Disentangling time series between brain tissues improves fMRI data quality using a time-dependent deep neural network.

Functional MRI (fMRI) is a prominent imaging technique to probe brain function, however, a substantial proportion of noise from multiple sources influences the reliability and reproducibility of fMRI data analysis and limits its clinical applications. Extensive effort has been devoted to improving fMRI data quality, but in the last two decades, there is no consensus reached which technique is more effective. In this study, we developed a novel deep neural network for denoising fMRI data, named denoising neural network (DeNN).

Harnessing Real-World Data to Inform Decision-Making: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS).

Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is the first example of a learning health system in multiple sclerosis (MS). This paper describes the initial implementation of MS PATHS and initial patient characteristics. MS PATHS is an ongoing initiative conducted in 10 healthcare institutions in three countries, each contributing standardized information acquired during routine care.

Global Survey on Telemedicine Utilization for Movement Disorders During the COVID-19 Pandemic.

Background: The COVID-19 pandemic restricted usual healthcare management for movement-disorders patients, with a consequent upsurge in telemedicine to bridge the gap.

Objective: To assess global telemedicine usage in the context of the pandemic.

Methods: The Movement Disorder Society (MDS) Telemedicine Study Group surveyed telemedicine experts from 40 countries across all continents in March-April 2020.

The Role of Neuropsychiatric Symptoms in Research Diagnostic Criteria for Neurodegenerative Diseases.

Neuropsychiatric syndromes and symptoms play increasingly important roles in research diagnostic criteria for neurodegenerative disorders. Diagnostic criteria were reviewed including those for dementia, Alzheimer's disease, mild cognitive impairment, mild behavioral impairment, prodromal Alzheimer's disease, dementia with Lewy bodies, prodromal dementia with Lewy bodies, Parkinson's disease, multiple system atrophy, frontotemporal dementia, primary progressive aphasia, progressive supranuclear palsy, corticobasal degeneration, traumatic encephalopathy syndrome, Huntington' disease, amyotrophic lateral sclerorsis. All contemporary research diagnostic criteria for neurodegenerative disorders expect those for Parkinson's disease, primary progressive aphasia, multisystem atrophy and amyotrophic lateral sclerosis include neuropsychiatric phenomena as core diagnostic criteria.

Repurposed agents in the Alzheimer's disease drug development pipeline.

Background: Treatments are needed to address the growing prevalence of Alzheimer's disease (AD). Clinical trials have failed to produce any AD drugs for Food and Drug Administration (FDA) approval since 2003, and the pharmaceutical development process is both time-consuming and costly. Drug repurposing provides an opportunity to accelerate this process by investigating the AD-related effects of agents approved for other indications.

History of Chronic Traumatic Encephalopathy.

The long-term effects of repetitive head impacts have been recognized for close to a century. What is now referred to as chronic traumatic encephalopathy (CTE) was first described by Martland in 1928 in a series of boxers. Over the years, several important articles were published, including Critchley's 1957 report where he introduced the term "chronic traumatic encephalopathy," Robert's study in 1969 which provided evidence of the prevalence of neurological impairment in retired fighters, and Corsellis' initial description of the pathology of CTE.

Alzheimer's disease drug development pipeline: 2020.

Introduction: Alzheimer's disease (AD) is a growing public health concern affecting millions of patients worldwide and costing billions of dollars annually. We review the pipeline of drugs and biologics in clinical trials for the treatment of AD. We use the Common Alzheimer's and Related Dementias Research Ontology (CADRO) to classify treatment targets and mechanisms of action.

Re-Evaluating the Use of IFN-β and Relapsing Multiple Sclerosis: Safety, Efficacy and Place in Therapy.

The advent of interferon therapy for the treatment of multiple sclerosis (MS) was a massive advancement in the field and changed the course of the disease. While the exact mechanism of interferon therapy in MS is unknown, disease control is likely mediated by reducing Th1 and Th17 cells while increasing regulatory T cells and altering the cytokine profile. Interferon therapy not only gave physicians and patients an evidence-based treatment option to treat MS by decreasing relapses and the accrual of disability but it also provided valuable insight into disease pathophysiology that allowed for the development of further treatments.

Single-scale time-dependent window-sizes in sliding-window dynamic functional connectivity analysis: A validation study.

During the past ten years, dynamic functional connectivity (FC) has been extensively studied using the sliding-window method. A fixed window-size is usually selected heuristically, since no consensus exists yet on choice of the optimal window-size. Furthermore, without a known ground-truth, the validity of the computed dynamic FC remains unclear and questionable.

A technical review of canonical correlation analysis for neuroscience applications.

Collecting comprehensive data sets of the same subject has become a standard in neuroscience research and uncovering multivariate relationships among collected data sets have gained significant attentions in recent years. Canonical correlation analysis (CCA) is one of the powerful multivariate tools to jointly investigate relationships among multiple data sets, which can uncover disease or environmental effects in various modalities simultaneously and characterize changes during development, aging, and disease progressions comprehensively. In the past 10 years, despite an increasing number of studies have utilized CCA in multivariate analysis, simple conventional CCA dominates these applications.

Outcomes and future directions for neuroimmunology/multiple sclerosis fellowship training: Survey of recent trainees.

Background: Neuroimmunology/multiple sclerosis is a rapidly evolving, but still poorly defined subspecialty. Fellowship training is not standardized, and there is substantial variability across sites. Outcomes of fellowship training have not yet been studied.

Erratum: Author Correction: Report from a multidisciplinary meeting on anxiety as a non-motor manifestation of Parkinson's disease.

