551 research outputs found
Tau protein, A beta 42 and S-100B protein in cerebrospinal fluid of patients with dementia with Lewy bodies
The intra vitam diagnosis of dementia with Lewy bodies (DLB) is still based on clinical grounds. So far no technical investigations have been available to support this diagnosis. As for tau protein and beta-amyloid((1-42)) (Abeta42), promising results for the diagnosis of Alzheimer's disease ( AD) have been reported; we evaluated these markers and S-100B protein in cerebrospinal fluid (CSF), using a set of commercially available assays, of 71 patients with DLB, 67 patients with AD and 41 nondemented controls (NDC) for their differential diagnostic relevance. Patients with DLB showed significantly lower tau protein values compared to AD but with a high overlap of values. More prominent differences were observed in the comparison of DLB patients with all three clinical core features and AD patients. Abeta42 levels were decreased in the DLB and AD groups versus NDC, without significant subgroup differences. S-100B levels were not significantly different between the groups. Tau protein levels in CSF may contribute to the clinical distinction between DLB and AD, but the value of the markers is still limited especially due to mixed pathology. We conclude that more specific markers have to be established for the differentiation of these diseases. Copyright (C) 2005 S. Karger AG, Basel
SCRN1: A cerebrospinal fluid biomarker correlating with tau in Alzheimer's disease
INTRODUCTION:
Secernin-1 (SCRN1) is a neuronal protein that co-localizes with neurofibrillary tangles in Alzheimer's disease (AD), but not with tau inclusions in corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), or Pick's disease.
METHODS:
We measured SCRN1 concentration in cerebrospinal fluid (CSF) using a novel mass spectrometric parallel reaction monitoring method in three clinical cohorts comprising patients with neurochemically characterized AD (n = 25) and controls (n = 28), clinically diagnosed Parkinson's disease (PD; n = 38), multiple system atrophy (MSA; n = 31), PSP (n = 20), CBD (n = 8), healthy controls (n = 37), and neuropathology-confirmed AD (n = 47).
RESULTS:
CSF SCRN1 was significantly increased in AD (P < 0.01, fold change = 1.4) compared to controls (receiver operating characteristic area under the curve = 0.78) but not in CBD, PSP, PD, or MSA. CSF SCRN1 positively correlated with CSF total tau (R = 0.78, P = 1.1 × 10−13), phosphorylated tau181 (R = 0.64, P = 3.2 × 10−8), and Braak stage and negatively correlated with Mini-Mental State Examination score.
DISCUSSION:
CSF SCRN1 is a candidate biomarker of AD, reflecting tau pathology
Managing Injuries of the Neck Trial (MINT) : design of a randomised controlled trial of treatments for whiplash associated disorders
Background: A substantial proportion of patients with whiplash injuries develop chronic
symptoms. However, the best treatment of acute injuries to prevent long-term problems is
uncertain. A stepped care treatment pathway has been proposed, in which patients are given advice
and education at their initial visit to the emergency department (ED), followed by review at three
weeks and physiotherapy for those with persisting symptoms. MINT is a two-stage randomised
controlled trial to evaluate two components of such a pathway: 1. use of The Whiplash Book versus
usual advice when patients first attend the emergency department; 2. referral to physiotherapy
versus reinforcement of advice for patients with continuing symptoms at three weeks.
Methods: Evaluation of the Whiplash Book versus usual advice uses a cluster randomised design
in emergency departments of eight NHS Trusts. Eligible patients are identified by clinicians in
participating emergency departments and are sent a study questionnaire within a week of their ED
attendance. Three thousand participants will be included. Patients with persisting symptoms three
weeks after their ED attendance are eligible to join an individually randomised study of
physiotherapy versus reinforcement of the advice given in ED. Six hundred participants will be
randomised. Follow-up is at 4, 8 and 12 months after their ED attendance. Primary outcome is the
Neck Disability Index (NDI), and secondary outcomes include quality of life and time to return to
work and normal activities. An economic evaluation is being carried out.
Conclusion: This paper describes the protocol and operational aspects of a complex intervention
trial based in NHS emergency and physiotherapy departments, evaluating two components of a
stepped-care approach to the treatment of whiplash injuries. The trial uses two randomisations,
with the first stage being cluster randomised and the second individually randomised
An open cohort study of bone metastasis incidence following surgery in breast cancer patients
Background: To help design clinical trials of adjuvant bisphosphonate therapy for breast cancer, the temporal incidence of bone metastasis was investigated in a cohort of patients. We have tried to draw the criteria to use adjuvant bisphosphonate.Methods: Consecutive breast cancer patients undergoing surgery between 1988 and 1998 (5459 patients) were followed up regarding bone metastasis until December 2006. Patients characteristics at the time of surgery were analyzed by Cox method, with bone metastasis as events. Patient groups were assigned according to Cox analysis, and were judged either to require the adjuvant bisphosphonate or not, using the tentative criteria: high risk (>3% person-year), medium risk (1-3%), and low risk (3% per person-year, patients with stage I <1% per person-year, andthose with stages II were between 1 and 3%. Further analysis with histology in stage II patients showed that stage IIB with high risk histology also had a high incidence (3% person year), whereas stage IIA with medium risk histology were <1%.Conclusions: Bone metastasis incidence remained constant for many years. Using pN, T, and histopathology, patients could be classified into high, medium, and low risk groups
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Lewy Body Dementia Association\u27s Research Centers of Excellence Program: Inaugural Meeting Proceedings.
