Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, USA.
Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
Tissue Barriers. 2022 Jan 2;10(1):1963143. doi: 10.1080/21688370.2021.1963143. Epub 2021 Sep 18.
Metabolic deficits at brain-fluid barriers are an increasingly recognized feature of cognitive decline in older adults. At the blood-cerebrospinal fluid barrier, water is transported across the choroid plexus (CP) epithelium against large osmotic gradients via processes tightly coupled to activity of the sodium/potassium pump. Here, we quantify CP homeostatic water exchange using dynamic contrast-enhanced MRI and investigate the association of the water efflux rate constant (k) with cognitive dysfunction in older individuals. Temporal changes in the longitudinal relaxation rate constant (R) after contrast agent bolus injection were measured in a CP region of interest in 11 participants with mild cognitive dysfunction [CI; 73 ± 6 years] and 28 healthy controls [CN; 72 ± 7 years]. k was determined from a modified two-site pharmacokinetic exchange analysis of the R time-course. K, a measure of contrast agent extravasation to the interstitial space was also determined. Cognitive function was assessed by neuropsychological test performance. k averages 5.8 ± 2.7 s in CN individuals and is reduced by 2.4 s [. 40%] in CI subjects. Significant associations of k with global cognition and multiple cognitive domains are observed. K averages 0.13 ± 0.07 min and declines with age [-0.006 ± 0.002 min yr], but shows no difference between CI and CN individuals or association with cognitive performance. Our findings suggest that the CP water efflux rate constant is associated with cognitive dysfunction and shows an age-related decline in later life, consistent with the metabolic disturbances that characterize brain aging.
脑-脑脊液屏障的代谢缺陷是老年人认知能力下降的一个日益被认识到的特征。在血-脑脊髓液屏障中，水通过与钠/钾泵活性紧密偶联的过程，逆着大的渗透梯度穿过脉络丛（CP）上皮转运。在这里，我们使用动态对比增强 MRI 定量 CP 的水交换，并研究水流出率常数（k）与老年人认知功能障碍的相关性。在 11 名轻度认知功能障碍患者（CI；73 ± 6 岁）和 28 名健康对照者（CN；72 ± 7 岁）的 CP 感兴趣区中测量了对比剂团注后纵向弛豫率常数（R）的时间变化。从 R 时间过程的改进的双位点药代动力学交换分析确定 k。还确定了 k，这是衡量对比剂向间质空间外渗的指标。认知功能通过神经心理学测试表现来评估。CN 个体的 k 平均值为 5.8 ± 2.7 s，CI 受试者的 k 降低了 2.4 s [40%]。观察到 k 与总体认知和多个认知领域显著相关。k 的平均值为 0.13 ± 0.07 min，随年龄增长而下降[-0.006 ± 0.002 min yr]，但在 CI 和 CN 个体之间没有差异，也与认知表现无关。我们的研究结果表明，CP 的水流出率常数与认知功能障碍有关，并显示出与大脑衰老相关的生命后期的年龄相关性下降，这与代谢紊乱一致，这些代谢紊乱是大脑衰老的特征。
