Altered gut microbiota may trigger or accelerate alpha-synuclein aggregation in the enteric nervous system in Parkinson's disease (PD). While several previous studies observed gut microbiota alterations in PD, findings like diversity indices, and altered bacterial taxa itself show a considerable heterogeneity across studies. We recruited 179 participants, of whom 101 fulfilled stringent inclusion criteria. Subsequently, the composition of the gut microbiota in 71 PD patients and 30 healthy controls was analyzed, sequencing V3-V4 regions of the bacterial 16S ribosomal RNA gene in fecal samples. Our goal was (1) to evaluate whether gut microbiota are altered in a southern German PD cohort, (2) to delineate the influence of disease duration, stage, and motor impairment, and (3) to investigate the influence of PD associated covariates like constipation and coffee consumption. Aiming to control for a large variety of covariates, strict inclusion criteria were applied. Finally, propensity score matching was performed to correct for, and to delineate the effect of remaining covariates (non-motor symptom (NMS) burden, constipation, and coffee consumption) on microbiota composition. Prior to matching altered abundances of distinct bacterial classes, orders, families, and genera were observed. Both, disease duration, and stage influenced microbiome composition. Interestingly, levodopa equivalent dose influenced the correlation of taxa with disease duration, while motor impairment did not. Applying different statistical tests, and after propensity score matching to control for NMS burden, constipation and coffee consumption, Faecalibacterium and Ruminococcus were most consistently reduced in PD compared to controls. Taken together, similar to previous studies, alterations of several taxa were observed in PD. Yet, further controlling for PD associated covariates such as constipation and coffee consumption revealed a pivotal role of these covariates. Our data highlight the impact of these PD associated covariates on microbiota composition in PD. This suggests that altered microbiota may mediate the protective effect of i.e., coffee consumption and the negative effect of constipation in PD.

Background and Objectives:In patients with lobar intracerebral hemorrhage(ICH) etiological characterization represents a trade-off between feasibility, resource allocation, and diagnostic certainty. This study investigated the accuracy and clinical utility of the simplified Edinburgh CT criteria to identify underlying cerebral amyloid angiopathy(CAA).Methods:This external validation analyzed 210 consecutive patients with lobar ICH and available CT&MRI studies from a prospective single-center observational cohort study(2006-2015,UKER-ICH,NCT03183167). We investigated the simplified Edinburgh CT-based criteria’s inter-rater variability and diagnostic accuracy for identification of ICH associated with probable CAA according to MRI-based modified Boston criteria as a reference standard. We evaluated the simplified Edinburgh criteria’s utility by decision curve analysis, comparing the theoretical clinical net-benefit(weighted benefit–harm at varying threshold probabilities) of the high-risk category(finger-like-projections and subarachnoid hemorrhage) for ruling-in and the low-risk category(neither finger-like-projections nor subarachnoid hemorrhage) for ruling-out with the assumptions of no or all patients having CAA(default-strategies).Results:Of 210 patients, 70(33.3%) had high-risk, 67(31.9%) had medium-risk, and 73(34.8%) had low-risk for CAA associated ICH according to simplified Edinburgh CT criteria, showing moderate inter-rater variability. Discrimination was good(AUROC:0.74,95%CI 0.67–0.81) without evidence of poor calibration(Hosmer–Lemeshow,p=0.54) for validation of MRI-based diagnosis of probable CAA(n=94/210,44.8%). The rule-in criteria, i.e. high-risk, had 87.1%(79.3-92.3) specificity, and the rule-out criteria, i.e. low-risk, had 80.9%(71.1-88.0) sensitivity. Decision curve analysis suggested a theoretical clinical net-benefit for ruling-in but not for ruling-out probable CAA compared to default-strategies.Discussion:Applying the simplified Edinburgh CT criteria during diagnostic work-up seems clinically useful and may accurately identify CAA in patients with lobar ICH.Classification of Evidence:This study provides Class II evidence that in patients with lobar hemorrhages, simplified Edinburgh Criteria accurately identifies those at high risk of CAA.

IMPORTANCE Intracerebral hemorrhage (ICH) contributes significantly to the global burden of disease. OBJECTIVE To examine the association of ICH and secondary injury with disability-adjusted lifeyears (DALYs) for the individual patient.

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