Differential effects of Alzheimer\u27s disease and Huntington\u27s disease on the performance of mental rotation

he ability to spatially rotate a mental image was compared in patients with Alzheimer\u27s disease (AD; n = 18) and patients with Huntington\u27s disease (HD; n = 18). Compared to their respective age-matched normal control (NC) group, the speed, but not the accuracy, of mental rotation abnormally decreased with increasing angle of orientation for patients with HD. In contrast, the accuracy, but not the speed, of rotation abnormally decreased with increasing angle of orientation for patients with AD. Additional analyses showed that these unique patterns of performance were not attributable to different speed/accuracy trade-off sensitivities. This double dissociation suggests that the distinct brain regions affected in the two diseases differentially contribute to speed and accuracy of mental rotation. Specifically, the slowing exhibited by HD patients may be mediated by damage to the basal ganglia, whereas the spatial manipulation deficit of AD patients may reflect pathology in parietal and temporal lobe association cortices important for visuospatial processing. (JINS, 2005, 11, 30–39.

Measurement of T1 of the ultrashort T2* components in white matter of the brain at 3T.

Recent research demonstrates that white matter of the brain contains not only long T2 components, but a minority of ultrashort T2* components. Adiabatic inversion recovery prepared dual echo ultrashort echo time (IR-dUTE) sequences can be used to selectively image the ultrashort T2* components in white matter of the brain using a clinical whole body scanner. The T2*s of the ultrashort T2* components can be quantified using mono-exponential decay fitting of the IR-dUTE signal at a series of different TEs. However, accurate T1 measurement of the ultrashort T2* components is technically challenging. Efficient suppression of the signal from the majority of long T2 components is essential for robust T1 measurement. In this paper we describe a novel approach to this problem based on the use of IR-dUTE data acquisitions with different TR and TI combinations to selectively detect the signal recovery of the ultrashort T2* components. Exponential recovery curve fitting provides efficient T1 estimation, with minimized contamination from the majority of long T2 components. A rubber phantom and a piece of bovine cortical bone were used for validation of this approach. Six healthy volunteers were studied. An averaged T2* of 0.32 ± 0.09 ms, and a short mean T1 of 226 ± 46 ms were demonstrated for the healthy volunteers at 3T

Uric Acid as a Potential Peripheral Biomarker for Disease Features in Huntington's Patients.

Oxidative stress has long been implicated in the pathophysiology and progression of Huntington's disease (HD). Uric acid (UA) is a naturally occurring antioxidant that is present in the brain and periphery. Growing evidence has implicated UA as a molecular biomarker for several neurodegenerative diseases, most notably Parkinson's disease (PD). In this study, we investigated UA levels in clinical samples from HD patients and normal controls (NCs) and assessed potential relationships between UA levels and disease and clinical data. UA levels were measured in plasma (n = 107) and saliva (n = 178) samples from premanifest (pre-HD) and manifest HD patients and control subjects. Gender effects of UA levels were observed in both biofluids, with male patients showing higher UA levels compared to female patients. Comparisons of UA levels across diagnostic groups, separated by gender, revealed that both plasma and salivary UA levels were significantly lower in female pre-HD and manifest HD patients compared to NCs. Salivary levels of UA were also significantly lower in male manifest HD patients versus controls, but not in plasma. Correlations of peripheral UA levels to clinical data also showed differences according to gender. In male HD patients, both plasma and salivary UA levels were significantly negatively correlated with total functional capacity (TFC), while positive correlations were observed with total motor score (TMS). Female HD patients showed a significant positive correlation between plasma UA levels and TMS, while salivary UA levels from female patients were significantly correlated to disease burden. Finally, in a separate cohort, we show that UA levels are decreased in postmortem prefrontal cortical samples (n = 20) from HD subjects compared to matched controls. These findings suggest that decreased levels of UA in the brains of HD patients can be reflected in peripheral fluids, with salivary measures of UA particularly offering significant promise as a potentially relevant, non-invasive biomarker of disease symptoms and burden. Our findings further highlight the impact of sexual dimorphism in HD pathophysiology

Pharmacokinetics of a novel transdermal rivastigmine patch for the treatment of Alzheimer’s disease: a review

Cholinesterase inhibitors have all been available in oral formulations, but a rivastigmine transdermal patch has now been developed and is approved in many countries worldwide for the treatment of mild-to-moderate Alzheimer's disease (AD) (including the USA, Latin America, Europe and Asia)

EXACT: rivastigmine improves the high prevalence of attention deficits and mood and behaviour symptoms in Alzheimer's disease*

