Placental growth factor as a sensitive biomarker for vascular cognitive impairment
Jason D. Hinman, Fanny M. Elahi, Davis S. Chong, Hannah L. Radabaugh, Adam R. Ferguson, Pauline Maillard, Jeffrey F. Thompson, Gary A. Rosenberg, Abhay P. Sagare, Abhay Moghekar, Hanzhang Lu, Tiffany Lee, Donna M. Wilcock, Claudia L. Satizábal, Russell P. Tracy, Sudha Seshadri, Kristin Schwab, Karl G. Helmer, Herpreet Singh, Pia Kivisäkk, S Greenberg, Charlie S. DeCarli, Joel H. Kramer
Abstract
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.