Neurosciences Commons^™

Trc-Pad: Accelerating Recruitment Of Ad Clinical Trials Through Innovative Information Technology, G. A. Jimenez-Maggiora, S. Bruschi, R. Raman, O. Langford, M. Donohue, M. S. Rafii, R. A. Sperling, J. L. Cummings, P. S. Aisen, Trc-Pad Investigators

School of Medicine Faculty Research

Background The Trial-Ready Cohort for Preclinical/ Prodromal Alzheimer's Disease (TRC-PAD) Informatics Platform (TRC-PAD IP) was developed to facilitate the efficient selection, recruitment, and assessment of study participants in support of the TRC-PAD program. Objectives Describe the innovative architecture, workflows, and components of the TRC-PAD IP. Design The TRC-PAD IP was conceived as a secure, scalable, multi-tiered information management platform designed to facilitate high-throughput, cost-effective selection, recruitment, and assessment of TRC-PAD study participants and to develop a learning algorithm to select amyloid-bearing participants to participate in trials of early-stage Alzheimer's disease. Setting TRC-PAD participants were evaluated using both web-based and in-person …

The Trial-Ready Cohort For Preclinical And Prodromal Alzheimer’S Disease (Trc-Pad): Experience From The First 3 Years, S. Walter, O. G. Langford, T. B. Clanton, G. A. Jimenez-Maggiora, R. Raman, M. S. Rafii, E. J. Shaffer, R. A. Sperling, J. L. Cummings, P. S. Aisen, Trc-Pad Investigators

School of Medicine Faculty Research

Background The Trial-Ready Cohort for Preclinical and Prodromal Alzheimer's disease (TRC-PAD) aims to accelerate enrollment for Alzheimer's disease (AD) clinical trials by remotely identifying and tracking individuals who are at high risk for developing symptoms of AD, and referring these individuals to in-person cognitive and biomarker evaluation with the purpose of engaging them in clinical trials. A risk algorithm using statistical modeling to predict brain amyloidosis will be refined as TRC-PAD advances with a maturing data set. Objectives To provide a summary of the steps taken to build this Trial-Ready cohort (TRC) and share results of the first 3 years …

The Trial-Ready Cohort For Preclinical/Prodromal Alzheimer’S Disease (Trc-Pad) Project: An Overview, P. S. Aisen, R. A. Sperling, J. L. Cummings, M. C. Donohue, O. Langford, G. A. Jimenez-Maggiora, R. A. Rissman, M. S. Rafii, S. Walter, T. B. Clanton, R. Raman

School of Medicine Faculty Research

The Trial-Ready Cohort for Preclinical/prodromal Alzheimer’s Disease (TRC-PAD) project is a collaborative effort to establish an efficient mechanism for recruiting participants into very early stage Alzheimer’s disease trials. Clinically normal and mildly symptomatic individuals are followed longitudinally in a web-based component called the Alzheimer’s Prevention Trial Webstudy (APT Webstudy), with quarterly assessment of cognition and subjective concerns. The Webstudy data is used to predict the likelihood of brain amyloid elevation; individuals at relatively high risk are invited for in-person assessment in the TRC screeing phase, during which a cognitive battery is administered and Apolipoprotein E genotype is obtained followed by …

Recruitment Into The Alzheimer Prevention Trials (Apt) Webstudy For A Trial-Ready Cohort For Preclinical And Prodromal Alzheimer’S Disease (Trc-Pad), S. Walter, T. B. Clanton, O. G. Langford, M. S. Rafii, E. J. Shaffer, J. D. Grill, G. A. Jimenez-Maggiora, R. A. Sperling, J. L. Cummings, P. S. Aisen, Trc-Pad Investigators

School of Medicine Faculty Research

Background The Alzheimer Prevention Trials (APT) Webstudy is the first stage in establishing a Trial-ready Cohort for Preclinical and Prodromal Alzheimer's disease (TRC-PAD). This paper describes recruitment approaches for the APT Webstudy. Objectives To remotely enroll a cohort of individuals into a web-based longitudinal observational study. Participants are followed quarterly with brief cognitive and functional assessments, and referred to Sites for in-clinic testing and biomarker confirmation prior to enrolling in the Trial-ready Cohort (TRC). Design Participants are referred to the APT Webstudy from existing registries of individuals interested in brain health and Alzheimer's disease research, as well as through central …

The Influence Of Cerebellar Transcranial Direct Current Stimulation On Motor Function In Parkinson’S Disease, Lidio Lima De Albuquerque