The objective of this study was to investigate the impact of rivastigmine therapy on attention, apathy, anxiety and agitation in patients with mild-to-moderate Alzheimer's disease (AD) in a real-world clinical setting. Patients with mild-to-moderate AD were enrolled in the study by physicians across Canada. They were treated with open-label rivastigmine (dose at the discretion of the prescribing physicians) for a period of 6 months. Changes from baseline in attention, apathy, anxiety and agitation were assessed using an abbreviated Clinician's Global Impression of Change at 3- and 6-month visits. The Mini Mental State Examination (MMSE) was also used at these visits. Use and changes in use of psychotropic medications were recorded, as were changes in caregiver burden. Analyses of subgroups (outpatients vs. institutionalised patients) were also performed. A total of 2119 patients were enrolled in the study by 375 physicians. At baseline, 91% had deficits in attention, 85.4% had symptoms of anxiety, 78.5% exhibited apathy and 70.1% showed agitation. At 6 months, 67.5% of evaluable patients had improved on the symptom of attention, while 62.3%, 62.6% and 56.0% had improvements in anxiety, apathy and agitation respectively. The percentages with improvements were higher in the institutional subgroup than among outpatients. There was an overall mean improvement of 1.1 points on the MMSE at 6 months. Approximately four times as many caregivers reported a reduced burden than an increased burden at 6 months (40.3% vs. 10.3%). The majority of patients treated with rivastigmine experienced improvements in attention, anxiety, apathy and agitation. These real-life findings further demonstrate the proven efficacy of rivastigmine in patients with mild-to-moderate AD

RIPOSTE: a framework for improving the design and analysis of laboratory-based research.

Lack of reproducibility is an ongoing problem in some areas of the biomedical sciences. Poor experimental design and a failure to engage with experienced statisticians at key stages in the design and analysis of experiments are two factors that contribute to this problem. The RIPOSTE (Reducing IrreProducibility in labOratory STudiEs) framework has been developed to support early and regular discussions between scientists and statisticians in order to improve the design, conduct and analysis of laboratory studies and, therefore, to reduce irreproducibility. This framework is intended for use during the early stages of a research project, when specific questions or hypotheses are proposed. The essential points within the framework are explained and illustrated using three examples (a medical equipment test, a macrophage study and a gene expression study). Sound study design minimises the possibility of bias being introduced into experiments and leads to higher quality research with more reproducible results

Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

PMCID: PMC379391

Rivastigmine: an open-label, observational study of safety and effectiveness in treating patients with Alzheimer's disease for up to 5 years

BACKGROUND: Rivastigmine, a butyl- and acetylcholinesterase inhibitor, is approved for symptomatic treatment of Alzheimer's disease (AD). Data supporting the safety and efficacy of second-generation cholinesterase inhibitors, such as rivastigmine, are available for treatment up to 1 year, with limited data up to 2 1/2 years. The purpose of this report is to present safety and effectiveness data for rivastigmine therapy in patients with mild to moderately severe AD receiving treatment for up to 5 years. METHODS: An observational approach was used to study 37 patients with originally mild to moderate AD receiving rivastigmine as a therapy for AD in an open-label extension (ENA713, B352 Study Group, 1998). RESULTS: The initial trial demonstrated rivastigmine was well-tolerated and effective in terms of cognition, global functioning and activities of daily living. In this open label extension, high-dose rivastigmine therapy was safe and well tolerated over a 5-year period. Two thirds of the participants still enrolled at week 234 were in the original high-dose rivastigmine group during the double-blind phase, suggesting that early therapy may confer some benefit in delaying long-term progression of symptoms. CONCLUSIONS: Long-term cholinesterase inhibition therapy with rivastigmine was well tolerated, with no dropouts due to adverse effects past the initial titration period. Early initiation of treatment, with titration to high-dose therapy, may have an advantage in delaying progression of the illness

Direct Decarboxylative Allylation and Arylation of Aliphatic Carboxylic Acids Using Flavin‐Mediated Photoredox Catalysis

We describe herein a direct decarboxylative allylation of aliphatic carboxylic acids with allylsulfones using visible light and riboflavin tetraacetate (RFTA) as photocatalyst. The reaction proceeds at room temperature tolerating a wide range of functionalities, avoiding the use of external bases or additives. Mechanistic studies support that alkyl radicals are involved in the reaction and that a true photocatalytic cycle is operating. It is proposed that the carboxylic acid is deprotonated by [RFTA]·–, and the corresponding carboxylate acts as a reductive quencher of RFTA*, which after decarboxylation produces the alkyl radical. The methodology was adapted to prepare benzothiazoles substituted at C2, by reacting some carboxylic acids with 2‐(phenylsulfonyl)benzothiazole. The number of carboxylic acids suitable for this arylation was lower than for the allylation and this different reactivity was briefly commented.This work was generously supported by the Spanish Ministerio de Economía y Competitividad (CTQ2017–88171-P) and the Generalitat Valenciana (AICO/2017/007). N. P. R. thanks to Instituto de Síntesis Orgánica for financial support