Utility of Huntington's Disease Assessments by Disease Stage: Floor/Ceiling Effects.

An understanding of the clinimetric properties of clinical assessments, including their constraints, is critical to sound clinical study and trial design. Utilizing data from Enroll-HD-a global, prospective HD observational study and clinical research platform-we examined several well-established HD clinical assessments across all stages of disease for evidence of instrument constraints, specifically floor/ceiling effects, to inform selection of appropriate instruments for use in future studies/trials and identify gaps in instrument utility over the life-course of the disease. Analyzing publicly available data from 6,614 HD gene-expansion carriers (HDGECs), we grouped participants into deciles based on baseline CAP score, which ranged from 26 to 229.

PET Molecular Imaging of Phosphodiesterase 10A: An Early Biomarker of Huntington's Disease Progression.

Background: Changes in phosphodiesterase 10A enzyme levels may be a suitable biomarker of disease progression in Huntington's disease.

Objectives: To evaluate phosphodiesterase 10A PET imaging as a biomarker of HD progression using the radioligand, [ F]MNI-659.

Methods: The cross-sectional study (NCT02061722) included 45 Huntington's disease gene-expansion carriers stratified into four disease stages (early and late premanifest and Huntington's disease stages 1 and 2) and 45 age- and sex-matched healthy controls.

Patterns of age related changes for phosphodiesterase type-10A in comparison with dopamine D receptors and sub-cortical volumes in the human basal ganglia: A PET study with F-MNI-659 and C-raclopride with correction for partial volume effect.

Phosphodiesterase 10A enzyme (PDE10A) is an important striatal target that has been shown to be affected in patients with neurodegenerative disorders, particularly Huntington´s disease (HD). PDE10A is expressed on striatal neurones in basal ganglia where other known molecular targets are enriched such as dopamine D receptors (D R). The aim of this study was to examine the availability of PDE10A enzyme in relation with age and gender and to compare those changes with those related to D R and volumes in different regions of the basal ganglia.

Long-term effects of rasagiline and the natural history of treated Parkinson's disease.

Background: The Attenuation of Disease progression with Azilect GIven Once-daily (ADAGIO) delayed-start study demonstrated a benefit of early-start treatment with rasagiline 1 mg/day versus delayed-start treatment in PD. This follow-up study aimed to assess whether these benefits persist and the clinical progression rate during long-term naturalistic treatment.

Methods: The ADAGIO Follow-Up study was initiated approximately 26 months after completion of the ADAGIO study.

Data Analytics from Enroll-HD, a Global Clinical Research Platform for Huntington's Disease.

Background: The study of complex neurodegenerative diseases is moving away from hypothesis-driven biological methods toward large scale multimodal approaches, requiring standardized collaborative efforts. Enroll-HD exemplifies such an integrated clinical research platform, designed and implemented to meet the research and clinical needs of Huntington's disease (HD). The aim of this study was to describe the unique organization of Enroll-HD and report baseline data analyses of its core study.

Efficacy of rasagiline in patients with the parkinsonian variant of multiple system atrophy: a randomised, placebo-controlled trial.

Background: Multiple system atrophy is a complex neurodegenerative disorder for which no effective treatment exists. We aimed to assess the effect of rasagiline on symptoms and progression of the parkinsonian variant of multiple system atrophy.

Methods: We did this randomised, double-blind, placebo-controlled trial between Dec 15, 2009, and Oct 20, 2011, at 40 academic sites specialised in the care of patients with multiple systemic atrophy across 12 countries.

A double-blind, delayed-start trial of rasagiline in Parkinson's disease (the ADAGIO study): prespecified and post-hoc analyses of the need for additional therapies, changes in UPDRS scores, and non-motor outcomes.

Background: The ADAGIO study investigated whether rasagiline has disease-modifying effects in Parkinson's disease. Rasagiline 1 mg per day, but not 2 mg per day, was shown to be efficacious in the primary analysis. Here, we report additional secondary and post-hoc analyses of the ADAGIO study.

Long-term efficacy of rasagiline in early Parkinson's disease.

This study was designed to follow the long-term efficacy, safety, and tolerability of rasagiline for Parkinson's disease (PD) with data collected from all patients who had ever taken rasagiline during the 12-month TEMPO monotherapy trial (N = 398) and subsequent open-label extension. Patients were followed for up to 6.5 years with a mean of 3.

Long-term outcome of early versus delayed rasagiline treatment in early Parkinson's disease.

The purpose of this study to compare the long-term clinical outcome of early versus delayed rasagiline treatment in early Parkinson's disease (PD). Subjects (N = 404) were randomly assigned to initial treatment with rasagiline (early-start group) or placebo for 6 months followed by rasagiline (delayed-start group) in the TEMPO study. Subjects who chose to participate in an open-label extension (N = 306) continued to receive rasagiline as well as other PD medications as needed.