UNLV Theses, Dissertations, Professional Papers, and Capstones

Parkinson's disease (PD) is the most common movement disorder and the second most common neurodegenerative disorder. PD is characterized by dopaminergic cell loss in the substantia nigra pars compacta, which leads to a reduction in dopamine in the striatum. These physiological mechanisms lead to a number of motor impairments such as bradykinesia, rigidity, tremor, and postural instability that severely limit the ability of individuals with PD to perform many essential daily living activities. Although current pharmacological, surgical, and physical exercise treatment approaches are valuable they are either only mildly effective, expensive, or associated with a variety of side effects. Therefore, …

Restructuring Of The Axon Initial Segment In Mouse Models Of Neurodevelopmental Disorders, Rachel Ali Rodriguez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Neurodevelopmental disorders (NDDs) affect more than 36% of children in countries with low- and middle- incomes (Boivin, 2015; McCoy, 2016). Interestingly, these heterogeneous disorders share a high incidence of epileptic seizures, suggesting a shared pathology. Seizures result when neuronal firing activity becomes disturbed and neurons fire excessively or in unregulated patterns. A key site in the control of neuronal firing patterns is the axon initial segment (AIS), where the local density of proteins and the morphology of the AIS in part determine the firing of neurons. We hypothesized that a disruption in the morphology and/or composition of the AIS can …

Advances In Management Of Neuropsychiatric Syndromes In Neurodegenerative Diseases, Jeffrey Cummings, Aaron Ritter, Kasia Rothenberg

School of Medicine Faculty Research

Purpose of Review Neuropsychiatric syndromes (NPS) are common in neurodegenerative disorders (NDD). This review describes the role of NPS in the diagnosis of NDD, criteria for the diagnosis of NPS, management of NPS, and agents in clinical trials for NPS. Recent Findings NPS play an increasingly important role in the diagnosis of NDD. Consensus diagnostic criteria have evolved for psychosis, depression, agitation, and apathy in NDD. With one exception—pimavanserin is approved for the treatment of hallucinations and delusions in Parkinson’s disease—there are no drugs approved by the FDA for treatment of NPS in NDD. Trials show that atypical antipsychotics reduce …

Further Analyses Of The Safety Of Verubecestat In The Phase 3 Epoch Trial Of Mild-To-Moderate Alzheimer’S Disease, Michael F. Egan, Yuki Mukai, Tiffini Voss, James Kost, Julie Stone, Christine Furtek, Erin Mahoney, Jeffrey L. Cummings, Pierre N. Tariot, Paul S. Aisen, Bruno Vellas, Christopher Lines, David Michaelson

Integrated Health Sciences Faculty Research

Background: Verubecestat, a BACE1 inhibitor that reduces Aβ levels in the cerebrospinal fluid of humans, was not effective in a phase 3 trial (EPOCH) of mild-to-moderate AD and was associated with adverse events. To assist in the development of BACE1 inhibitors, we report detailed safety findings from EPOCH. Methods: EPOCH was a randomized, double-blind, placebo-controlled 78-week trial evaluating verubecestat 12 mg and 40 mg in participants with mild-to-moderate AD diagnosed clinically. The trial was terminated due to futility close to its scheduled completion. Of 1957 participants who were randomized and took treatment, 652 were assigned to verubecestat 12 mg, 652 …

Reduced Gabaergic Signaling At The Axon Initial Segment Decreases Vigilance State Transitioning, Austin John Boren

UNLV Theses, Dissertations, Professional Papers, and Capstones

Sleep is a highly regulated homeostatic process that is disrupted in an estimated 50-70 million Americans. Regulation of sleep depends upon coordinated signaling of multiple neurotransmitter systems. In particular, inhibitory gamma-aminobutyric acid (GABA) signaling is required to suppress wake-active brain regions in order to initiate and maintain sleep states. GABA type A receptors (GABAARs) are ionotropic receptors with subunit compositions uniquely enriched on subcellular domains of target cells. α2 subunit-containing GABAARs are the primary target of GABA released onto the axon initial segment (AIS), a site critical for phasing the oscillatory activity of cortical cells. α2-containing GABAARs have previously been …

Changes In Hippocampal-Anterior Cingulate Cortex Interactions During Remote Memory Recall, Ryan A. Wirt

UNLV Theses, Dissertations, Professional Papers, and Capstones

Spatial memory is an important cognitive process that relies on extensive neural networks throughout the brain. The hippocampus (HC) is important for the formation of these memories but over time, in a process referred to as consolidation, recall becomes increasingly reliant on other brain areas. The anterior cingulate cortex (ACC), a region within the medial prefrontal cortex, is important for spatial learning, spatial working memory, and remote memory recall, but the mechanisms underlying recall processes are still unknown. To better understand the role of the ACC and HC during memory recall, we introduced rodents into a series of spatially and …