[This corrects the article DOI: 10.1038/s41531-019-0102-8.].

Translational Scoring of Candidate Treatments for Alzheimer's Disease: A Systematic Approach.

Background: There are many failures in treatment development for Alzheimer's disease (AD). Some of these failures are the result of development programs that lacked critical information about candidate drugs as these were advanced from one phase of development to the next. Translational scoring (TS) has been proposed as a means of increasing the rigor with which treatment development programs are executed.

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.

CAST: A multi-scale convolutional neural network based automated hippocampal subfield segmentation toolbox.

In this study, we developed a multi-scale Convolutional neural network based Automated hippocampal subfield Segmentation Toolbox (CAST) for automated segmentation of hippocampal subfields. Although training CAST required approximately three days on a single workstation with a high-quality GPU card, CAST can segment a new subject in less than 1 ​min even with GPU acceleration disabled, thus this method is more time efficient than current automated methods and manual segmentation. This toolbox is highly flexible with either a single modality or multiple modalities and can be easily set up to be trained with a researcher's unique data.

Early Detection of Mild Cognitive Impairment (MCI) in an At-Home Setting.

Emerging digital tools have the potential to enable a new generation of qualitative and quantitative assessment of cognitive performance. Moreover, the ubiquity of consumer electronics, such as smartphones and tablets, can be harnessed to support large-scale self-assessed cognitive screening with benefit to healthcare systems and consumers. A wide variety of apps, wearables, and new digital technologies are either available or in development for the detection of mild cognitive impairment (MCI), a risk factor for dementia.

Early Detection of Mild Cognitive Impairment (MCI) in Primary Care.

Mild cognitive impairment (MCI) is significantly misdiagnosed in the primary care setting due to multi-dimensional frictions and barriers associated with evaluating individuals' cognitive performance. To move toward large-scale cognitive screening, a global panel of clinicians and cognitive neuroscientists convened to elaborate on current challenges that hamper widespread cognitive performance assessment. This report summarizes a conceptual framework and provides guidance to clinical researchers and test developers and suppliers to inform ongoing refinement of cognitive evaluation.

Rationale for Early Diagnosis of Mild Cognitive Impairment (MCI) Supported by Emerging Digital Technologies.

Disease-modifying pharmacotherapies for Alzheimer's Disease (AD) are currently in late-stage clinical development; once approved, new healthcare infrastructures and services, including primary healthcare, will be necessary to accommodate a huge demand for early and large-scale detection of AD. The increasing global accessibility of digital consumer electronics has opened up new prospects for early diagnosis and management of mild cognitive impairment (MCI) with particular regard to AD. This new wave of innovation has spurred research in both academia and industry, aimed at developing and validating a new "digital generation" of tools for the assessment of the cognitive performance.

Effect of ApoE isoforms on mitochondria in Alzheimer disease.

Objective: To test the hypothesis that ApoE isoforms affect mitochondrial structure and function that are related to cognitive impairment in Alzheimer disease (AD), we systematically investigated the effects of ApoE isoforms on mitochondrial biogenesis and dynamics, oxidative stress, synapses, and cognitive performance in AD.

Methods: We obtained postmortem human brain tissues and measured proteins that are responsible for mitochondrial biogenesis (peroxisome proliferator-activated receptor-gamma coactivator-1α [PGC-1α] and sirtuin 3 [SIRT3]), for mitochondrial dynamics (mitofusin 1 [MFN1], mitofusin 2 [MFN2], and dynamin-like protein 1 [DLP1]), for oxidative stress (superoxide dismutase 2 [SOD2] and forkhead-box protein O3a [Foxo3a]), and for synapses (postsynaptic density protein 95 [PSD95] and synapsin1 [Syn1]). A total of 46 cases were enrolled, including ApoE-ɛ4 carriers (n = 21) and noncarriers (n = 25).

Non-Amyloid Approaches to Disease Modification for Alzheimer's Disease: An EU/US CTAD Task Force Report.

While amyloid-targeting therapies continue to predominate in the Alzheimer's disease (AD) drug development pipeline, there is increasing recognition that to effectively treat the disease it may be necessary to target other mechanisms and pathways as well. In December 2019, The EU/US CTAD Task Force discussed these alternative approaches to disease modification in AD, focusing on tau-targeting therapies, neurotrophin receptor modulation, anti-microbial strategies, and the innate immune response; as well as vascular approaches, aging, and non-pharmacological approaches such as lifestyle intervention strategies, photobiomodulation and neurostimulation. The Task Force proposed a general strategy to accelerate the development of alternative treatment approaches, which would include increased partnerships and collaborations, improved trial designs, and further exploration of combination therapy strategies.

Evidence of Validity for a Newly Developed Digital Cognitive Test Battery.

Clinical practice still relies heavily on traditional paper-and-pencil testing to assess a patient's cognitive functions. Digital technology has the potential to be an efficient and powerful alternative, but for many of the existing digital tests and test batteries the psychometric properties have not been properly established. We validated a newly developed digital test battery consisting of digitized versions of conventional neuropsychological tests.

Brain volumes and dual-task performance correlates among individuals with cognitive impairment: a retrospective analysis.

Cognitive impairment (CI) is a prevalent condition characterized by loss of brain volume and changes in cognition, motor function, and dual-tasking ability. To examine associations between brain volumes, dual-task performance, and gait and balance in those with CI to elucidate the mechanisms underlying loss of function. We performed a retrospective analysis of medical records of patients with CI and compared brain volumes, dual-task performance, and measures of gait and balance.