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Retrospective assessment of movement disorder society criteria for mild cognitive impairment in Parkinson's disease

A Movement Disorder Society (MDS) taskforce recently proposed diagnostic criteria for Parkinson's disease with features of mild cognitive impairment (PD-MCI). This study first examined the prevalence and nature of PD-MCI in a non-demented cohort using the MDS criteria. Using the generic Monte Carlo simulation method developed by Crawford and colleagues (2007), this study then estimated the base ra

The effect of multidisciplinary rehabilitation on brain structure and cognition in Huntington's disease : an exploratory study

BACKGROUND: There is a wealth of evidence detailing gray matter degeneration and loss of cognitive function over time in individuals with Huntington's disease (HD). Efforts to attenuate disease-related brain and cognitive changes have been unsuccessful to date. Multidisciplinary rehabilitation, comprising motor and cognitive intervention, has been shown to positively impact on functional capacity,

Association between MAPT haplotype and memory function in patients with Parkinson's disease and healthy aging individuals

Genetic variation is associated with differences in the function of the brain as well as its susceptibility to disease. The common H1 haplotypic variant of the microtubule-associated protein tau gene (MAPT) has been related to an increased risk for Parkinson's disease (PD). Furthermore, among PD patients, H1 homozygotes have an accelerated progression to dementia. We investigated the neurocognitiv

Developing stem cell therapies for Parkinson's disease : waiting until the time is right

The ability to successfully replace lost nigral dopaminergic neurons in Parkinson's disease (PD) has been clearly shown with fetal ventral mesencephalic transplants, albeit inconsistently. The need to trial this approach with stem-cell-derived neurons is approaching, but it should only commence when all the key issues have been adequately resolved.

Prediction of manifest Huntington's disease with clinical and imaging measures : a prospective observational study

BACKGROUND: Although the association between cytosine-adenine-guanine (CAG) repeat length and age at onset of Huntington's disease is well known, improved prediction of onset would be advantageous for clinical trial design and prognostic counselling. We compared various measures for tracking progression and predicting conversion to manifest Huntington's disease.METHODS: In this prospective observa

'The clocks that time us'--circadian rhythms in neurodegenerative disorders

Circadian rhythms are physiological and behavioural cycles generated by an endogenous biological clock, the suprachiasmatic nucleus. The circadian system influences the majority of physiological processes, including sleep-wake homeostasis. Impaired sleep and alertness are common symptoms of neurodegenerative disorders, and circadian dysfunction might exacerbate the disease process. The pathophysio

Molecular and functional definition of the developing human striatum

The complexity of the human brain derives from the intricate interplay of molecular instructions during development. Here we systematically investigated gene expression changes in the prenatal human striatum and cerebral cortex during development from post-conception weeks 2 to 20. We identified tissue-specific gene coexpression networks, differentially expressed genes and a minimal set of bimodal

Which patients with Parkinson's disease participate in clinical trials? : One centre's experiences with a new cell based therapy trial (TRANSEURO)

BACKGROUND: There is currently little evidence regarding the selection of patients for clinical trials in Parkinson's Disease (PD), especially those involving experimental therapies delivered using invasive techniques.OBJECTIVE: Understanding which patients are recruited will increase awareness of issues regarding parity of access to clinical trials and have an impact on the wider applicability of

Mild cognitive impairment and Parkinson's disease - something to remember

Cognitive impairment is common in Parkinson's disease (PD), and many patients will eventually develop a dementia, which has a devastating impact on the patient and their family. As such, there has been much interest in identifying a prodromal state to inform prognosis and facilitate earlier management, similar to the concept of 'MCI' in the Alzheimer's field. However, grouping the early cognitive

Modelling of a targeted nanotherapeutic 'stroma' to deliver the cytokine LIF, or XAV939, a potent inhibitor of Wnt-β-catenin signalling, for use in human fetal dopaminergic grafts in Parkinson's disease

The endogenous reparative capacity of the adult human brain is low, and chronic neurodegenerative disorders of the central nervous system represent one of the greatest areas of unmet clinical need in the developing world. Novel therapeutic strategies to treat them include: (i) growth factor delivery to boost endogenous repair and (ii) replacement cell therapy, including replacing dopaminergic neur

Genetic impact on cognition and brain function in newly diagnosed Parkinson's disease : ICICLE-PD study

Parkinson's disease is associated with multiple cognitive impairments and increased risk of dementia, but the extent of these deficits varies widely among patients. The ICICLE-PD study was established to define the characteristics and prevalence of cognitive change soon after diagnosis, in a representative cohort of patients, using a multimodal approach. Specifically, we tested the 'Dual Syndrome'

Targeting impulsivity in Parkinson's disease using atomoxetine

Noradrenergic dysfunction may play a significant role in cognition in Parkinson's disease due to the early degeneration of the locus coeruleus. Converging evidence from patient and animal studies points to the role of noradrenaline in dopaminergically insensitive aspects of the parkinsonian dysexecutive syndrome, yet the direct effects of noradrenergic enhancement have not to date been addressed.

Mutant huntingtin is present in neuronal grafts in Huntington disease patients

OBJECTIVE: Huntington disease (HD) is caused by a genetically encoded pathological protein (mutant huntingtin [mHtt]), which is thought to exert its effects in a cell-autonomous manner. Here, we tested the hypothesis that mHtt is capable of spreading within cerebral tissue by examining genetically unrelated fetal neural allografts within the brains of patients with advancing HD.METHODS: The presen

Theoretical Modeling of Water Exchange on [Pd(H2O)4]2+, [Pt(H2O)4]2+, and trans-[PtCl2(H2O)2]

SynopsisOptimized structures describing key features of the potential energy surface for water exchange at three planar d8 centers have been calculated using ab initio density functional theory. The local density approximation (LDA), including relativistic corrections for Pt, gives good agreement with the available experimental ground state structural data. LDA binding energies together with expli

Kinetics and Mechanism for Reduction of trans-Dichlorotetracyanoplatinate(IV) by Thioglycolic Acid, L-Cysteine, D,L-Penicillamine, and Glutathione in Aqueous Solution

SynopsisVarious protolytic species of thiols RSH (thioglycolic acid, l-cysteine, dl-penicillamine, and glutathione) in rapid equilibria with each other reduce trans-[Pt(CN)4Cl2]2- in parallel, halide-bridged electron transfer reactions. A linear Brønsted correlation between the reactivity of the thiolate anions RS- and their basicity is observed. The mechanism derived might be used as a model for

Competitive Substitution and Electron Transfer in Reactions between Haloamminegold(III) and Halocyanoaurate(III) Complexes and Thiocyanate

SynopsisReduction of gold(III) complexes by thiocyanate takes place via rapid substitutions at gold(III), followed by intramolecular, slower reductive elimination through attack by outer-sphere thiocyanate. A transition state with an S−S interaction between attacking and coordinated thiocyanate is suggested for the redox process.AbstractAbstract ImageKinetics for reactions between thiocyanate and SynopsisReduction of gold(III) complexes by thiocyanate takes place via rapid substitutions at gold(III), followed by intramolecular, slower reductive elimination through attack by outer-sphere thiocyanate. A transition state with an S−S interaction between attacking and coordinated thiocyanate is suggested for the redox process.AbstractAbstract ImageKinetics for reactions between thiocyanate and