Kern Kyle C, Vohra Manu, Thirion Marissa L, Wang Danny J J, Wilcock Donna M, Thompson Jeffrey F, Rosenberg Gary A, Sagare Abhay, Moghekar Abhay, Lu Hanzhang, Lee Tiffany, Elahi Fanny M, Satizabal Claudia L, Tracy Russell, Seshadri Sudha, Schwab Kristin, Helmer Karl, Singh Herpreet, Kivisäkk Pia, Greenberg Steven M, Vossel Keith, Kramer Joel H, Maillard Pauline, DeCarli Charles S, Hinman Jason D
Department of Neurology, University of California Los Angeles, Los Angeles, California, USA.
Department of Neurology, West Los Angeles Veterans Affairs Medical Center, Los Angeles, California, USA.
Alzheimers Dement. 2025 Feb;21(2):e14408. doi: 10.1002/alz.14408. Epub 2024 Dec 18.
Placental growth factor (PlGF) may regulate cerebrovascular permeability. We hypothesized that white matter interstitial fluid accumulation, estimated via magnetic resonance imaging (MRI) free water (FW), would explain the associations between elevated PlGF, white matter hyperintensities (WMH), and cognitive impairment.
MarkVCID consortium participants ≥55 years old with plasma PlGF and brain MRI were included. We tested cross-sectionally whether FW mediated the associations between PlGF and WMH, or PlGF and cognition, measured using the Clinical Dementia Rating (CDR) scale and an executive function (EF) composite (Uniform Data Set version 3 [UDS3]-EF).
For 370 participants (mean age 72), a higher PlGF was associated with higher FW, higher WMH, and higher CDR, but not UDS3-EF. Higher FW was associated with higher WMH, higher CDR, and lower UDS3-EF. FW explained 26% of the association between PlGF and CDR and 73% of the association between PlGF and WMH.
Elevated PlGF may contribute to WMH and cognitive impairment through white matter FW accumulation.
NCT06284213 HIGHLIGHTS: PlGF is a promising blood-based biomarker for vascular cognitive impairment. In MarkVCID, higher PlGF was associated with accumulated white matter FW on MRI. FW mediated the association between higher PlGF and MRI-visible white matter injury. FW mediated the association between PlGF and worse CDR scale. PlGF may contribute to cognitive dysfunction via accumulated interstitial fluid.
胎盘生长因子（PlGF）可能调节脑血管通透性。我们假设，通过磁共振成像（MRI）自由水（FW）估计的白质间质液积聚可以解释PlGF升高、白质高信号（WMH）和认知障碍之间的关联。
纳入年龄≥55岁、有血浆PlGF和脑部MRI检查结果的MarkVCID联盟参与者。我们进行横断面测试，以检验FW是否介导了PlGF与WMH之间，或PlGF与认知之间的关联，认知采用临床痴呆评定量表（CDR）和执行功能（EF）综合评分（统一数据集版本3 [UDS3]-EF）进行测量。
对于370名参与者（平均年龄72岁），较高的PlGF与较高的FW、较高的WMH和较高的CDR相关，但与UDS3-EF无关。较高的FW与较高的WMH、较高的CDR和较低的UDS3-EF相关。FW解释了PlGF与CDR之间26%的关联以及PlGF与WMH之间73%的关联。
PlGF升高可能通过白质FW积聚导致WMH和认知障碍。
NCT06284213 要点：PlGF是一种有前景的基于血液的血管性认知障碍生物标志物。在MarkVCID研究中，较高的PlGF与MRI上白质FW积聚相关。FW介导了较高的PlGF与MRI可见的白质损伤之间的关联。FW介导了PlGF与较差的CDR量表评分之间的关联。PlGF可能通过间质液积聚导致认知功能障碍。
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