Search

Background Objective Methods Results Conclusions Gastrointestinal dysfunction (GID) accompanies any phase of Parkinson's disease (PD), underlying differential clinical‐pathological trajectories.To investigate associations between GID and peripheral immune or neurodegeneration‐related markers in PD.One‐hundred‐and‐fourteen patients (n = 55 de novo, DN; n = 59 middle‐advanced, MA) completed the Gastrointestinal Dysfunction Scale for PD (GIDS‐PD), and other motor and non‐motor scales; paired measurement of amyloid‐β42, amyloid‐β42β/β40, total‐tau, phosphorylated‐181‐tau, total α‐synuclein CSF levels, albumin ratio, and peripheral blood cell count were collected. Group and correlation analyses were performed.MA patients had greater GID than DN. GIDS‐PD scores directly correlated with MDS‐UPDRS‐III and non‐motor scores in both groups, although more in DN. GIDS‐PD scores were directly associated with α‐synuclein and inversely with lymphocytes only in DN; conversely, they were positively associated with tau proteins and albumin ratio, and negatively with amyloid‐β‐peptides in both groups.The burden of GID increases along the PD course with associated stage‐specific clinical‐biological patterns. [ABSTRACT FROM AUTHOR]

Background: Peripheral immune cells critically contribute to the clinical‐pathological progression of neurodegenerative diseases and also represent a reliable frame for translational applications. However, data on progressive supranuclear palsy (PSP) are almost scarce in this regard. Objective: Our goal is to provide a broad biological characterization of peripheral immune cells in a selected PSP cohort. Methods: Seventy‐one PSP patients scored on the PSP Rating Scale (PSPRS), and 59 controls were enrolled. The blood cell count was collected, together with the neutrophil‐to‐lymphocyte ratio (NLR) calculation. In a subgroup of patients and controls, the peripheral blood mononuclear cells (PBMCs) were analyzed by the mitochondrial bioenergetic performance and the western blot assay of the nuclear factor erythroid 2‐related factor (NRF2)/heme oxygenase 1 (HO‐1) pathway and the total tau (t‐tau) and phosphorylated tau (p‐tau) proteins. Case–control comparison and correlation analyses were performed. Results: PSP patients had a NLR higher than controls, with increased circulating neutrophils. The leukocyte metabolism was also globally increased and the NRF2/HO‐1 pathway activated in patients. P‐tau, but not t‐tau, significantly accumulated in PSP PBMCs and inversely correlated with the PSPRS. Conclusions: PSP displays a systemic inflammatory shift of the peripheral immunity, which may justify a metabolic reprogramming of the blood leukocytes. Consistently, the NRF2/HO‐1 pathway, a master regulator of inflammatory and metabolic response, was activated. PBMCs also engulf tau proteins, especially p‐tau, in a way inverse to the disease severity, allowing for a peripheral tracking of tauopathy in patients. Immunometabolic targets may, therefore, gain relevance to PSP in biomarker or therapeutic purposes. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background and purpose: Idiopathic normal pressure hydrocephalus (iNPH) pathogenesis is multifactorial. Systemic inflammation might have a role in gathering clinical–pathological trajectories. We aimed to shape the peripheral immune profile of iNPH and establish correlations with cerebrospinal fluid (CSF) markers, ventricular enlargement, and clinical outcomes. Methods: We conducted a single‐center retrospective–longitudinal study, including 38 iNPH patients and 38 controls. Baseline iNPH Grading Scale and modified Rankin Scale (mRS) scores were collected with peripheral blood cell count, CSF amyloid‐β42 (Aβ42), total tau (t‐tau), phosphorylated‐181‐tau, and Evans index. Depending on 5‐year outcome, iNPH patients were grouped into "poor outcome" (PO; mRS ≥ 5) and "favorable outcome" (FO; mRS < 5). Biomarkers were compared and correlated with each other. Receiver operating characteristic analysis was performed. Results: iNPH patients compared to controls had higher neutrophil‐to‐lymphocyte ratio (NLR; 2.43 ± 1.04 vs. 1.61 ± 0.47, p < 0.001), higher neutrophils (4.22 ± 0.86 1000/mL vs. 3.48 ± 1.34, p = 0.033), and lower lymphocytes (1.45 ± 0.55 1000/mL vs. 2.07 ± 0.86, p = 0.038), with the expected CSF biomarkers signature. In the patients' cohort, NLR was associated directly with t‐tau and inversely with Aβ42. NLR directly correlated with Evans index. PO patients compared to those with FO had higher NLR (3.25 ± 1.40 vs. 2.01 ± 0.77, p = 0.035) and higher t‐tau (274.76 ± 114.39 pg/mL vs. 150.28 ± 72.62, p = 0.017), with an area under the curve of 0.786 and 0.793, respectively. Conclusions: iNPH patients present a proinflammatory state associated with neurodegeneration and predicting poor clinical outcome. Systemic inflammation represents a factor in the clinical–pathological progression of iNPH, and the NLR emerges as a potential prognostic index. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) epidemiology and clinical features are sexually dimorphic. However, there are no data based on EEG functional connectivity (FC). Likewise, the contribution of sex hormones on brain FC has never been evaluated. Here, we aimed to investigate the association between biological sex and sex hormones on cortical FC changes in PD using high-density EEG. This study involved 69 early-stage PD patients (F/M 27/42) and 69 age-matched healthy controls (HC) (F/M 30/39). Sex hormone levels (total-testosterone (TT), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH)) were assessed in PD patients. Data were recorded with a 64-channel EEG system. Source reconstruction method was used to identify brain activity. Cortico-cortical FC was analysed based on the weighted phase-lag index (wPLI) in θ-α-β-low γ bands. Network-based statistic (NBS) was used to compare FC between genders in HC and PD and to study the relationship between FC and sex hormones in PD. PD exhibited a hypoconnected network at θ and α bands and a hyperconnected network at β band compared to HC. Male HC showed a hyperconnected network at α-band compared to female HC. Conversely, males with PD showed a hypoconnected network at α-band compared to females with PD. In females and males with PD, E2 positively correlated with α-FC, while gonadotropins positively correlated with β-FC. TT positively correlated with the θ-FC only in males. Sex hormones shape EEG-FC in both males and females with PD, supporting their major influence on PD pathophysiology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)