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.
|Journal||Alzheimer's and Dementia|
|State||Accepted/In press - 2023|
Bibliographical noteFunding Information:
The authors would like to thank all the members of the MarkVCID consortium including those serving on the Fluid Biomarker Subcommittee. MarkVCID is supported by the National Institutes of Health (grant numbers: U24NS100591, UH2NS100599, UH2/UH3NS100605, UH2NS100588, UH2NS100608, UH2NS100606, UH2NS100598, UH2NS100614, UF1NS125513). Drs. Satizabal and Seshadri are partly supported by P30 AG066546. Dr. Seshadri is also supported by the Bill and Rebecca Reed Endowment for Precision Therapies and Palliative Care and by an endowment from the Barker Foundation.
© 2023 the Alzheimer's Association.
- placental growth factor
- vascular cognitive impairment
ASJC Scopus subject areas
- Health Policy
- Developmental Neuroscience
- Clinical Neurology
- Geriatrics and Gerontology
- Cellular and Molecular Neuroscience
- Psychiatry and Mental health