Abstract
INTRODUCTION
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.
METHODS
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).
RESULTS
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.
DISCUSSION
Elevated PlGF may contribute to WMH and cognitive impairment through white matter FW accumulation.
CLINICAL TRIAL REGISTRATION
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.
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This post is Copyright: Kyle C. Kern,
Manu Vohra,
Marissa L. Thirion,
Danny J. J. Wang,
Donna M. Wilcock,
Jeffrey F. Thompson,
Gary A. Rosenberg,
Abhay Sagare,
Abhay Moghekar,
Hanzhang Lu,
Tiffany Lee,
Fanny M. Elahi,
Claudia L. Satizabal,
Russell Tracy,
Sudha Seshadri,
Kristin Schwab,
Karl Helmer,
Herpreet Singh,
Pia Kivisäkk,
Steven M. Greenberg,
Keith Vossel,
Joel H. Kramer,
Pauline Maillard,
Charles S. DeCarli,
Jason D. Hinman | December 18, 2024