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Serum immune markers and disease progression in an incident Parkinson's disease cohort (ICICLE-PD)

BACKGROUND: The immune system is a promising therapeutic target for disease modification in Parkinson's disease (PD), but appropriate immune-related biomarkers must be identified to allow patient stratification for trials and tracking of therapeutic effects. The objective of this study was to investigate whether immune markers in peripheral blood are candidate prognostic biomarkers through determi

Case management for older persons with multi-morbidity. Experiences of an intervention from the perspectives of older persons, family members, case managers and health and social care staff members

Complex health systems make it difficult to ensure a continuity of care for older persons with multi-morbidity, and risk fragmented care. Fragmented care could affect the quality and safety of the care provided. Case management could provide an approach to counteract this unfavourable situation. Case management is practised by case managers and aims to improve the coordination of healthcare and soComplex health systems make it difficult to ensure a continuity of care for older persons with multi-morbidity, and risk fragmented care. Fragmented care could affect the quality and safety of the care provided. Case management could provide an approach to counteract this unfavourable situation. Case management is practised by case managers and aims to improve the coordination of healthcare and so

Hypothalamic volume loss is associated with reduced melatonin output in Parkinson's disease

BACKGROUND: Recent studies have suggested that melatonin-a hormone produced by the pineal gland under circadian control-contributes to PD-related sleep dysfunction. We hypothesized that degenerative changes to the neural structures controlling pineal function (especially the suprachiasmatic nuclei of the anterior hypothalamus) may be responsible for reduced melatonin output in these patients. We c

Development and external validation of a prognostic model in newly diagnosed Parkinson disease

OBJECTIVE: To develop a prognostic model to predict disease outcomes in individual patients with Parkinson disease (PD) and perform an external validation study in an independent cohort.METHODS: Model development was done in the Comorbidity and Aging in Rehabilitation Patients: The Influence on Activities (CARPA) cohort (Netherlands). External validation was performed using the Cambridgeshire Park

Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures

Recent studies indicate that selective noradrenergic (atomoxetine) and serotonergic (citalopram) reuptake inhibitors may improve response inhibition in selected patients with Parkinson's disease, restoring behavioral performance and brain activity. We reassessed the behavioral efficacy of these drugs in a larger cohort and developed predictive models to identify patient responders. We used a doubl

Characterization and Visualization of Vesicles in the Endo-Lysosomal Pathway with Surface-Enhanced Raman Spectroscopy and Chemometrics

Surface-enhanced Raman spectroscopy (SERS) is an ultrasensitive vibrational fingerprinting technique widely used in analytical and biosensing applications. For intracellular sensing, typically gold nanoparticles (AuNPs) are employed as transducers to enhance the otherwise weak Raman spectroscopy signals. Thus, the signature patterns of the molecular nanoenvironment around intracellular unlabeled A

Hippocampal dysfunction defines disease onset in Huntington's disease

BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterised by a triad of motor, psychiatric and cognitive deficits with the latter classically attributed to disruption of frontostriatal networks. However, emerging evidence from animal models of HD suggests that some of the early cognitive deficits may have a hippocampal basis. The objective of this stud

Different decision deficits impair response inhibition in progressive supranuclear palsy and Parkinson's disease

Progressive supranuclear palsy and Parkinson's disease have distinct underlying neuropathology, but both diseases affect cognitive function in addition to causing a movement disorder. They impair response inhibition and may lead to impulsivity, which can occur even in the presence of profound akinesia and rigidity. The current study examined the mechanisms of cognitive impairments underlying disin

Advancing pharmacotherapy for treating Huntington's disease : a review of the existing literature

INTRODUCTION: Huntington's disease (HD) is an incurable chronic neurodegenerative disorder that typically presents in mid-life with a range of motor, cognitive and affective problems. Patients are currently managed using a combination of drug treatments and non-pharmacological therapies but at present there is no "gold standard" treatment for any aspect of the disease.AREAS COVERED: In this review

Anticholinergic Load : Is there a Cognitive Cost in Early Parkinson's Disease?

