Lee Woo-Jin, Jung Keun-Hwa, Ryu Young Jin, Kim Jeong-Min, Lee Soon-Tae, Chu Kon, Kim Manho, Lee Sang Kun, Roh Jae-Kyu
Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.
PLoS One. 2017 Sep 14;12(9):e0184999. doi: 10.1371/journal.pone.0184999. eCollection 2017.
Cerebral white matter hyperintensities (WMHs) are central MRI markers of the brain aging process, but the mechanisms for its progression remain unclear. In this study, we aimed to determine whether the baseline serum cystatin C level represented one mechanism underlying WMH progression, and whether it was associated with the long-term progression of cerebral WMH volume in MRI. 166 consecutive individuals who were ≥50 years of age and who underwent initial/follow-up MRI evaluations within an interval of 34-45 months were included. Serum cystatin C level, glomerular-filtration rate (GFR), and other laboratory parameters were measured at their initial evaluation and at the end of follow-up. Cerebrovascular risk factors, medications, and blood-pressure parameters were also reviewed. WMH progression rate was measured by subtracting WMH volume at baseline from that at the follow-up using volumetric analysis, divided by the MRI intervals. At baseline, WMH volume was 9.61±13.17 mL, mean GFR was 77.3±22.8 mL/min, and mean cystatin C level was 0.92±0.52 mg/L. After 37.9±3.4 months, the change in WMH volume was 3.64±6.85 mL, the progression rate of WMH volume was 1.18±2.28 mL/year, the mean ΔGFR was 2.4±7.9 mL/min, and the mean Δcystatin C was 0.03±0.34 mg/L. The progression rate of WMH volume was linearly associated with cystatin C level (B coefficient = 0.856; 95% confidence interval [CI] 0.174-1.538; P = 0.014), along with the baseline WMH volume (B = 0.039; 95% CI 0.019-0.059; P<0.001), after adjusting for the conventional vascular risk factors, laboratory parameters, medication profiles, and GFR. Especially, patients with a baseline level of cystatin C ≥1.00 mg/L exhibited a much higher progression rate of WMH as compared with those with a baseline level of cystatin C <1.00 mg/L (1.60±1.91 mL/year vs. 0.82±1.63 mL/year, P = 0.010). We concluded that serum cystatin C level is independently associated with the long-term progression rate of the cerebral WMH volume. Therefore, serum cystatin C level might predict the progression of cerebral WMH.
脑白质高信号（WMHs）是脑老化过程的核心磁共振成像（MRI）标志物，但其进展机制仍不清楚。在本研究中，我们旨在确定基线血清胱抑素C水平是否代表WMH进展的一种潜在机制，以及它是否与MRI中脑WMH体积的长期进展相关。纳入了166名年龄≥50岁且在34 - 45个月间隔内接受初次/随访MRI评估的连续个体。在初次评估和随访结束时测量血清胱抑素C水平、肾小球滤过率（GFR）及其他实验室参数。还回顾了脑血管危险因素、用药情况和血压参数。使用容积分析通过从随访时的WMH体积中减去基线时的WMH体积，再除以MRI间隔时间来测量WMH进展率。基线时，WMH体积为9.61±13.17 mL，平均GFR为77.3±22.8 mL/min，平均胱抑素C水平为0.92±0.52 mg/L。37.9±3.4个月后，WMH体积变化为3.64±6.85 mL，WMH体积进展率为1.18±2.28 mL/年，平均ΔGFR为2.4±7.9 mL/min，平均Δ胱抑素C为0.03±0.34 mg/L。在调整了传统血管危险因素、实验室参数、用药情况和GFR后，WMH体积进展率与胱抑素C水平呈线性相关（B系数 = 0.856；95%置信区间[CI] 0.174 - 1.538；P = 0.014），同时与基线WMH体积相关（B = 0.039；95% CI 0.019 - 0.059；P<0.001）。特别是，基线胱抑素C水平≥1.00 mg/L的患者与基线胱抑素C水平<1.00 mg/L的患者相比，WMH进展率要高得多（1.60±1.91 mL/年对0.82±1.63 mL/年，P = 0.010）。我们得出结论，血清胱抑素C水平与脑WMH体积的长期进展率独立相关。因此，血清胱抑素C水平可能预测脑WMH的进展。
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