Trial of Lixisenatide in Early Parkinson's Disease.

Background: Lixisenatide, a glucagon-like peptide-1 receptor agonist used for the treatment of diabetes, has shown neuroprotective properties in a mouse model of Parkinson's disease.

Methods: In this phase 2, double-blind, randomized, placebo-controlled trial, we assessed the effect of lixisenatide on the progression of motor disability in persons with Parkinson's disease. Participants in whom Parkinson's disease was diagnosed less than 3 years earlier, who were receiving a stable dose of medications to treat symptoms, and who did not have motor complications were randomly assigned in a 1:1 ratio to daily subcutaneous lixisenatide or placebo for 12 months, followed by a 2-month washout period.

Patient-perceived progression in multiple system atrophy: natural history of quality of life.

Background: Health-related quality of life (Hr-QoL) scales provide crucial information on neurodegenerative disease progression, help improve patient care and constitute a meaningful endpoint for therapeutic research. However, Hr-QoL progression is usually poorly documented, as for multiple system atrophy (MSA), a rare and rapidly progressing alpha-synucleinopathy. This work aimed to describe Hr-QoL progression during the natural course of MSA, explore disparities between patients and identify informative items using a four-step statistical strategy.

Care of Late-Stage Parkinsonism: Resource Utilization of the Disease in Five European Countries.

Background: Parkinson's disease (PD) is a neurodegenerative disease that leads to progressive disability. Cost studies have mainly explored the early stages of the disease, whereas late-stage patients are underrepresented.

Objective: The aim is to evaluate the resource utilization and costs of PD management in people with late-stage disease.

Progressive Brain Atrophy in Multiple System Atrophy: A Longitudinal, Multicenter, Magnetic Resonance Imaging Study.

Objective: To determine the rates of brain atrophy progression in vivo in patients with multiple system atrophy (MSA).

Background: Surrogate biomarkers of disease progression are a major unmet need in MSA. Small-scale longitudinal studies in patients with MSA using magnetic resonance imaging (MRI) to assess progression of brain atrophy have produced inconsistent results.

Retinal microvasculature and incident dementia over 10 years: The Three-City-Alienor cohort.

Introduction: We explored the longitudinal relationship between retinal vascular features and dementia incidence over 10 years.

Methods: Among 584 participants from the Three-City-Alienor (3C-Alienor) population-based cohort, quantitative retinal vascular features (caliber, tortuosity, fractal dimension) were measured using semi-automated software. Dementia was actively diagnosed over the follow-up period.

Describing complex disease progression using joint latent class models for multivariate longitudinal markers and clinical endpoints.

Neurodegenerative diseases are characterized by numerous markers of progression and clinical endpoints. For instance, multiple system atrophy (MSA), a rare neurodegenerative synucleinopathy, is characterized by various combinations of progressive autonomic failure and motor dysfunction, and a very poor prognosis. Describing the progression of such complex and multi-dimensional diseases is particularly difficult.

Alterations in electrochemical skin conductance as a marker of autonomic dysfunction in multiple system atrophy.

Background: Multiple System Atrophy (MSA) is a rare neurodegenerative disease with pronounced autonomic failure (AF). Severe cardiovascular AF is associated with poor prognosis. Since sweating dysfunction is less well known, we investigated the interest of a quick and non-invasive assessment of sweating using electrochemical skin conductance (ESC) as a marker for AF in MSA.

Neurofilament light levels predict clinical progression and death in multiple system atrophy.

Disease-modifying treatments are currently being trialled in multiple system atrophy. Approaches based solely on clinical measures are challenged by heterogeneity of phenotype and pathogenic complexity. Neurofilament light chain protein has been explored as a reliable biomarker in several neurodegenerative disorders but data on multiple system atrophy have been limited.

Joint models for the longitudinal analysis of measurement scales in the presence of informative dropout.

In health cohort studies, repeated measures of markers are often used to describe the natural history of a disease. Joint models allow to study their evolution by taking into account the possible informative dropout usually due to clinical events. However, joint modeling developments mostly focused on continuous Gaussian markers while, in an increasing number of studies, the actual quantity of interest is non-directly measurable; it constitutes a latent variable evaluated by a set of observed indicators from questionnaires or measurement scales.