We evaluated the effect of anticholinergic burden on 219 participants with incident Parkinson's disease (PD) and 99 controls at study baseline and 18 months. Anticholinergic burden for each individual was calculated and summed according to the Anticholinergic Drug Scale (ADS). Medication with anticholinergic activity was more commonly prescribed in PD compared to controls, although mean ADS scores

Novel Nut and Bolt Task Quantifies Motor Deficits in Premanifest and Manifest Huntington's Disease

BACKGROUND: We investigated the use of a simple novel nut and bolt task in premanifest and manifest Huntington's disease (HD) patients to detect and quantify motor impairments at all stages of the disease.METHODS: Premanifest HD (n=24), manifest HD (n=27) and control (n=32) participants were asked to screw a nut onto a bolt in one direction, using three different sized bolts with their left and ri

Tracking Parkinson's : Study Design and Baseline Patient Data

BACKGROUND: There is wide variation in the phenotypic expression of Parkinson's disease (PD), which is driven by both genetic and epidemiological influences.OBJECTIVES: To define and explain variation in the clinical phenotype of PD, in relation to genotypic variation.METHODS: Tracking Parkinson's is a multicentre prospective longitudinal epidemiologic and biomarker study of PD. Patients attending

Rating Apathy in Huntington’s Disease : Patients and Companions Agree

BACKGROUND: Apathy is a common feature of Huntington’s disease (HD), even from early disease. However, patients are believed to lack insight into their own apathy and therefore clinicians and/or companions are relied upon to estimate the extent of a patient’s apathy. In addition, the evolution of apathy over time in HD has not been unequivocally established. OBJECTIVEs: The purpose of this study w

A simple assessment model to quantifying the dynamic hippocampal neurogenic process in the adult mammalian brain

Adult hippocampal neurogenesis is a highly dynamic process in which new cells are born, but only some of which survive. Of late it has become clear that these surviving newborn neurons have functional roles, most notably in certain forms of memory. Conventional methods to look at adult neurogenesis are based on the quantification of the number of newly born neurons using a simple cell counting met

Antidopaminergic Medication is Associated with More Rapidly Progressive Huntington's Disease

BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder leading to progressive motor, cognitive and functional decline. Antidopaminergic medications (ADMs) are frequently used to treat chorea and behavioural disturbances in HD.OBJECTIVE: We aimed to assess how the use of such medications was associated with the severity and progression of the motor aspects of the

Gray and white matter imaging : A biomarker for cognitive impairment in early Parkinson's disease?

BACKGROUND: The aim of this work was to investigate the cortical and white matter changes that underlie cognitive impairment in patients with incident Parkinson's disease (PD) disease using voxel-based morphometry and diffusion tensor imaging.METHODS: Newly diagnosed nondemented PD (n = 125) and control subjects (n = 50) were recruited from the Incidence of Cognitive Impairment in Cohorts with Lon

Baseline and longitudinal grey matter changes in newly diagnosed Parkinson's disease : ICICLE-PD study

Mild cognitive impairment in Parkinson's disease is associated with progression to dementia (Parkinson's disease dementia) in a majority of patients. Determining structural imaging biomarkers associated with prodromal Parkinson's disease dementia may allow for the earlier identification of those at risk, and allow for targeted disease modifying therapies. One hundred and five non-demented subjects

Gamma-tubulin coordinates nuclear envelope assembly around chromatin

The cytosolic role of γ-tubulin as a microtubule organizer has been studied thoroughly, but its nuclear function is poorly understood. Here, we show that γ-tubulin is located throughout the chromatin of demembranated Xenopus laevis sperm and, as the nucleus is formed, γ-tubulin recruits lamin B3 and nuclear membranes. Immunodepletion of γ-tubulin impairs X. laevis assembly of both the lamina and t