Background: Pulmonary dysfunction is associated with elevated risk of cognitive decline. However, the mechanism underlying this relationship has not been fully investigated. In this study, we investigate the relationships between pulmonary function, cerebral small vessel disease (CSVD) markers, cortical thickness, and the Mini-Mental Status Examination (MMSE) scores in cognitively normal individuals.
Methods: We used a cross-sectional study design. We identified 1924 patients who underwent pulmonary function testing, three-dimensional brain magnetic resonance imaging (MRI), and the MMSE. Pulmonary function was analyzed according to the quintiles of percentage predicted values (% pred) for forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV). Regarding CSVD markers, we visually rated white matter hyperintensities (WMH) and manually counted lacunes and microbleeds. Cortical thickness was measured by surface-based methods.
Results: Compared with the highest quintile of FVC, the lowest quintile of FVC (% pred) showed a higher risk of WMH (OR 1.98, 95% CI: 1.21-3.24) and lacunes (OR 1.86, 95% CI: 1.12-3.08). There were no associations between FVC or FEV and cortical thickness. Low FVC, but not FEV, was associated with low MMSE scores. Path analyses showed that WMH partially mediated the positive relationship between FVC (% pred) and MMSE score.
Conclusions: Our findings suggested that decreased pulmonary function was associated with increased CSVD burdens, which in turn wass associated with decreased cognition, even in cognitively normal subjects.
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http://dx.doi.org/10.1016/j.nicl.2019.102140 | DOI Listing |
The BMT CTN 1703 phase III trial confirmed that graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) results in superior GVHD-free, relapse-free survival (GRFS) compared with Tac/methotrexate (MTX) prophylaxis. This companion study assesses the effect of these regimens on patient-reported outcomes (PROs). Using the Lee Chronic GVHD Symptom Score and PROMIS subscales (physical function, GI symptoms, social role satisfaction) as primary end points and hemorrhagic cystitis symptoms and Lee subscales as secondary end points, responses from English and Spanish speakers were analyzed at baseline and days 100, 180, and 365 after transplant.
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Oxylipins, diverse lipid mediators derived from fatty acids, play key roles in respiratory physiology, but the contribution of lung structural cells to this diverse profile is not well understood. This study aimed to characterize the oxylipin profiles of airway smooth muscle (ASM), lung fibroblasts (HLF), and epithelial (HBE) cells and define how they shift when they are exposed to stimuli related to contractility, fibrosis, and inflammation. Using HPLC-MS/MS, 162 oxylipins were measured in baseline media from cultured human ASM, HLF, and HBE cells as well as after stimulation with modulators of contractility and central regulators of fibrosis/inflammation.
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Laboratory of Obesity and Aging Research, Cardiovascular Branch, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892.
Mitochondrial endonuclease G (EndoG) contributes to chromosomal degradation when it is released from mitochondria during apoptosis. It is presumed to also have a mitochondrial function because EndoG deficiency causes mitochondrial dysfunction. However, the mechanism by which EndoG regulates mitochondrial function is not known.
View Article and Find Full Text PDFSci Adv
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Yale Cardiovascular Research Center, Yale School of Medicine, New Haven, CT 06511, USA.
Fluid shear stress (FSS) from blood flow sensed by vascular endothelial cells (ECs) determines vessel behavior, but regulatory mechanisms are only partially understood. We used cell state transition assessment and regulation (cSTAR), a powerful computational method, to elucidate EC transcriptomic states under low shear stress (LSS), physiological shear stress (PSS), high shear stress (HSS), and oscillatory shear stress (OSS) that induce vessel inward remodeling, stabilization, outward remodeling, or disease susceptibility, respectively. Combined with a publicly available database on EC transcriptomic responses to drug treatments, this approach inferred a regulatory network controlling EC states and made several notable predictions.
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