The influence of sex on non-motor wearing-off in Parkinson's disease: A WORK-PD post-hoc study.

Introduction: The wearing-off phenomenon is characterized by the recurrence of motor and non-motor symptoms of Parkinsonism during a period free from levodopa. It is a pivotal aspect marking the end of the pharmacological "honeymoon" period in Parkinson's disease (PD). A growing body of literature is connecting sex with the likelihood of developing fluctuations.

Sainfoin ( spp.) crop ontology: supporting germplasm characterization and international research collaborations.

Sainfoin ( spp.) is a perennial forage legume that is also attracting attention as a perennial pulse with potential for human consumption. The dual use of sainfoin underpins diverse research and breeding programs focused on improving sainfoin lines for forage and pulses, which is driving the generation of complex datasets describing high dimensional phenotypes in the post-omics era.

Evaluating the Safety and Efficacy of Crenezumab vs Placebo in Adults With Early Alzheimer Disease: Two Phase 3 Randomized Placebo-Controlled Trials.

Importance: Alzheimer disease (AD), a neurodegenerative disease characterized by β-amyloid plaques and τ tangles in the brain, represents an unmet medical need with no fully approved therapeutics to modify disease progression.

Objective: To investigate the safety and efficacy of crenezumab, a humanized monoclonal immunoglobulin G4 antibody targeting β-amyloid oligomers, in participants with prodromal to mild (early) AD.

Design, Setting, And Participants: Two phase 3 multicenter randomized double-blind placebo-controlled parallel-group efficacy and safety studies of crenezumab in participants with early AD, CREAD and CREAD2, were initiated in 2016 and 2017, respectively, and were designed to evaluate the efficacy and safety of crenezumab in participants with early AD.

Patients with Increased Non-Ceruloplasmin Copper Appear a Distinct Sub-Group of Alzheimer's Disease: A Neuroimaging Study.

Background: Meta-analyses show that copper non-bound to ceruloplasmin (non-Cp Cu, also known as 'free' copper) in serum is higher in a percentage of Alzheimer's disease (AD) patients. Genetic heterogeneity in AD patients stratified on the basis of non-Cp Cu cut-off sustains the existence of a copper AD metabolic subtype.

Objective: In order to find evidence of the existence of a detectable metabolic subtype of AD associated to copper abnormalities, we explore the hypothesis of a neuroimaging pattern heterogeneity in an homogenous and well characterized AD population classified in two groups by the stratification of patients on the basis non-Cp Cu cut-off.

A Novel Method to Compute Breathing Volumes via Motion Capture Systems: Design and Experimental Trials.

Respiratory assessment can be carried out by using motion capture systems. A geometrical model is mandatory in order to compute the breathing volume as a function of time from the markers' trajectories. This study describes a novel model to compute volume changes and calculate respiratory parameters by using a motion capture system.

Optical measurement of breathing: algorithm volume calibration and preliminary validation on healthy trained subjects.

The use of optical technologies may be beneficial when measuring breathing biomechanics. The purpose of this study was twofold: i) to enhance the optoelectronic plethysmography (OEP) algorithm performance for the volume estimation by the use of a novel volume calibration procedure and ii) to compare the OEP volumes gained by a commercial optoelectronic system against actual respiratory volumes measured by a breath-by-breath gas analyzer (BbB). The OEP volume algorithm calibration was performed by the use of a novel volume calibration procedure based on both a calibrator device that delivered known volumes changes and one ad-hoc designed software for the static and dynamic calibration analysis.

Measurements of serum non-ceruloplasmin copper by a direct fluorescent method specific to Cu(II).

Background: Meta-analyses indicated the breakdown of copper homeostasis in the sporadic form of Alzheimer's disease (AD), comprising copper decreases within the brain and copper increases in the blood and the pool not bound to ceruloplasmin (non-Cp Cu, also known in the literature as "free" copper). The calculated non-Cp Cu (Walshe's) index has many limitations.

Methods: A direct fluorescent method for non-Cp Cu detection has been developed and data are presented herein.

Wearing-off detection in clinical practice: the wearing off real practice key (WORK-PD) study in Parkinson's disease.