Infectious Agents as Potential Drivers of α-Synucleinopathies.

α-synucleinopathies, encompassing Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, are devastating neurodegenerative diseases for which available therapeutic options are scarce, mostly because of our limited understanding of their pathophysiology. Although these pathologies are attributed to an intracellular accumulation of the α-synuclein protein in the nervous system with subsequent neuronal loss, the trigger(s) of this accumulation is/are not clearly identified. Among the existing hypotheses, interest in the hypothesis advocating the involvement of infectious agents in the onset of these diseases is renewed.

Ambulatory blood pressure and drug treatment for orthostatic hypotension as predictors of mortality in patients with multiple system atrophy.

Objectives: Multiple system atrophy (MSA) is a rare fatal neurodegenerative disease characterized by parkinsonism, cerebellar ataxia and autonomic failure. This study was aimed at investigating possible associations between mortality, 24-h blood pressure (BP) level and variability, and drug treatments for orthostatic hypotension (OH) in MSA patients.

Methods: A total of 129 patients followed at the French Reference Center for MSA who underwent routine 24-h ambulatory BP monitoring were included.

Diagnostic value of cerebrospinal fluid alpha-synuclein seed quantification in synucleinopathies.

Several studies have confirmed the α-synuclein real-time quaking-induced conversion (RT-QuIC) assay to have high sensitivity and specificity for Parkinson's disease. However, whether the assay can be used as a robust, quantitative measure to monitor disease progression, stratify different synucleinopathies and predict disease conversion in patients with idiopathic REM sleep behaviour disorder remains undetermined. The aim of this study was to assess the diagnostic value of CSF α-synuclein RT-QuIC quantitative parameters in regard to disease progression, stratification and conversion in synucleinopathies.

An Item Response Theory analysis of the Unified Multiple System Atrophy Rating Scale.

Introduction: The Unified Multiple System Atrophy Rating Scale (UMSARS) has four subscales that have been specifically designed for the clinical assessment of MSA patients. UMSARS I (activities of daily living) and II (motor examination) subscales are regularly used as primary endpoints in treatment trials. The main objective of this study was to identify UMSARS I and II subscale items that best describe progression over time.

A Biological Index to Screen Multi-Micronutrient Deficiencies Associated with the Risk to Develop Dementia in Older Persons from the Community.

Background: Low blood status in several nutritional compounds, including long-chain omega-3 fatty acids (LC n-3 PUFA), carotenoids, and vitamin D, have been associated with a higher risk to develop dementia. Nutritional deficiencies may potentiate each other regarding dementia risk; yet the association of multiple nutritional deficiencies with dementia has been little explored.

Objective: To develop an index of micronutritional biological status (MNBS) for the screening of multi-micronutritional deficiencies associated with the risk of dementia in a prospective population-based cohort of older persons.

Serum miR-96-5P and miR-339-5P Are Potential Biomarkers for Multiple System Atrophy and Parkinson's Disease.

Parkinson's disease (PD) and Multiple System Atrophy (MSA) are progressive neurodegenerative diseases with overlap of symptoms in early stages of disease. No reliable biomarker exists and the diagnosis is mainly based on clinical features. Several studies suggest that miRNAs are involved in PD and MSA pathogenesis.

Fluoxetine for the Symptomatic Treatment of Multiple System Atrophy: The MSA-FLUO Trial.

Background: There are no effective treatments for multiple system atrophy (MSA).

Objective: The objective of this study was to assess the efficacy and safety of the serotonin reuptake inhibitor fluoxetine (40 mg/d) for the symptomatic treatment of MSA.

Methods: This was a double-blind, parallel-group, placebo-controlled, randomized trial in patients with "probable" MSA.

Plasma carotenoids and medial temporal lobe atrophy in older adults.

Background & Aims: Carotenoids are vegetable pigments with neuroprotective properties. Clinical studies found efficacy of specific carotenoids on improving brain perfusion and functioning with aging. However, evidence of an effect on neurodegeneration, which may require longer follow-up period to observe, is more limited.