Treatment Combinations For Alzheimer’S Disease: Current And Future Pharmacotherapy Options, Jeffrey L. Cummings, Gary Tong, Clive Ballard

Integrated Health Sciences Faculty Research

Although Alzheimer’s disease (AD) is the world’s leading cause of dementia and the population of patients with AD continues to grow, no new therapies have been approved in more than a decade. Many clinical trials of single-agent therapies have failed to affect disease progression or symptoms compared with placebo. The complex pathophysiology of AD may necessitate combination treatments rather than monotherapy. The goal of this narrative literature review is to describe types of combination therapy, review the current clinical evidence for combination therapy regimens (both symptomatic and disease-modifying) in the treatment of AD, describe innovative clinical trial study designs that …

Modeling Reveals The Dependence Of Hippocampal Neurogenesis Radiosensitivity On Age And Strain Of Rats, Eliedonna Cacao, Sidath Kapukotuwa, Francis A. Cucinotta

Health Physics and Diagnostic Sciences Faculty Research

Cognitive dysfunction following radiation treatment for brain cancers in both children and adults have been correlated to impairment of neurogenesis in the hippocampal dentate gyrus. Various species and strains of rodent models have been used to study radiation-induced changes in neurogenesis and these investigations have utilized only a limited number of doses, dose-fractions, age and time after exposures conditions. In this paper, we have extended our previous mathematical model of radiation-induced hippocampal neurogenesis impairment of C57BL/6 mice to delineate the time, age, and dose dependent alterations in neurogenesis of a diverse strain of rats. To the best of our knowledge, …

An Evaluation Of Alzheimer's Disease-Related Pathology In Two Different Models Of Diabetes In Immune-Challenged Mice, Andrew Scott Murtishaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome are related disorders with wide-ranging and devastating effects that can be observed throughout the body. One important and understudied organ of damage is the brain. Clinical and epidemiological studies have found that T2DM, and more specifically hyperinsulinemia, significantly increases the risk of cognitive decline and increases the likelihood of Alzheimer’s disease (AD) and other forms of dementia in the elderly. Insulin has slightly different functions in the peripheral body than in the central nervous system and the dysregulation of these functions may contribute to the onset and progression of late-life neurodegenerative …

Common Ribs Of Inhibitory Synaptic Dysfunction In The Umbrella Of Neurodevelopmental Disorders, Rachel Ali Rodriguez, Christina Joya, Rochelle M. Hines

Psychology Faculty Research

The term neurodevelopmental disorder (NDD) is an umbrella term used to group together a heterogeneous class of disorders characterized by disruption in cognition, emotion, and behavior, early in the developmental timescale. These disorders are heterogeneous, yet they share common behavioral symptomatology as well as overlapping genetic contributors, including proteins involved in the formation, specialization, and function of synaptic connections. Advances may arise from bridging the current knowledge on synapse related factors indicated from both human studies in NDD populations, and in animal models. Mounting evidence has shown a link to inhibitory synapse formation, specialization, and function among Autism, Angelman, Rett …

Freedom With Responsibility: A Consensus Strategy For Preventing Injury, Death, And Disability From Firearm Violence, Ronald M. Stewart Md, Facs, Deborah A. Kuhls Md, Facs, Michael F. Rotondo Md, Facs, Eileen M. Bulger Md, Facs

School of Medicine Faculty Research

We are surgeons who have committed our personal and professional lives to reducing needless suffering from injury. As leaders in the American College of Surgeons Committee on Trauma (ACS COT), we have put our hearts and souls into reducing firearm violence, yet we continue to experience the senseless tragedy of mass shooting events and the daily impact of violence on our patients and our communities. Two of us (DK, RMS) personally cared for innocent victims in 2 of the largest mass shootings in modern American history: the Las Vegas, NV and Sutherland Springs, TX tragedies, which, within a little more …

Predicting Risk Factors Of Working Aged Hemorrhagic Stroke Patients In A Tertiary Teaching Hospital In Chiang Mai, Suphannee Triamvisit, Wilaiwan Chongruksut, Wanarak Watcharasaksilp, Rujee Rattanasathien

Asian/Pacific Island Nursing Journal

Stroke is the third leading cause of morbidity and mortality in Thailand accounting for a significant and increasing share of hospital costs. The purpose of this project is to study the epidemiology of the prevalence and its predicting factors of working aged hemorrhagic stroke (HS) patients admitted at a tertiary teaching hospital in Chiang Mai, Thailand.