Objective: Verifying the validity and feasibility of the WOQ-19 as a useful tool in routine clinical practice and in management of patients.

Methods: 532 consecutive Parkinson's disease (PD) patients were recruited from 6 different neurological outpatient units, specialized in movement disorders, of central Italy. Inclusion criteria were diagnosis of PD and any current pharmacological treatment of PD while exclusion criteria were evident cognitive or depressive impairment, infusion with dopamine agonists or Duodopa, or Deep Brain Stimulation therapy.

Value of serum nonceruloplasmin copper for prediction of mild cognitive impairment conversion to Alzheimer disease.

Objective: Meta-analyses show that nonbound ceruloplasmin (non-Cp) copper (also known as free or labile copper) in serum is higher in patients with Alzheimer disease (AD). It differentiates subjects with mild cognitive impairment (MCI) from healthy controls. However, a longitudinal study on an MCI cohort has not yet been performed to assess the accuracy of non-Cp copper for the prediction of conversion from MCI to AD during a long-term follow-up.

Sensorimotor Cortex Reorganization in Alzheimer's Disease and Metal Dysfunction: A MEG Study.

Objective. To verify whether systemic biometals dysfunctions affect neurotransmission in living Alzheimer's disease (AD) patients. Methods.

Movement-induced uncoupling of primary sensory and motor areas in focal task-specific hand dystonia.

Introduction: Due to growing evidence of sensorimotor integration impairment in focal task-specific hand dystonia, we aimed at describing primary sensory (S1) and primary motor (M1) cortex source activities and their functional cross-talk during a non-dystonia-inducing sensorimotor task free of biases generated by the interfering with the occurrence of dystonic movements.

Method: Magnetoencephalographic brain signals and opponens pollicis (OP) electromyographic activities were acquired at rest and during a simple isometric contraction performed either alone or in combination with median nerve stimulation. The task was performed separately with the right and left hand by eight patients suffering from focal task-specific hand dystonia and by eight healthy volunteers.

Antioxidant status and APOE genotype as susceptibility factors for neurodegeneration in Alzheimer's disease and vascular dementia.

Different factors interact to develop neurodegeneration in patients with dementia and other neurodegenerative disorders. Oxidative stress and the ε4 allele of apolipoprotein E (ApoE) are associated with significant alteration in lipid metabolism, in turn connected to a variety of neurodegenerative diseases and aging. Thus, a better understanding of the pathogenetic pathways associated with lipid dyshomeostasis may elucidate the causes of neurodegenerative processes.

Metal-score as a potential non-invasive diagnostic test for Alzheimer's disease.

The link between biometals and Alzheimer's disease (AD) has been investigated with a focus on local metal accumulations. In this work, we have looked at systemic metal changes and computed a score (M-score) based on metal disarrangements to discriminate patients with AD from patients with vascular dementia (VaD) and from controls. We measured serum levels of iron, copper, ceruloplasmin, transferrin, and total antioxidant capacity (TAS), performed Apolipoprotein E (APOE) genotyping and calculated non-ceruloplasmin copper ('free' copper') levels, transferrin saturation, total iron binding capacity, and ceruloplasmin-transferrin ratio (Cp/Tf) in 93 patients with AD, 45 patients with VaD, and 48 controls.

Linkage disequilibrium and haplotype analysis of the ATP7B gene in Alzheimer's disease.

Copper dyshomeostasis leading to a labile Cu(2+) not bound to ceruloplasmin ("free" copper) may influence Alzheimer's disease (AD) onset or progression. To investigate this hypothesis, we investigated ATP7B, the gene that controls copper excretion through the bile and concentrations of free copper in systemic circulation. Our study analyzed informative ATP7B single-nucleotide polymorphisms (SNPs) in a case-control population (n=515).

GSTM1 null genotype as risk factor for late-onset Alzheimer's disease in Italian patients.

Alzheimer's disease (AD) is the most common form of dementia in the elderly. The causes of AD are very complex but there is general agreement about the existence of a link between Alzheimer's disease and oxidative stress. The Glutathione S-transferases (GSTs) act to detoxify products of oxidation that cause damage to macromolecules.

