Big data and biomedical informatics: Preparing for the modernization of clinical neuropsychology.

Objective: Neuropsychology is poised for a fundamental shift as we modernize the ways in which behavior is measured. The amount and complexity of data generated by these new methods will be several orders of magnitude greater than what is currently created by analog measures and will quickly adopt characteristics of "Big Data." Adequate preparation for managing the influx of data will be critical for technology integration and modernization to be successful.

Current state of Alzheimer's fluid biomarkers.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with a complex and heterogeneous pathophysiology. The number of people living with AD is predicted to increase; however, there are no disease-modifying therapies currently available and none have been successful in late-stage clinical trials. Fluid biomarkers measured in cerebrospinal fluid (CSF) or blood hold promise for enabling more effective drug development and establishing a more personalized medicine approach for AD diagnosis and treatment.

Concussion reporting and perceived knowledge of professional fighters.

: For concussions to be effectively managed in sports, they need to be correctly identified and reported. The extent to which professional athletes correctly recognize concussions, and their willingness to report symptoms, is not yet well understood. Given the risk of head injuries leading to concussions across combat sports, insight into professional fighters' knowledge and reporting of concussive symptoms is essential to improve concussion management.

Insights into globalization: comparison of patient characteristics and disease progression among geographic regions in a multinational Alzheimer's disease clinical program.

Background: Globalization of clinical trials has important consequences for trial planning and interpretation. This study investigated heterogeneity in patient characteristics and outcomes among world regions in the global idalopirdine Phase 3 clinical program.

Methods: Data were pooled from three 24-week randomized controlled trials in patients aged ≥ 50 years with mild-to-moderate Alzheimer's disease (AD) (n = 2506).

Ten-year trends of palliative care utilization associated with multiple sclerosis patients in the United States from 2005 to 2014.

Multiple sclerosis (MS) is a chronic neuro-inflammatory disease of the central nervous system, associated with accumulation of irreversible neurological disabilities through both inflammatory relapses and progressive neurodegeneration. Patients with debilitating MS could benefit from palliative care perspectives both during relapses that lead to transient disability as well as later in the disease course when significant physical and cognitive disability have accrued. However, no data about palliative care utilization trends of MS patients are available.

Default Mode Network Lateralization and Memory in Healthy Aging and Alzheimer's Disease.

Lateralization of default mode network (DMN) functioning has been shown to change with age. Similarly, lateralization of frontal lobe function has been shown to decline in age. The impact of amyloid pathology and the progression of Alzheimer's disease (AD) on resting state lateralization has not been investigated.

Development, Application, and Results from a Precision-medicine Platform that Personalizes Multi-modal Treatment Plans for Mild Alzheimer's Disease and At-risk Individuals.

Introduction: Alzheimer's Disease (AD) is a progressive neurodegenerative condition in which individuals exhibit memory loss, dementia, and impaired metabolism. Nearly all previous single-treatment studies to treat AD have failed, likely because it is a complex disease with multiple underlying drivers contributing to risk, onset, and progression. Here, we explored the efficacy of a multi-therapy approach based on the disease risk factor status specific to individuals with AD diagnosis or concern.

Pimavanserin: Potential Treatment For Dementia-Related Psychosis.

Psychosis is common across dementia types with a prevalence of 20% to 70%. Currently, no pharmacologic treatment is approved for dementia-related psychosis. Atypical antipsychotics are frequently used to treat these disorders, despite significant safety concerns.

Network-based assessment of collaborative research in neuroscience.

Introduction: The purpose of this study was to describe collaborative research in neuroscience within the context of the Center for Neurodegeneration and Translational Neuroscience (CNTN), a Center of Biomedical Research Excellence supported by the National Institute of General Medical Science. Drawing upon research on the science of team science, this study investigated the way that interactions around research emerged over the course of establishing a new research center. The objectives were to document changes in research activity and describe how human research support infrastructure functioned to support the production of science.