We conducted a five-year retrospective descriptive study. The subjects in this study were patients diagnosed with HS, between 15-59 years of age, and admitted to a tertiary teaching hospital in Chiang Mai, Thailand from January 2009 to December 2013. A total of …

Proof-Of-Concept Testing Of A Real-Time Mhealth Measure To Estimate Postural Control During Walking: A Potential Application For Mild Traumatic Brain Injuries, Hyunhwa Lee, Sunchul Lee, Laura Salado, Jonica Estrada, Jacob White, Venkatesan Muthukumar, Szu-Ping Lee, Sambit Mohapatra

Nursing Faculty Research

Background: Most individuals with mild traumatic brain injury (mTBI) experience post-injury deficits in postural control. Currently available measures of postural control are lab-based or supervised, which may hinder timely symptom assessment for individuals with mTBI, including Asian populations, who do not seek initial screening post-injury. In this proof-of-concept testing study, we introduce a real-time mobile health (mHealth) system to measure postural control during walking. The proposed mHealth system can be used for home-based symptom assessment and management of mTBI. Methods: In our proposed mHealth system, a smartwatch, a smartphone, and a cloud server communicate to measure, collect, and store body …

Exercise, Learning And Emotional Health: Interdisciplinary Approaches To Translational Action, Tessa L. Koschel

UNLV Theses, Dissertations, Professional Papers, and Capstones

Exercise positively effects physical, psychological and neurological wellbeing. Though the population at large is becoming increasingly aware of the multi-faceted benefits of exercise, the majority of people fail to meet daily exercise recommendations. Largely, demands of everyday life such as work, school and family take priority over fitness. The issue therefore becomes a matter of time. In a world of media multi-tasking and immediate gratification, the challenge to health professionals becomes incorporation and manipulation of these consistencies to improve exercise uptake and adherence. Focus must shift from the idea of making additional time for exercise, to adding exercise to time …

An Evaluation Of Gabab Receptors On Modulating Neuroinflammation In A Non-Transgenic Animal Model Of Alzheimer's Disease, Monica Bolton

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and distinct neuropathological hallmarks, including amyloid beta plaques and neurofibrillary tau tangles (NFT). Although the etiology remains to be discovered, several risk factors exist that significantly contribute to developing AD. Diabetes is one of the major risk factors associated with AD and is characterized by disrupted insulin signaling that may contribute to or exacerbate AD pathologies. Furthermore, both disorders result in increased neuroinflammation. Considerable evidence has demonstrated that a chronic inflammatory response, in particular chronic microglia activation, promotes A production as well as the hyperphosphorylation of tau through …

The Psychophysiological Correlates Of Personality, Trauma, Posttraumatic Stress Disorder And Social Support, Meghan E. Pierce

UNLV Theses, Dissertations, Professional Papers, and Capstones

Theories considering the etiology of psychopathy suggest that trauma exposure, specifically childhood maltreatment and sexual abuse, is related to the development of callous-unemotional traits in children and adolescents, which are precursors to psychopathic traits in adulthood. Furthermore, posttraumatic stress disorder has an opposite relationship with many of the emotional and behavioral components of the two-factor model of psychopathy. Specifically, PTSD is positively associated to IA and traits associated with it and negatively associated with FD. Thus, this study sought to expand upon the current theories of a trauma-based etiology of psychopathy by investigating the relationship between trauma, PTSD, and psychopathic …

Neural Processes Underlying Auditory Context Effects, Breanne Yerkes

UNLV Theses, Dissertations, Professional Papers, and Capstones

Auditory information within our natural environments is disorganized and often ambiguous, leaving our auditory systems with a complex task: organizing sound into coherent objects. The auditory system uses both current and prior information to assist in completing this task. The influences of previous context on current perception have been referred to as context effects. A contrastive context effect results in a current perception that is opposite of what is expected based on the physical stimulus properties presented during an immediate context. A facilitative context effect results in a current perception that is the same as the perception during the immediate …

Assessing Clinical Significance Of The Immediate Post-Concussion Assessment And Cognitive Testing Battery When Comparing Adjusted And Unadjusted Rci Methods For Different Ranges Of Baseline Scores, Ashley N. Figaro

