Plasma and cerebrospinal fluid pharmacokinetics of vodobatinib, a neuroprotective c-Abl tyrosine kinase inhibitor for the treatment of Parkinson's disease.

Background: Preclinical evidence suggests that c-Abl is critical in the pathogenesis of Parkinson's Disease (PD). Vodobatinib (K0706) is a potent, specific Abl kinase inhibitor currently being developed for the treatment of PD. In previously reported studies, nilotinib, a multikinase c-Abl inhibitor, did not show clinical activity as evidenced by no improvement of symptoms or the rate of decline after one to six months of treatment at the maximum permissible dose, presumably because of insufficient CNS penetration.

Analysis of Brain Structural Connectivity Networks and White Matter Integrity in Patients With Mild Cognitive Impairment.

White matter integrity and structural connectivity may be altered in mild cognitive impairment (MCI), and these changes may closely reflect decline in specific cognitive domains. Multi-shell diffusion data in healthy control (HC, = 31) and mild cognitive impairment (MCI, = 19) cohorts were downloaded from the ADNI3 database. The data were analyzed using an advanced approach to assess both white matter microstructural integrity and structural connectivity.

Sex Differences in Alzheimer's Disease Revealed by Free-Water Diffusion Tensor Imaging and Voxel-Based Morphometry.

Background: Imaging biomarkers are increasingly used in Alzheimer's disease (AD), and the identification of sex differences using neuroimaging may provide insight into disease heterogeneity, progression, and therapeutic targets.

Objective: The purpose of this study was to investigate differences in grey matter (GM) volume and white matter (WM) microstructural disorganization between males and females with AD using voxel-based morphometry (VBM) and free-water-corrected diffusion tensor imaging (FW-DTI).

Methods: Data were downloaded from the OASIS-3 database, including 158 healthy control (HC; 86 females) and 46 mild AD subjects (24 females).

Energy-Period Profiles of Brain Networks in Group fMRI Resting-State Data: A Comparison of Empirical Mode Decomposition With the Short-Time Fourier Transform and the Discrete Wavelet Transform.

Traditionally, functional networks in resting-state data were investigated with linear Fourier and wavelet-related methods to characterize their frequency content by relying on pre-specified frequency bands. In this study, Empirical Mode Decomposition (EMD), an adaptive time-frequency method, is used to investigate the naturally occurring frequency bands of resting-state data obtained by Group Independent Component Analysis. Specifically, energy-period profiles of Intrinsic Mode Functions (IMFs) obtained by EMD are created and compared for different resting-state networks.

Amantadine ER (Gocovri) Significantly Increases ON Time Without Any Dyskinesia: Pooled Analyses From Pivotal Trials in Parkinson's Disease.

Clinical trials for antiparkinsonian drugs aimed at managing motor complications typically use patient diaries to divide levodopa-induced dyskinesias (LID) into "troublesome" and "non-troublesome" categories. Yet, given the choice, most patients would prefer to live without experiencing any dyskinesia. However, the concept of evaluating time spent ON any dyskinesia as an outcome has never been tested.

Free-water diffusion tensor imaging improves the accuracy and sensitivity of white matter analysis in Alzheimer's disease.

Magnetic resonance imaging (MRI) based diffusion tensor imaging (DTI) can assess white matter (WM) integrity through several metrics, such as fractional anisotropy (FA), axial/radial diffusivities (AxD/RD), and mode of anisotropy (MA). Standard DTI is susceptible to the effects of extracellular free water (FW), which can be removed using an advanced free-water DTI (FW-DTI) model. The purpose of this study was to compare standard and FW-DTI metrics in the context of Alzheimer's disease (AD).

Systematic Assessment of the Impact of DTI Methodology on Fractional Anisotropy Measures in Alzheimer's Disease.

White matter microstructural changes in Alzheimer's disease (AD) are often assessed using fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI). FA depends on the acquisition and analysis methods, including the fitting algorithm. In this study, we compared FA maps from different acquisitions and fitting algorithms in AD, mild cognitive impairment (MCI), and healthy controls (HCs) using the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.

Central airway collapse is related to obesity independent of asthma phenotype.

Background And Objective: Late-onset non-allergic asthma in obesity is characterized by an abnormally compliant, collapsible lung periphery; it is not known whether this abnormality exists in proximal airways. We sought to compare collapsibility of central airways between lean and obese individuals with and without asthma.

Methods: A cross-sectional study comparing luminal area and shape (circularity) of the trachea, left mainstem bronchus, right bronchus intermedius and right inferior lobar bronchus at RV and TLC by CT was conducted.

Preliminary Assessment of Intravoxel Incoherent Motion Diffusion-Weighted MRI (IVIM-DWI) Metrics in Alzheimer's Disease.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease that affects aging populations. Current MRI techniques are often limited in their sensitivity to underlying neuropathological changes.

Purpose: To characterize differences in voxel-based morphometry (VBM), apparent diffusion coefficient (ADC), and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) metrics in aging populations.

Assessing White Matter Pathology in Early-Stage Parkinson Disease Using Diffusion MRI: A Systematic Review.

Structural brain white matter (WM) changes such as axonal caliber, density, myelination, and orientation, along with WM-dependent structural connectivity, may be impacted early in Parkinson disease (PD). Diffusion magnetic resonance imaging (dMRI) has been used extensively to understand such pathological WM changes, and the focus of this systematic review is to understand both the methods utilized and their corresponding results in the context of early-stage PD. Diffusion tensor imaging (DTI) is the most commonly utilized method to probe WM pathological changes.

Unique white matter structural connectivity in early-stage drug-naive Parkinson disease.

