Placental growth factor as a sensitive biomarker for vascular cognitive impairment

Jason D. Hinman, Fanny Elahi, Davis Chong, Hannah Radabaugh, Adam Ferguson, Pauline Maillard, Jeffrey F. Thompson, Gary A. Rosenberg, Abhay Sagare, Abhay Moghekar, Hanzhang Lu, Tiffany Lee, Donna Wilcock, Claudia L. Satizabal, Russell Tracy, Sudha Seshadri, Kristin Schwab, Karl Helmer, Herpreet Singh, Pia KivisäkkSteve Greenberg, Charlie DeCarli, Joel Kramer

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


INTRODUCTION: High-performing biomarkers measuring the vascular contributions to cognitive impairment and dementia are lacking. METHODS: Using a multi-site observational cohort study design, we examined the diagnostic accuracy of plasma placental growth factor (PlGF) within the MarkVCID Consortium (n = 335; CDR 0-1). Subjects underwent clinical evaluation, cognitive testing, MRI, and blood sampling as defined by Consortium protocols. RESULTS: In the prospective population of 335 subjects (72.2 ± 7.8 years of age, 49.3% female), plasma PlGF (pg/mL) shows an ordinal odds ratio (OR) of 1.16 (1.07-1.25; P =.0003) for increasing Fazekas score and ordinal OR of 1.22 (1.14-1.32; P <.0001) for functional cognitive impairment measured by the Clinical Dementia Rating scale. We achieved the primary study outcome of a site-independent association of plasma PlGF (pg/mL) with white matter injury and cognitive impairment in two of three study cohorts. Secondary outcomes using the full MarkVCID cohort demonstrated that plasma PlGF can significantly discriminate individuals with Fazekas ≥ 2 and CDR = 0.5 (area under the curve [AUC] = 0.74) and CDR = 1 (AUC = 0.89) from individuals with CDR = 0. DISCUSSION: Plasma PlGF measured by standardized immunoassay functions as a stable, reliable, diagnostic biomarker for cognitive impairment associated with substantial white matter burden.

Original languageEnglish
Pages (from-to)3519-3527
Number of pages9
JournalAlzheimer's and Dementia
Issue number8
StatePublished - Aug 2023

Bibliographical note

Publisher Copyright:
© 2023 the Alzheimer's Association.


  • biomarker
  • diagnosis
  • placental growth factor
  • vascular cognitive impairment

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health


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