Placental growth factor as a sensitive biomarker for vascular cognitive impairment.

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.

Temporal Patterning of Neurofilament Light as a Blood-Based Biomarker for Stroke: A Systematic Review and Meta-Analysis.

Damage to axons is a core feature of ischemic stroke and cerebrovascular disease. The burden of axonal injury is correlated with the acute clinical deficits, the underlying burden of ischemic brain injury, the prognosis of recovery, and may be a meaningful therapeutic target for brain repair. Neurofilament light chain (NfL) has been identified as a blood-based biomarker that reflects neuroaxonal damage resulting from stroke. However, the utility of NfL as a blood-based biomarker in stroke is confounded by studies examining different temporal windows and patient populations. We conducted a systematic review and meta-analysis to verify the utility of blood NfL as a diagnostic, prognostic, and monitoring stroke biomarker. Nineteen studies reporting serum/plasma NfL values for a total of 4,237 distinct patients with stroke were identified. Using available summary data from the 10 studies that employed a common immunoassay platform, we utilized random effects linear mixed modeling and weighted averages to create a phasic model of serum/plasma NfL values in distinct time periods of acute stroke. Weighted averages show that blood NfL levels vary significantly across three distinct temporal epochs of acute (0-7 days), subacute (9-90 days), and chronic (>90 days) stroke with a steep peak in the early subacute period between 14 and 21 days after stroke. Blood NfL values can function as a diagnostic biomarker in distinguishing acute ischemic stroke from transient ischemic attack as well as amongst other cerebrovascular subtypes. Release of NfL into the bloodstream after stroke follows a distinct temporal dynamic that lags several weeks behind stroke onset and reliably associates with a stroke diagnosis despite some variability based on stroke subtype and severity. Identification of these temporal dynamics and the contribution of co- existent cerebrovascular disease states can improve the value of NfL as a stroke biomarker.