Objective: To investigate the topographic arrangement and strength of whole-brain white matter (WM) structural connectivity in patients with early-stage drug-naive Parkinson disease (PD).

Methods: We employed a model-free data-driven approach for computing whole-brain WM topologic arrangement and connectivity strength between brain regions by utilizing diffusion MRI of 70 participants with early-stage drug-naive PD and 41 healthy controls. Subsequently, we generated a novel group-specific WM anatomical network by minimizing variance in anatomical connectivity of each group.

Prevalence of Dyskinesia and OFF by 30-Minute Intervals Through the Day and Assessment of Daily Episodes of Dyskinesia and OFF: Novel Analyses of Diary Data from Gocovri Pivotal Trials.

Background: Parkinson's disease (PD) patients using levodopa commonly develop dyskinesia and OFF episodes that reduce quality of life.

Objective: Evaluate prevalence of troublesome dyskinesia and OFF through the day, assessed by 30-minute intervals, as well as the mean number and duration of troublesome dyskinesia and OFF episodes, transitions between PD states, and effects of Gocovri® (amantadine) extended release capsules on these episodes.

Methods: Evaluate diary data from pooled Gocovri phase 3, placebo-controlled trials-analyzed for 17 hours following wake-up-at baseline and week 12.

Influence of analytic techniques on comparing DTI-derived measurements in early stage Parkinson's disease.

Diffusion tensor imaging (DTI) studies in early Parkinson's disease (PD) to understand pathologic changes in white matter (WM) organization are variable in their findings. Evaluation of different analytic techniques frequently employed to understand the DTI-derived change in WM organization in a multisite, well-characterized, early stage PD cohort should aid the identification of the most robust analytic techniques to be used to investigate WM pathology in this disease, an important unmet need in the field. Thus, region of interest (ROI)-based analysis, voxel-based morphometry (VBM) analysis with varying spatial smoothing, and the two most widely used skeletonwise approaches (tract-based spatial statistics, TBSS, and tensor-based registration, DTI-TK) were evaluated in a DTI dataset of early PD and Healthy Controls (HC) from the Parkinson's Progression Markers Initiative (PPMI) cohort.

Altered functional network topology correlates with clinical measures in very early-stage, drug-naïve Parkinson's disease.

Introduction: The aim of the study was to identify abnormalities of whole-brain network functional organization and their relation to clinical measures in a well-characterized, multi-site cohort of very early-stage, drug-naïve Parkinson's Disease (PD) patients.

Methods: Functional-MRI data for 16 healthy controls and 20 very early-stage, drug-naïve patients with PD were obtained from the Parkinson's Progression Markers Initiative database after controlling for strict inclusion/exclusion imaging criteria. Connectivity between regions of interest was estimated using Pearson's correlation between averaged time-series, and subsequently a connectivity matrix was obtained for each subject.

Incorporating spatial constraint in co-activation pattern analysis to explore the dynamics of resting-state networks: An application to Parkinson's disease.

The dynamics of the brain's intrinsic networks have been recently studied using co-activation pattern (CAP) analysis. The CAP method relies on few model assumptions and CAP-based measurements provide quantitative information of network temporal dynamics. One limitation of existing CAP-related methods is that the computed CAPs share considerable spatial overlap that may or may not be functionally distinct relative to specific network dynamics.

Recommendations of the Global Multiple System Atrophy Research Roadmap Meeting.

Multiple system atrophy (MSA) is a rare neurodegenerative disorder with substantial knowledge gaps despite recent gains in basic and clinical research. In order to make further advances, concerted international collaboration is vital. In 2014, an international meeting involving leaders in the field and MSA advocacy groups was convened in Las Vegas, Nevada, to identify critical research areas where consensus and progress was needed to improve understanding, diagnosis, and treatment of the disease.

Biomarkers of Cognitive Impairment: Brain Cortical Thickness, Volumetrics, and Cerebrospinal Fluid.

In Alzheimer’s disease (AD), association of cognition with disease biomarkers is important for accurate diagnosis, prognosis and staging. We studied the value of cerebrospinal fluid (CSF), cortical thickness (CT), and volume (V) measures (in isolation & combination) to predict cognitive ability, as well as cognitive status, in a cross-sectional study of data from Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cognitive status was measured by Mini Mental State Exam (MMSE).

Latent Cognitive Phenotypes in De Novo Parkinson's Disease: A Person-Centered Approach.

Objectives: Cognitive impairment is an important aspect of Parkinson's disease (PD), but there is considerable heterogeneity in its presentation. This investigation aims to identify and characterize latent cognitive phenotypes in early PD.

Methods: Latent class analysis, a data-driven, person-centered, cluster analysis was performed on cognitive data from the Parkinson's Progressive Markers Initiative baseline visit.

How Common Is Airflow Limitation in Patients With Emphysema on CT Scan of the Chest?

Background: COPD has traditionally been defined by the presence of irreversible airflow limitation on spirometry using either the GOLD (Global Initiative for Chronic Obstructive Lung Disease) or American Thoracic Society/European Respiratory Society criteria (lower limit of normal [LLN]). We have observed that some patients with clinical COPD and emphysema on chest CT scan have no obstruction on spirometry. The purpose of this study was to assess the prevalence of obstruction by GOLD and LLN criteria in patients with emphysema on CT scan and determine which radiographic criteria were associated with a clinical diagnosis of COPD.

Alzheimer's disease drug development: translational neuroscience strategies.

Alzheimer's disease (AD) is an urgent public health challenge that is rapidly approaching epidemic proportions. New therapies that defer or prevent the onset, delay the decline, or improve the symptoms are urgently needed. All phase 3 drug development programs for disease-modifying agents have failed thus far.