Does taking statins affect the pathological burden in autopsy-confirmed Alzheimer's dementia?

Background: The efficacy of cholesterol lowering agents, specifically statins, in slowing the rate of decline of cognitive function in Alzheimer's disease (AD) patients is not yet fully understood. Our team's previously published paper showed that patients who used statins demonstrated no increase in cognitive decline in mild cognitive impairment when compared with nonusers. Further, AD patients on statins demonstrated a slight decreasing trend in cognitive decline.

Genetic Risk of Alzheimer's Disease: Three Wishes Now That the Genie is Out of the Bottle.

The availability and increasing popularity of direct-to-consumer genetic testing for the presence of an APOE4 allelle led the Alzheimer's Foundation of America Medical, Scientific and Memory Screening Advisory Board to identify three critical areas for attention: 1) ensure consumer understanding of test results; 2) address and limit potential negative consequences of acquiring this information; and 3) support linking results with positive health behaviors, including potential clinical trial participation. Improving access to appropriate sources of genetic counseling as part of the testing process is critical and requires action from clinicians and the genetic testing industry. Standardizing information and resources across the industry should start now, with the input of consumers and experts in genetic risk and health information disclosure.

Adaptive crossover designs for assessment of symptomatic treatments targeting behaviour in neurodegenerative disease: a phase 2 clinical trial of intranasal oxytocin for frontotemporal dementia (FOXY).

Background: There are currently no treatments for empathy deficits in neuropsychiatric disorders. Acute administration of the hormone oxytocin has been associated with symptomatic improvements across animal models and several neuropsychiatric disorders, but results of the majority of oxytocin randomised controlled trials (RCTs) of longer duration have been negative or inconclusive. This lack of efficacy of may be due to rapid habituation to oxytocin with chronic dosing.

Salivary beta amyloid protein levels are detectable and differentiate patients with Alzheimer's disease dementia from normal controls: preliminary findings.

Background: Peripheral diagnostics for Alzheimer's disease (AD) continue to be developed. Diagnostics capable of detecting AD before the onset of symptoms are particularly desirable, and, given the fact that early detection is imperative for alleviating long-term symptoms of the disease, methods which enable detection in the earliest stages are urgently needed. Saliva testing is non-invasive, and saliva is easy to acquire.

Current understanding of magnetic resonance imaging biomarkers and memory in Alzheimer's disease.

Alzheimer's disease (AD) is caused by a cascade of changes to brain integrity. Neuroimaging biomarkers are important in diagnosis and monitoring the effects of interventions. As memory impairments are among the first symptoms of AD, the relationship between imaging findings and memory deficits is important in biomarker research.

Neuroimaging and neuropsychological assessment of freezing of gait in Parkinson's disease.

Introduction: Freezing of gait (FOG) is a disabling phenomenon characterized by a brief, episodic absence or reduction of forward progression of the feet despite the intention to walk. It is a common cause of falls and mortality in cases with Parkinson's disease (PD). This article reviews neuropsychological and neuroimaging studies to date and introduces a new study of multimodal imaging and cognition in PD-FOG.

Advances in functional magnetic resonance imaging data analysis methods using Empirical Mode Decomposition to investigate temporal changes in early Parkinson's disease.

Introduction: Previous neuroimaging studies of Parkinson's disease (PD) patients have shown changes in whole-brain functional connectivity networks. Whether connectivity changes can be detected in the early stages (first 3 years) of PD by resting-state functional magnetic resonance imaging (fMRI) remains elusive. Research infrastructure including MRI and analytic capabilities is required to investigate this issue.

Statistical advances in clinical trials and clinical research.

Introduction: New treatments for neurodegenerative disease are urgently needed, and clinical trial methods are an essential component of new drug development. Although a parallel-group study design for neurological disorder clinical trials is commonly used to test the effectiveness of a new treatment as compared to placebo, it does not efficiently use information from the on-going study to increase the success rate of a trial or to stop a trial earlier when the new treatment is indeed ineffective.

