A novel composite biomarker score for the identification of cognitive impairment in patients with heart failure: a...

Among 6.7 million Americans with heart failure (HF), 40%-60% are estimated to have mild cognitive impairment (MCI) and are at-risk for vascular contributions to cognitive impairment and dementia (VCID). This pilot study examined whether neurodegenerative and inflammatory serum biomarkers are elevated in HF and whether a combination of these biomarkers predicts cognitive performance.

Thirty-four HF patients (mean age = 69 years, 62% male) were recruited from Banner-University cardiology clinics and underwent blood sampling and neuropsychological testing to derive an 'Actual Composite Cognitive Score.' Age-matched healthy controls included (i) 11 individuals (mean age = 63 years, 20% male) who completed identical procedures and (ii) 24 individuals used exclusively for biomarker analysis. Biomarkers-serum neurofilament light chain (NfL), plasma phosphorylated tau (pTau181, pTau217), placental growth factor (PlGF), cytokines, and NT-proBNP-were quantified using Quanterix Simoa, Milliplex, and Elecsys (Roche) assays.

HF participants scored worse in cognitive assessments than controls (p = 0.0001). Serum NfL (p = 0.02), IL-6 (p < 0.0001), IL-12p40 (p < 0.0001), IL-15 (p = 0.005), MIP-1α (p = 0.007), TNFβ (p = 0.03), and TNFα (p = 0.0002) were increased in HF. NfL and pTau181 correlated with NT-proBNP; NfL, IL-6, and TNFα inversely correlated with cognitive scores. The Composite Biomarker Cognitive Score = NfL + NT-proBNP + IL-6 + TNFα negatively correlated with the Actual Composite Cognitive Score (r = -0.60, p = 0.0002).

These results establish a Composite Biomarker Cognitive Score, which is predictive of cognitive impairment in HF, and may aid in identifying HF patients suitable for cognitive-protective therapies.