Longitudinal trajectories of neurodegenerative biomarkers in the blood of patients with chronic heart failure

Abstract

Abstract Introduction Chronic heart failure (HF) is associated with mild cognitive impairment (MCI), vascular dementia, and Alzheimer’s disease. Blood-based neurodegenerative biomarkers may support early risk stratification and outcome prediction in HF. Methods In the prospective Cognition.Matters-HF cohort study, serum neurofilament light chain (NfL), glial fibrillary acidic protein, and phosphorylated tau protein-181, as well as plasma amyloid-β peptides (Aβ38, Aβ40, Aβ42) and β-synuclein, were quantified longitudinally over 36 months using ultrasensitive immunoassays and immunoprecipitation mass spectrometry. Cerebral magnetic resonance imaging and standardized domain-specific cognitive testing were performed. Multivariable logistic regression was used to assess associations with future MCI, brain structural changes, and 5-year all-cause mortality. Results Among 104 patients with chronic HF (10% female, age 64 ± 10 years), all biomarkers except NfL increased significantly over 3 years (P < .05). Median annual percentage changes were 36.6% for phosphorylated tau protein-181, 4.6% for glial fibrillary acidic protein, 2.6% for β-synuclein, 0.6% for Aβ38, 0.5% for Aβ40, and 0.3% for Aβ42. After adjusting for clinical confounders, increases in Aβ38 and Aβ42 independently associated with future MCI, pathological white matter hyperintensity progression (>5% per year), and 5-year mortality (all P < .05). Glial fibrillary acidic protein levels and phosphorylated tau protein-181 trajectories were independently associated with pathological brain atrophy (>0.3% per year). Conclusion In clinically stable patients with chronic HF, longitudinal increases in circulating amyloid-β peptides associated with cognitive decline, structural brain changes, and mortality. Serial biomarker assessment provided stronger prognostic information than baseline measurements alone. Replication in larger cohorts is required.