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Background: Atrial Fibrillation (AF) is associated with an increased risk of stroke and systemic embolism. Several studies have suggested that female AF patients could have a greater risk for stroke. There is scarce information about clinical characteristics and use of antithrombotic therapies in Latin American patients with nonvalvular AF. Objective: To describe the gender differences in clinical characteristics, thromboembolic risk, and antithrombotic therapy of patients with nonvalvular AF recruited in Mexico, an upper middle-income country, into the prospective national CARMEN-AF Registry. Methods: A total of 1423 consecutive patients, with at least one thromboembolic risk factor were enrolled in CARMEN-AF Registry during a three-year period (2014–2017). They were categorized according to Gender. Results: Overall, 48.6% were women, mean age 70 ± 12 years. Diabetes, smoking, alcoholism, non-ischemic cardiomyopathy, coronary artery disease, and obstructive sleep apnea were higher in men. Most women were found with paroxysmal AF (40.6%), and most men with permanent AF (44.0%). No gender differences were found in the use of vitamin K antagonists (VKA) (30.5% in women vs. 28.0% in men). No gender differences were found in the use of direct oral anticoagulants (DOAC) (33.8% women vs 35.4% men). Conclusions: CARMEN-AF Registry demonstrates that in Mexico, regardless of gender, a large proportion of patients remain undertreated. No gender differences were found in the use of VKA or DOAC. Keywords: Atrial fibrillation, Gender, Thromboembolic risk, Antithrombotic therapy, Stroke, Mexico

Study Objectives: The body-first Parkinson's disease (PD) hypothesis suggests initial gut Lewy body pathology initially propagates to the pons before reaching the substantia nigra, and subsequently progresses to the diencephalic and cortical levels, a disease course presumed to likely occur in PD with rapid eye movement sleep behavior disorder (RBD). We aimed to explore the potential association between colonic phosphorylated alpha-synuclein histopathology (PASH) and diencephalic or cortical dysfunction evidenced by non-rapid eye movement (NREM) sleep and wakefulness polysomnographic markers., Methods: In a study involving 43 patients with PD who underwent clinical examination, rectosigmoidoscopy, and polysomnography, we detected PASH on colonic biopsies using whole-mount immunostaining. We performed a visual semi-quantitative analysis of NREM sleep and wake electroencephalography (EEG), confirmed it with automated quantification of spindle and slow wave features of NREM sleep, and the wake dominant frequency, and then determined probable Arizona PD stage classifications based on sleep and wake EEG features., Results: The visual analysis aligned with the automated quantified spindle characteristics and the wake dominant frequency. Altered NREM sleep and wake parameters correlated with markers of PD severity, colonic PASH, and RBD diagnosis. Colonic PASH frequency also increased in parallel to probable Arizona PD stage classifications., Conclusions: Colonic PASH is strongly associated with widespread brain sleep and wake dysfunction, suggesting an extensive diffusion of the pathologic process in PD. Visual and automated analyses of polysomnography signals provide useful markers to gauge covert brain dysfunction in PD., Clinical Trial: Name: SYNAPark, URL: https://clinicaltrials.gov/study/NCT01748409, registration: NCT01748409., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: The body-first Parkinson's disease (PD) hypothesis suggests initial gut Lewy body pathology that propagates to the pons before reaching the substantia nigra, and subsequently progresses to the diencephalic and cortical levels. This disease course may also be the most likely in PD with rapid eye movement sleep behavior disorder (RBD)., Objectives: We aimed to explore the potential association between colonic phosphorylated alpha-synuclein histopathology (PASH) and diencephalic or cortical dysfunction evidenced by non-rapid eye movement (NREM) sleep and wakefulness polysomnographic markers., Methods: In a study involving 43 patients with PD who underwent clinical examination, rectosigmoidoscopy, and polysomnography, we detected PASH on colonic biopsies using whole-mount immunostaining. We performed a visual semi-quantitative and automated quantification of spindle and slow wave features of NREM sleep, and the wake dominant frequency, and then determined Braak and Arizona stage classifications for PD severity based on sleep and wake electroencephalographic features., Results: The visual analysis aligned with the automated quantified spindle characteristics and the wake dominant frequency. Altered NREM sleep and wake parameters correlated with markers of PD severity, colonic PASH, and RBD diagnosis. Colonic PASH frequency also increased in parallel to presumed PD Braak and Arizona stage classifications., Conclusions: Colonic PASH in PD is strongly associated with widespread brain sleep and wake dysfunction, pointing toward likely extensive diffusion of the pathological process in the presumptive body-first PD phenotype. Visual and automated analyses of polysomnography signals provide useful markers to gauge covert brain dysfunction in PD., Statement of Significance: The presence of gut synucleinopathy in Parkinson's disease can be linked to the body-first hypothesis in its pathophysiology. This study, performed in a cohort of 43 patients with Parkinson's disease that underwent clinical assessment, rectosigmoidoscopy and polysomnography, provides evidence that colonic neuropathology in Parkinson's disease is associated with widespread brain dysfunction, as evaluated by wake and non-rapid eye movement sleep polysomnographic markers. Our results support the assumption of an extensive diffusion of the pathological process to diencephalic and neocortical structures in the presumptive body-first phenotype. They also suggest the use of routine polysomnography in phenotyping patients with Parkinson's disease. Future studies should investigate the brain diffusion pattern and its sleep markers in the hypothesized brain-first phenotype of Parkinson's disease.