Exceeding the Limits with Nutraceuticals: Looking Towards Parkinson's Disease and Frailty.

One of the most pressing challenges facing society today is the rising prevalence of physical and cognitive frailty. This geriatric condition makes older adults more vulnerable to disability, illness, and a heightened risk of mortality. In this scenario, Parkinson's disease (PD) and geriatric frailty, which share several common characteristics, are becoming increasingly prevalent worldwide, underscoring the urgent need for innovative strategies.

Variability of excessive daytime sleepiness and cataplexy according to seasonality: A study in central disorders of hypersomnolence.

Seasonality of excessive daytime sleepiness has been proposed, yet no research has specifically investigated its impact on daytime sleepiness and cataplexy in central disorders of hypersomnolence. This study examined seasonal variations in daytime sleepiness and cataplexy in narcolepsy type 1, narcolepsy type 2 and idiopathic hypersomnia. Patients included in the study were on stable pharmacological treatment, and participated in sleep medicine interviews to assess diurnal sleepiness and daytime napping and completed the Epworth Sleepiness Scale to assess excessive daytime sleepiness (Epworth Sleepiness Scale ≥ 10).

Haploinsufficiency of PDE2A causes in mice increased exploratory behavior associated with upregulation of neural nitric oxide synthase in the striatum.

Phosphodiesterase 2 A (PDE2A) function is stimulated by cGMP to catabolize cAMP. However, neurological and neurochemical effects of PDE2A deficiency are poorly understood. To address this gap, we studied behavioral characteristics and cerebral morpho-chemical changes of adult male heterozygous C57BL/6-PDE2A+/- (HET), and wild type C57BL/6-PDE2A+/+ (WT) mice.

Gastrointestinal Dysfunction Bears on the Clinical-Biological Profile of Parkinson's Disease.

Background: Gastrointestinal dysfunction (GID) accompanies any phase of Parkinson's disease (PD), underlying differential clinical-pathological trajectories.

Objective: To investigate associations between GID and peripheral immune or neurodegeneration-related markers in PD.

Methods: 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.

Changes in body composition revealed by bioelectrical impedance analysis reflect strength and motor performance in myotonic dystrophy type 2.

Introduction: In myotonic dystrophy type 2 (DM2), metabolic dysfunctions are frequent. Therefore, measurement of muscle mass and body composition by non-invasive methods could help in evaluating disease severity and progression. The aim of our study was to investigate, by means of bioelectrical impedance analysis (BIA), whether DM2 patients have an alteration in their body composition and if this finding correlates with strength and motor performances.

Sex hormones shape EEG-based functional connectivity in early-stage Parkinson's disease patients.

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.

Molecular and cellular determinants of L-Dopa-induced dyskinesia in Parkinson's Disease.

Treatment with L-3,4-dihydroxyphenylalanine (L-Dopa) compensates for decreased striatal dopamine (DA) levels and reduces Parkinson's disease (PD) symptoms. However, during disease progression, L-Dopa-induced dyskinesia (LID) develops virtually in all PD patients, making the control of PD symptoms difficult. Thus, understanding the mechanisms underlying LID and the control of these motor abnormalities is a major issue in the care of PD patients.

Cortical Functional Connectivity Changes in the Body-First and Brain-First Subtypes of Parkinson's Disease.

Background: Rapid eye movement (REM) sleep behavior disorder (RBD) may precede motor symptoms in Parkinson's disease (PD) by years. According to a recent hypothesis, premotor RBD (pRBD) is a marker of the PD body-first subtype, where synucleinopathy originates from the peripheral autonomic nervous system. Conversely, in the brain-first subtype, pathology would arise in the brain.

Age of onset moderates the effects of Vascular Risk Factors on Neurodegeneration, Blood-Brain-Barrier permeability, and cognitive decline in Alzheimer's Disease.

Background: The role of Vascular risk factors (VRFs) in the progression of Alzheimer's Disease (AD) and cognitive decline remains to be elucidated, with previous studies resulting in conflicting findings. The possible impact of age-specific mechanisms of resilience/vulnerability is an under addressed issue. We evaluated the association of VRFs with markers of amyloid deposition, neurodegeneration, and blood-brain-barrier (BBB) permeability (Albumin quotient, Qalb), stratifying patients into early-onset (< 65, EOAD), classic late-onset (65-75, cLOAD) and very late-onset (> 75, vLOAD), to evaluate the moderating effect of age of onset.

Systemic inflammation accelerates neurodegeneration in a rat model of Parkinson's disease overexpressing human alpha synuclein.

Increasing efforts have been made to elucidate how genetic and environmental factors interact in Parkinson's disease (PD). In the present study, we assessed the development of symptoms on a genetic PD rat model that overexpresses human α-synuclein (Snca) at a presymptomatic age, exposed to a pro-inflammatory insult by intraperitoneal injection of lipopolysaccharide (LPS), using immunohistology, high-dimensional flow cytometry, constant potential amperometry, and behavioral analyses. A single injection of LPS into WT and Snca rats triggered long-lasting increase in the activation of pro-inflammatory microglial markers, monocytes, and T lymphocytes.

Hydrogen Sulfide Modulates Astrocytic Toxicity in Mouse Spinal Cord Cultures: Implications for Amyotrophic Lateral Sclerosis.

