和大脑外侧裂增宽，被认为是脑脊液动力学障碍的间接标志物。在社区环境中，DESH与认知功能下降的临床意义尚未明确界定。这项研究的目的是确定DESH是否与认知功能下降有关。纳入了基于人群的梅奥诊所衰老研究（MCSA）中符合以下标准的参与者：年龄≥65岁、接受3T磁共振成像（MRI）检查，且在入组时以及至少一次随访认知测试时被诊断为认知功能未受损或轻度认知障碍。使用基于支持向量机的方法来检测T1加权MRI上的DESH成像特征，以计算“DESH评分”，阳性评分表明更类似DESH的成像模式。对于入组时认知功能未受损的参与者，采用Cox比例风险模型，将时间定义为从入组到首次诊断为轻度认知障碍或痴呆的年数，或对于未进展者定义为到最后已知认知功能未受损诊断的年数。在所有参与者中拟合线性混合效应模型，以估计每个领域（记忆、注意力、语言和视觉空间）以及总体z评分的认知z评分的年度变化。对于所有模型，协变量包括年龄、性别、教育程度、载脂蛋白E（APOE）基因型、皮质厚度、白质高信号体积和总颅内体积。DESH评分为+1与-1相比，进展为认知障碍的风险估计高12%（风险比1.12，95%置信区间0.97 - 1.31，p = 0.11）。DESH评分为+1与-1相比，总体和注意力认知每年分别多下降0.015（95%置信区间0.005 - 0.025）和0.016（95%置信区间0.005 - 0.028）z评分（p = 0.01和p = 0.02），在其他认知领域DESH效应相似但无统计学意义。除了年龄、皮质厚度和APOE状态等其他众所周知的因素外，脑脊液动力学紊乱的成像特征是MCSA中后续认知功能下降的独立预测因素。因此，由于DESH会导致认知功能下降且存在于普通人群中，识别具有DESH特征的个体在临床上以及临床试验选择中可能都很重要。