Effects of hemochromatosis and transferrin gene mutations on iron dyshomeostasis, liver dysfunction and on the risk of Alzheimer's disease.

It is now accepted that transition metals, such as iron and copper, are involved in the pathogenesis of the Alzheimer's disease (AD) through their participation in toxic oxidative phenomena. In this context, hemochromatosis (Hfe) and transferrin (Tf) genes are of particular importance, since they play a key role in iron homeostasis. Also, signs of liver distress which accompany metal dysmetabolisms have been shown to be linked to AD.

Ceruloplasmin/Transferrin ratio changes in Alzheimer's disease.

The link between iron and Alzheimer's disease (AD) has been mainly investigated with a focus on the local accumulation of this metal in specific areas of the brain that are critical for AD. In the present study, we have instead looked at systemic variations of markers of iron metabolism. We measured serum levels of iron, ceruloplasmin, and transferrin and calculated the transferrin saturation and the ceruloplasmin to transferrin ratio (Cp/Tf).

Novel T719P AbetaPP mutation unbalances the relative proportion of amyloid-beta peptides.

A novel missense mutation (T719P) in the amyloid-beta protein precursor (AbetaPP) gene was discovered in a 46-year old patient affected by early onset familial Alzheimer's disease. Using surface enhanced laser desorption/ionization mass spectrometry (SELDI-TOF MS), we determined mass profiles of amyloid-beta peptides (Abeta) in cerebrospinal fluid (CSF) of the AbetaPP mutated patient, healthy control subjects (n = 10), and of two subjects carrying mutations in presenilins genes (PS) (i.e.

Ibuprofen treatment modifies cortical sources of EEG rhythms in mild Alzheimer's disease.

Objective: Non-steroidal anti-inflammatory drugs such as ibuprofen have a protective role on risk of Alzheimer's disease (AD). Here we evaluated the hypothesis that long-term ibuprofen treatment affects cortical sources of resting electroencephalographic (EEG) rhythms in mild AD patients.

Methods: Twenty-three AD patients (13 treated AD IBUPROFEN; 10 untreated AD PLACEBO) were enrolled.

Longitudinal prognostic value of serum "free" copper in patients with Alzheimer disease.

Background: Serum copper not bound to ceruloplasmin ("free") appears slightly elevated in patients with Alzheimer disease (AD). We explored whether a deregulation of the free copper pool can predict AD clinical worsening.

Methods: We assessed levels of copper, iron, zinc, transferrin, ceruloplasmin, peroxides, total antioxidant capacity, free copper, and apolipoprotein E genotype in 81 patients with mild or moderate AD, mean age 74.

An observational study on the influence of the APOE-epsilon4 allele on the correlation between 'free' copper toxicosis and EEG activity in Alzheimer disease.

Since many years the apolipoprotein E epsilon4 allele (APOE-epsilon4) is known to be associated with Alzheimer disease (AD) but the mechanisms of these associations remained unclear. In the last years, the potential pathogenetic role of 'free' copper (i.e.

Sensorimotor integration in focal task-specific hand dystonia: a magnetoencephalographic assessment.

To obtain a direct sensorimotor integration assessment in primary hand cortical areas (M1) of patients suffering from focal task-specific hand dystonia, magnetoencephalographic (MEG) and opponens pollicis electromyographic (EMG) activities were acquired during a motor task expressly chosen not to induce dystonic movements in our patients, to disentangle abnormalities indicating a possible substrate on which dystonia develops. A simple isometric contraction was performed either alone or in combination with median nerve stimulation, i.e.

PINK1 heterozygous rare variants: prevalence, significance and phenotypic spectrum.

Heterozygous rare variants in the PINK1 gene, as well as in other genes causing autosomal recessive parkinsonism, have been reported both in patients and healthy controls. Their pathogenic significance is uncertain, but they have been suggested to represent risk factors to develop Parkinson disease (PD). The few large studies that assessed the frequency of PINK1 heterozygotes in cases and controls yielded controversial results, and the phenotypic spectrum is largely unknown.