Serial biomarker assessment provided stronger prognostic information than baseline measurements alone in clinically stable patients with chronic HF, and longitudinal increases in circulating amyloid-β peptides associated with cognitive decline, structural brain changes, and mortality.
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.
A stratified approach based on amyloid status is essential for the optimal application of blood-based biomarkers in monitoring disease progression and evaluating therapeutic efficacy in future clinical trials and precision medicine.
Keun You Kim, Hyunsun Ham, E. Yoon et al.· The journal of prevention of...· 0 citations
In cognitively unimpaired older adults, elevated blood p-tau217 was linked to faster shrinkage in AD-specific brain regions, whereas NfL and GFAP were associated with more widespread atrophy, with NfL also associated with accelerated WMH accumulation.
Martina Valletta, D. L. Vetrano, E. Laukka et al.· Annals of Neurology· 0 citations
Introduction Type 1 diabetes (T1D) is associated with increased risk of dementias and other neurodegenerative diseases. Plasma biomarkers of neurodegeneration and neuroinflammation hold utility in risk prediction and diagnosis of neurodegenerative disease and other neuropathology, but there remains a paucity of data in the T1D population. This study quantified plasma levels of biomarkers of neurodegeneration and neuroinflammation [phosphorylated tau-181 (pTau-181), total tau (Tau), amyloid beta 42/amyloid beta 40 (Aβ42/40), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL)], and tested associations with T1D and related characteristics. Methods This cross-sectional analysis of a subset of participants from the Coronary Artery Calcification in Type 1 Diabetes study included adults with and without T1D. Biomarker levels were quantified using Quanterix Simoa, then log-transformed and analyzed using linear regression models adjusted for age, body mass index (BMI), race and ethnicity, smoking status, and estimated glomerular filtration rate (eGFR). A subsequent sensitivity analysis included diabetic retinopathy (DR). Results 136 adults with T1D (n=90, age 52 years, 58% female, average HbA1c 7.7%) and without T1D (n=46, age 53 years, 57% female, average HbA1c 5.4%) were included. In fully adjusted models, T1D was associated with higher pTau-181 [estimate (pg/mL) 1.221, (95% confidence interval 1.003, 1.486) p=0.046], GFAP [1.296 (1.129, 1.489), p<0.001], and NfL [1.355 (1.162, 1.579), p<0.001], relative to adults without T1D. In the sensitivity analysis, relative to adults without T1D, T1D with moderate/severe DR was associated with higher pTau-181 [1.330 (1.063, 1.663), p=0.013], GFAP [1.369 (1.653, 1.608), p<0.001], and NfL [1.495 (1.252, 1.786), p<0.001], and T1D with none/mild DR was associated with higher GFAP [1.228 (1.046, 1.442), p=0.013] and NfL [1.235 (1.037, 1.470), p=0.018]. As compared to T1D with none/mild DR, T1D with moderate/severe DR was associated with higher NfL [1.211 (1.011, 1.451), p=0.038]. Across both models, eGFR was inversely associated with pTau-181, NfL, and Tau (p<0.05 for all). Discussion T1D is associated with a greater burden of plasma biomarkers of neurodegeneration and neuroinflammation, and microvascular complications such as DR and impaired kidney function may contribute to this burden. Further study is needed to fully characterize the interplay between these biomarkers and neuropathology in T1D.
Meghan E Pauley, Christina Coughlan, Fran Dong et al.· Frontiers in Immunology· 0 citations
BACKGROUND AND PURPOSE
Subjective cognitive decline (SCD) may precede mild cognitive impairment (MCI) and dementia. However, the prognosis of patients with amyloid-negative (A-) SCD remains unclear. We investigated whether baseline plasma and imaging biomarkers predict four-year clinical progression in A-SCD.
METHODS
Sixty-five individuals with A-SCD were followed for four years. Baseline plasma biomarkers-phosphorylated tau 181 (pTau181), glial fibrillary acidic protein, neurofilament light chain (NfL), and pTau181/Aβ42 ratio-and MRI markers (hippocampal volume and white matter hyperintensity [WMH] grade) were assessed. Outcomes included MCI conversion and cognitive progression defined as ≥1-point (Prog-1) or ≥2-point (Prog-2) decline in Korean Mini-Mental State Examination. Predictive performance was evaluated using multivariable logistic regression and bootstrap-validated receiver operating characteristic analyses.
RESULTS
Fourteen participants (21.5%) converted to MCI, and 24 (36.9%) were classified as Prog-1. Plasma biomarkers did not show consistent predictive performance across predefined endpoints (all p>0.05), although NfL demonstrated modest discrimination for MCI conversion (area under the curve [AUC] 0.686, p=0.008). Hippocampal volume demonstrated significant discriminative performance for MCI conversion (AUC 0.765, p=0.016) and Prog-1 (AUC 0.933, p<0.001). For Prog-2, hippocampal volume showed high discrimination (AUC 0.952, p<0.001). WMH grade also demonstrated significant discrimination for MCI conversion (AUC 0.835, p<0.001) and Prog-1 (AUC 0.857, p<0.001). Bootstrap analyses (1,000 iterations) tended to show higher AUC estimates for imaging markers compared with plasma biomarkers.
CONCLUSIONS
In this A-SCD cohort, hippocampal atrophy demonstrated more consistent prognostic performance than Alzheimer's disease-focused plasma biomarkers for predicting four-year conversion to MCI and cognitive decline, suggesting a potential role for MRI-based neurodegeneration markers in clinical risk stratification.
Bora Yoon, Hyuk-je Lee, Y. Hong et al.· Journal of Clinical Neurolog...· 1 citation
Higher plasma YKL‐40 was associated with greater white matter hyperintensity (WMH), whereas higher plasma GFAP was related to increased 18F‐florbetapir (FBP) standardized uptake value ratio (SUVR) and higher plasma p‐tau217 was associated with reduced MTL cortical thickness and hippocampal volume.
Batool Rizvi, Jenna N. Adams, Alison R. Bamford et al.· Alzheimer's & Dementia· 1 citation
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