The first Lewy Body Dementia Association (LBDA) Research Centers of Excellence (RCOE) Investigator\u27s meeting was held on December 14, 2017, in New Orleans. The program was established to increase patient access to clinical experts on Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson\u27s disease dementia (PDD), and to create a clinical trials-ready network. Four working groups (WG) were created to pursue the LBDA RCOE aims: (1) increase access to high-quality clinical care, (2) increase access to support for people living with LBD and their caregivers, (3) increase knowledge of LBD among medical and allied (or other) professionals, and (4) create infrastructure for a clinical trials-ready network as well as resources to advance the study of new therapeutics
Functional response to cholinesterase inhibitor therapy in a naturalistic Alzheimer’s disease cohort
Comparison of Pittsburgh compound B and florbetapir in cross-sectional and longitudinal studies.
IntroductionQuantitative in vivo measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of Pittsburgh compound B-based and florbetapir-based amyloid imaging in the same participants from two independent cohorts using a crossover design.MethodsPittsburgh compound B and florbetapir amyloid PET imaging data from three different cohorts were analyzed using previously established pipelines to obtain global amyloid burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison between the two tracers. The mean and inter-individual variability of the two tracers were compared using multivariate linear models both cross-sectionally and longitudinally.ResultsGlobal amyloid burden measured using the two tracers were strongly correlated in both cohorts. However, higher variability was observed when florbetapir was used as the imaging tracer. The variability may be partially caused by white matter signal as partial volume correction reduces the variability and improves the correlations between the two tracers. Amyloid burden measured using both tracers was found to be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar but separate cohorts whose baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers.DiscussionAlthough the amyloid burden measurements were quite similar using these two tracers as expected, difference was observable even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers
Lewy Body Dementia Association\u27s Research Centers of Excellence Program: Inaugural Meeting Proceedings
The first Lewy Body Dementia Association (LBDA) Research Centers of Excellence (RCOE) Investigator\u27s meeting was held on December 14, 2017, in New Orleans. The program was established to increase patient access to clinical experts on Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson\u27s disease dementia (PDD), and to create a clinical trials-ready network. Four working groups (WG) were created to pursue the LBDA RCOE aims: (1) increase access to high-quality clinical care, (2) increase access to support for people living with LBD and their caregivers, (3) increase knowledge of LBD among medical and allied (or other) professionals, and (4) create infrastructure for a clinical trials-ready network as well as resources to advance the study of new therapeutics
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Challenges and opportunities for improving the landscape for Lewy body dementia clinical trials.
Lewy body dementia (LBD), including dementia with Lewy bodies and Parkinson\u27s disease dementia, affects over a million people in the USA and has a substantial impact on patients, caregivers, and society. Symptomatic treatments for LBD, which can include cognitive, neuropsychiatric, autonomic, sleep, and motor features, are limited with only two drugs (cholinesterase inhibitors) currently approved by regulatory agencies for dementia in LBD. Clinical trials represent a top research priority, but there are many challenges in the development and implementation of trials in LBD. To address these issues and advance the field of clinical trials in the LBDs, the Lewy Body Dementia Association formed an Industry Advisory Council (LBDA IAC), in addition to its Research Center of Excellence program. The LBDA IAC comprises a diverse and collaborative group of experts from academic medical centers, pharmaceutical industries, and the patient advocacy foundation. The inaugural LBDA IAC meeting, held in June 2019, aimed to bring together this group, along with representatives from regulatory agencies, to address the topic of optimizing the landscape of LBD clinical trials. This review highlights the formation of the LBDA IAC, current state of LBD clinical trials, and challenges and opportunities in the field regarding trial design, study populations, diagnostic criteria, and biomarker utilization. Current gaps include a lack of standardized clinical assessment tools and evidence-based management strategies for LBD as well as difficulty and controversy in diagnosing LBD. Challenges in LBD clinical trials include the heterogeneity of LBD pathology and symptomatology, limited understanding of the trajectory of LBD cognitive and core features, absence of LBD-specific outcome measures, and lack of established standardized biologic, imaging, or genetic biomarkers that may inform study design. Demands of study participation (e.g., travel, duration, and frequency of study visits) may also pose challenges and impact trial enrollment, retention, and outcomes. There are opportunities to improve the landscape of LBD clinical trials by harmonizing clinical assessments and biomarkers across cohorts and research studies, developing and validating outcome measures in LBD, engaging the patient community to assess research needs and priorities, and incorporating biomarker and genotype profiling in study design
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