@article{TraubOttoSelletal.2022,
  author    = {Traub, Jan and Otto, Markus and Sell, Roxane and G{\"o}pfert, Dennis and Homola, Gy{\"o}rgy and Steinacker, Petra and Oeckl, Patrick and Morbach, Caroline and Frantz, Stefan and Pham, Mirko and St{\"o}rk, Stefan and Stoll, Guido and Frey, Anna},
  title     = {Serum phosphorylated tau protein 181 and neurofilament light chain in cognitively impaired heart failure patients},
  series = {Alzheimer's Research \& Therapy},
  volume    = {14},
  journal   = {Alzheimer's Research \& Therapy},
  doi       = {10.1186/s13195-022-01087-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300515},
  year      = {2022},
  abstract  = {Background Chronic heart failure (HF) is known to increase the risk of developing Alzheimer's dementia significantly. Thus, detecting and preventing mild cognitive impairment, which is common in patients with HF, is of great importance. Serum biomarkers are increasingly used in neurological disorders for diagnostics, monitoring, and prognostication of disease course. It remains unclear if neuronal biomarkers may help detect cognitive impairment in this high-risk population. Also, the influence of chronic HF and concomitant renal dysfunction on these biomarkers is not well understood. Methods Within the monocentric Cognition.Matters-HF study, we quantified the serum levels of phosphorylated tau protein 181 (pTau) and neurofilament light chain (NfL) of 146 extensively phenotyped chronic heart failure patients (aged 32 to 85 years; 15.1\% women) using ultrasensitive bead-based single-molecule immunoassays. The clinical work-up included advanced cognitive testing and cerebral magnetic resonance imaging (MRI). Results Serum concentrations of NfL ranged from 5.4 to 215.0 pg/ml (median 26.4 pg/ml) and of pTau from 0.51 to 9.22 pg/ml (median 1.57 pg/ml). We detected mild cognitive impairment (i.e., T-score < 40 in at least one cognitive domain) in 60\% of heart failure patients. pTau (p = 0.014), but not NfL, was elevated in this group. Both NfL (ρ = - 0.21; p = 0.013) and pTau (ρ = - 0.25; p = 0.002) related to the cognitive domain visual/verbal memory, as well as white matter hyperintensity volume and cerebral and hippocampal atrophy. In multivariable analysis, both biomarkers were independently influenced by age (T = 4.6 for pTau; T = 5.9 for NfL) and glomerular filtration rate (T = - 2.4 for pTau; T = - 3.4 for NfL). Markers of chronic heart failure, left atrial volume index (T = 4.6) and NT-proBNP (T = 2.8), were further cardiological determinants of pTau and NfL, respectively. In addition, pTau was also strongly affected by serum creatine kinase levels (T = 6.5) and ferritin (T = - 3.1). Conclusions pTau and NfL serum levels are strongly influenced by age-dependent renal and cardiac dysfunction. These findings point towards the need for longitudinal examinations and consideration of frequent comorbidities when using neuronal serum biomarkers.},
  language  = {en}
}
@article{TraubOttoSelletal.2022,
  author    = {Traub, Jan and Otto, Markus and Sell, Roxane and Homola, Gy{\"o}rgy A. and Steinacker, Petra and Oeckl, Patrick and Morbach, Caroline and Frantz, Stefan and Pham, Mirko and St{\"o}rk, Stefan and Stoll, Guido and Frey, Anna},
  title     = {Serum glial fibrillary acidic protein indicates memory impairment in patients with chronic heart failure},
  series = {ESC Heart Failure},
  volume    = {9},
  journal   = {ESC Heart Failure},
  number    = {4},
  doi       = {10.1002/ehf2.13986},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312736},
  pages     = {2626-2634},
  year      = {2022},
  abstract  = {Aims Cognitive dysfunction occurs frequently in patients with heart failure (HF), but early detection remains challenging. Serum glial fibrillary acidic protein (GFAP) is an emerging biomarker of cognitive decline in disorders of primary neurodegeneration such as Alzheimer's disease. We evaluated the utility of serum GFAP as a biomarker for cognitive dysfunction and structural brain damage in patients with stable chronic HF. Methods and results Using bead-based single molecule immunoassays, we quantified serum levels of GFAP in patients with HF participating in the prospective Cognition.Matters-HF study. Participants were extensively phenotyped, including cognitive testing of five separate domains and magnetic resonance imaging (MRI) of the brain. Univariable and multivariable models, also accounting for multiple testing, were run. One hundred and forty-six chronic HF patients with a mean age of 63.8 ± 10.8 years were included (15.1\% women). Serum GFAP levels (median 246 pg/mL, quartiles 165, 384 pg/mL; range 66 to 1512 pg/mL) did not differ between sexes. In the multivariable adjusted model, independent predictors of GFAP levels were age (T = 5.5; P < 0.001), smoking (T = 3.2; P = 0.002), estimated glomerular filtration rate (T = -4.7; P < 0.001), alanine aminotransferase (T = -2.1; P = 0.036), and the left atrial end-systolic volume index (T = 3.4; P = 0.004). NT-proBNP but not serum GFAP explained global cerebral atrophy beyond ageing. However, serum GFAP levels were associated with the cognitive domain visual/verbal memory (T = -3.0; P = 0.003) along with focal hippocampal atrophy (T = 2.3; P = 0.025). Conclusions Serum GFAP levels are affected by age, smoking, and surrogates of the severity of HF. The association of GFAP with memory dysfunction suggests that astroglial pathologies, which evade detection by conventional MRI, may contribute to memory loss beyond ageing in patients with chronic HF.},
  language  = {en}
}