https://doi.org/10.1007/s00392-024-02526-y
1Universitätsklinikum Würzburg Medizinische Klinik und Poliklinik I, ZIM Kardiologie Würzburg, Deutschland; 2Universitätsklinikum Würzburg Deutsches Zentrum für Herzinsuffizienz Würzburg, Deutschland; 3Universitätsklinikum Würzburg Medizinische Klinik I, Kardiologie Würzburg, Deutschland; 4Universitätsklinikum Würzburg Medizinische Klinik und Poliklinik I Würzburg, Deutschland; 5Universitätsklinikum Halle (Saale) Halle (Saale), Deutschland; 6Universitätsklinikum Ulm Ulm, Deutschland
Background and aims: Chronic heart failure (HF) predisposes to mild cognitive impairment (MCI), vascular dementia, and Alzheimer’s disease. However, underlying pathophysiological processes remain unclear and early identification of MCI remains challenging. Serum biomarkers correlated with cognitive impairment may aid characterizing the pattern of brain damage and predicting MCI.
Methods: Using ultrasensitive immunoassays and immunoprecipitation spectrometry, we longitudinally quantified serum neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), phosphorylated tau protein-181 (pTau-181), amyloid-β peptide 38 (Aβ38), Aβ40, Aβ42 and β-synuclein (βSyn) in HF patients within the Cognition.Matters-HF cohort study. Patients underwent cerebral magnetic resonance imaging and extensive domain-specific cognitive testing.
Results: In 104 analyzed patients (10% female, 64±10 years), except for NfL, all assessed biomarkers increased significantly (p<0.05 in repeated measurements analysis of covariance) within the 3-year observation with median annual percental changes of +36.6%/a for pTau, +4.6%/a for GFAP, +2.6%/a for βSyn, +0.6%/a for Aβ38, +0.5%/a for Aβ40, and +0.3%/a for Aβ42. The Aβ42/40 ratio decreased by -0.8%/a. Brain volume decreased age-appropriately by -0.3%/a, while there was a pathological increase of white matter hyperintensity (WMH) volume of 4.7%/a. Among all baseline biomarkers and temporal 3-year changes (Δ), ΔpTau showed the strongest correlation with ΔWMH (ρ=0.47; p<0.001). While most cognitive domains remained stable or even improved, intensity (p=0.041) and selectivity of attention (p=0.010) worsened over time, but their deterioration did not relate to the assessed biomarkers.
Conclusions: In this clinically stable HF cohort, a prominent increase of pTau related to pathological increase in WMH volume, whereas the associated subtle attentional changes were not reflected by biomarker changes.