Methods: We review some recent advances in designs for clinical trials, including futility designs and adaptive designs.

Biomedical informatics applications for precision management of neurodegenerative diseases.

Modern medicine is in the midst of a revolution driven by "big data," rapidly advancing computing power, and broader integration of technology into healthcare. Highly detailed and individualized profiles of both health and disease states are now possible, including biomarkers, genomic profiles, cognitive and behavioral phenotypes, high-frequency assessments, and medical imaging. Although these data are incredibly complex, they can potentially be used to understand multi-determinant causal relationships, elucidate modifiable factors, and ultimately customize treatments based on individual parameters.

Neuroscience learning from longitudinal cohort studies of Alzheimer's disease: Lessons for disease-modifying drug programs and an introduction to the Center for Neurodegeneration and Translational Neuroscience.

The development of disease-modifying therapies for Alzheimer's disease is an urgent public health emergency. Recent failures have highlighted the significant challenges faced by drug-development programs. Longitudinal cohort studies are ideal for promoting understanding of this multifactorial, slowly progressive disease.

The price of progress: Funding and financing Alzheimer's disease drug development.

Introduction: Advancing research and treatment for Alzheimer's disease (AD) and the search for effective treatments depend on a complex financial ecosystem involving federal, state, industry, advocacy, venture capital, and philanthropy funding approaches.

Methods: We conducted an expert review of the literature pertaining to funding and financing of translational research and drug development for AD.

Results: The federal government is the largest public funder of research in AD.

Dopamine transporter availability reflects gastrointestinal dysautonomia in early Parkinson disease.

Background: Constipation is a prodromal feature of Parkinson's disease (PD) and the gastrointestinal (GI) tract is implicated in the pathogenesis of PD. However, no studies have demonstrated ante-mortem relationships between nigrostriatal dysfunction and GI dysautonomia in PD.

Methods: The Scale for Outcomes in Parkinson's disease for Autonomic Symptoms (SCOPA-AUT) assesses dysautonomia in the multi-center Parkinson's Progression Marker Initiative (PPMI).

Nicotinic Acetylcholine Receptor Agonists for the Treatment of Alzheimer's Dementia: An Update.

Unlabelled: A significant portion of the clinical phenotype observed in Alzheimer's disease (AD) occurs through nicotinic acetylcholine receptors (nAChRs). Degeneration of cholinergic neurons, combined with aberrant nAChR expression and activation partially through amyloid-beta peptide (Aβ)-nAChR leads to upregulation of pro-inflammatory pathways and subsequently the progressive cognitive decline of AD. Interestingly, the cholinergic anti-inflammatory pathway is also mediated through nAChR particularly α7 nAChR.

What predicts falls in Parkinson disease?: Observations from the Parkinson's Foundation registry.

Background: We undertook this study to identify patients with Parkinson disease (PD) with no or rare falls who may progress to frequent falling by their next annual follow-up visit.

Methods: We analyzed data in the National Parkinson Foundation Quality Improvement Initiative database to identify factors predicting which patients with PD with no or rare falls at the baseline visit will report at least monthly falls at the annual follow-up visit. Multivariable models were constructed using logistic regression.

Changes in regional cerebral blood flow associated with a 45 day course of the ketogenic agent, caprylidene, in patients with mild to moderate Alzheimer's disease: Results of a randomized, double-blinded, pilot study.

Background: Caprylidene is a ketogen that, when metabolized, produces the ketones beta-hydroxybutyrate and acetoacetate, which can cross the blood brain barrier. It has been hypothesized that ketone bodies can be used as an alternate energy source by neurons with impaired glucose utilization. Caprylidene has been shown to improve cognition in patients with mild-to-moderate Alzheimer's disease (AD) who lacked an AD-predisposing allele (ɛ4) of the gene for apolipoprotein E.