Hydrogen sulfide (HS), a known inhibitor of the electron transport chain, is endogenously produced in the periphery as well as in the central nervous system, where is mainly generated by glial cells. It affects, as a cellular signaling molecule, many different biochemical processes. In the central nervous system, depending on its concentration, it can be protective or damaging to neurons.

Insular monoaminergic deficits in prodromal α-synucleinopathies.

Methods: This study assessed data from two cohorts of patients with alpha-synucleinopathies (University of Brescia and University of Rome Tor-Vergata cohorts). Consecutive participants with video-polysomnography-confirmed iRBD, Parkinson's disease (PD), dementia with Lewy bodies (DLB) and controls underwent neurological, clinical and I-FP-CIT SPECT imaging assessments. Individuals with iRBD were longitudinally monitored to collect clinical phenoconversion to PD or DLB.

Positron Emission Tomography/Computed Tomography Imaging in Therapeutic Clinical Trials in Alzheimer's Disease: An Overview of the Current State of the Art of Research.

The integration of positron emission tomography/computed tomography (PET/CT) has revolutionized the landscape of Alzheimer's disease (AD) research and therapeutic interventions. By combining structural and functional imaging, PET/CT provides a comprehensive understanding of disease pathology and response to treatment assessment. PET/CT, particularly with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG), facilitates the visualization of glucose metabolism in the brain, enabling early diagnosis, staging, and monitoring of neurodegenerative disease progression.

Orexin Receptor Antagonists for the Prevention and Treatment of Alzheimer's Disease and Associated Sleep Disorders.

Orexins/hypocretins are neuropeptides produced by the hypothalamic neurons, binding two G-protein coupled receptors (orexin 1 and orexin 2 receptors) and playing a critical role in regulating arousal, wakefulness, and various physiological functions. Given the high prevalence of sleep disturbances in Alzheimer's disease (AD) and their reported involvement in AD pathophysiology, the orexin system is hypothesized to contribute to the disease pathogenesis. Specifically, recent evidence suggests that orexin's influence may extend beyond sleep regulation, potentially affecting amyloid-β and tau pathologies.

Functional efficacy of the MAO-B inhibitor safinamide in murine substantia nigra pars compacta dopaminergic neurons in vitro: A comparative study with tranylcypromine.

Safinamide (SAF) is currently used to treat Parkinson's disease (PD) symptoms based on its theoretical ability to potentiate the dopamine (DA) signal, blocking monoamine oxidase (MAO) B. The present work aims to highlight the functional relevance of SAF as an enhancer of the DA signal, by evaluating its ability to prolong recovery from DA-mediated firing inhibition of DAergic neurons of the substantia nigra pars compacta (SNpc), compared to another MAO antagonist, tranylcypromine (TCP). Using multielectrode array (MEA) and single electrode extracellular recordings of spontaneous spikes from presumed SNpc DAergic cells in vitro, we show that SAF (30 μM) mildly prolongs the DA-mediated firing inhibition, as opposed to the profound effect of TCP (10 μM).

Immunometabolic Signature and Tauopathy Markers in Blood Cells of Progressive Supranuclear Palsy.

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.

Stage-dependent phosphoproteome remodeling of Parkinson's disease blood cells.

The complexity and heterogeneity of PD necessitate advanced diagnostic and prognostic tools to elucidate its molecular mechanisms accurately. In this study, we addressed this challenge by conducting a pilot phospho-proteomic analysis of peripheral blood mononuclear cells (PBMCs) from idiopathic PD patients at varying disease stages to delineate the functional alterations occurring in these cells throughout the disease course and identify key molecules and pathways contributing to PD progression. By integrating clinical data with phospho-proteomic profiles across various PD stages, we identify potential stage-specific molecular signatures indicative of disease progression.

Contribution of testosterone and estradiol in sexual dimorphism of early-onset Parkinson's disease.

Early-onset Parkinson's disease (EOPD) occurs during the fertile life, when circulating neuroactive sex hormones might enhance the sexual dimorphism of the disease. Here, we aimed to examine how sex hormones can contribute to sex differences in EOPD patients. A cohort of 34 EOPD patients, 20 males and 14 females, underwent comprehensive clinical evaluation of motor and non-motor disturbances.

Poor Adherence to the Mediterranean Diet and Sleep Disturbances Are Associated with Migraine Chronification and Disability among an Adult Population in the Lazio Region, Italy.

Lifestyle factors, such as diet and sleep quality, are receiving increasing interest as accessible therapeutic approaches to migraine. The Mediterranean diet (MD) has shown clear benefits in cardiovascular and metabolic diseases, as well as in sleep patterns. Here, our objective was to identify the impact of adherence to the MD and other lifestyle factors on the clinical burden of migraine.

Insular and limbic abnormal functional connectivity in early-stage Parkinson's disease patients with autonomic dysfunction.

Autonomic symptoms in Parkinson's disease result from variable involvement of the central and peripheral systems, but many aspects remain unclear. The analysis of functional connectivity has shown promising results in assessing the pathophysiology of Parkinson's disease. This study aims to investigate the association between autonomic symptoms and cortical functional connectivity in early Parkinson's disease patients using high-density EEG.