UNLV Theses, Dissertations, Professional Papers, and Capstones

The growing concern revolving around the dangers of sports-related concussions have led to the most recent implementation of neurocognitive (NC) test batteries as a means to objectively determine the presence of a cognitive defect. Whereas any other sports-related injury can be diagnosed with tools such as an x-ray or MRI, a concussion represents a metabolic disturbance that cannot be identified by these diagnostic tools. Many neurocognitive test batteries employ statistical techniques to derive cut off scores in order to represent significant or insignificant changes as compared to individual baseline scores, or pre-established normative values. If an individuals’ post-injury score exceeds …

The Effect Of Sleep On Perceptual Learning And Memory Consolidation, Vanessa Claire Irsik

UNLV Theses, Dissertations, Professional Papers, and Capstones

An ability to segregate speech accurately is essential given that most auditory environments contain other overlapping conversations or environmental noise. While perceiving speech among background noise can be difficult in and of itself, those with hearing impairments can experience considerable difficulty. While training has been shown to benefit perceptual segregation of trained sounds, it is unclear how such training transfers to sounds not included in a training regimen. The current study aimed to address this question by training listeners on a portion of sounds during a vowel segregation task, and subsequently testing on both the trained sounds and untrained sounds. …

Concordance Of The Montreal Cognitive Assessment With Standard Neuropsychological Measures, Sally J. Vogel, Sarah J. Banks, Jeffrey Cummings, Justin B. Miller

School of Medicine Faculty Research

Introduction: The concordance of the Montreal cognitive assessment (MoCA) with more comprehensive neuropsychological measures remains unclear. This study examined the individual MoCA domains with more comprehensive and commonly used neuropsychological measures to determine the degree of overlap. Methods: Data included individuals seen in an outpatient neurology clinic specializing in neurodegenerative disease who were administered the MoCA and also underwent neuropsychological assessment (n = 471). A principal component analysis with varimax rotation was completed using the MoCA domain scores and comprehensive neuropsychological evaluation measures. Results: Four factors emerged accounting for 55.6% of the variance: (1) visuospatial/executive functioning; (2) memory; (3) attention; …

Functional Capacity In Schizophrenia: Relationship Among Effort, Reinforcement Learning And Self-Beliefs, Sally J. Vogel

UNLV Theses, Dissertations, Professional Papers, and Capstones

Individuals with schizophrenia exhibit a wide range of complex neurocognitive, psychiatric and behavioral impairments. Recent research suggests that this complex array of symptoms can be at least partially accounted for by dysfunction in more basic mechanisms, such as the ability to learn from positive and negative reinforcement, or the ability to exert adequate effort when completing simple tasks. Evidence also suggests that deficits in these basic mechanisms may contribute to more complex symptoms, such as functional impairment. Also, the relationship between neurocognitive deficits and functional impairment has been found to be mediated by defeatist performance beliefs. However, studies have not …

A Comparison Of The Effects Of Different Doses Of Gabab Receptor Ligands On Spatial Learning And Memory And Memory Flexibility, Chelcie Heaney

UNLV Theses, Dissertations, Professional Papers, and Capstones

The principal inhibitory neurotransmitter in the brain, gamma amino-butyric acid (GABA), mediates several types of learning and memory. Of the two main receptor subtypes for GABA, the in vivo role of GABAB receptor in learning and memory is less well characterized and the current data often conflict. Based on the current literature, it is unclear, for instance, whether enhancing GABAergic activity via the GABAB receptor could be beneficial for or detrimental to learning and memory. Hippocampally-dependent learning and memory tasks are of particular interest due to their clinical relevance to patients with schizophrenia or Alzheimer’s disease, who exhibit impaired performance …

Postural Sway And Brain Hemispheric Power Spectral Density Under Different Attentional Focus Conditions, Sharon Jalene

UNLV Theses, Dissertations, Professional Papers, and Capstones

The purpose of this study was to determine the differences, if any, in the root mean square error (RMSE) of postural sway and hemispheric power spectral density (PSD) in the alpha and beta bands (8-12Hz and 12-25Hz) during different conditions of attentional focus (i.e., internal focus (IF), and external focus (EF) and a control condition (C)). Previous studies have shown that the adoption of IF and EF significantly alter motor performance and that EF promotes automaticity (Wulf, 2013). Sports performance and balance studies utilizing EEG spectral analyses report increased alpha oscillations during expert performance and stable balance and increased beta …

Hemispheric Asymmetry In The Perception Of Musical Pitch Structure, Matthew Adam Rosenthal

UNLV Theses, Dissertations, Professional Papers, and Capstones

Both the left and right hemispheres contribute to the perception of pitch structure

in music. Music researchers have attempted to explain the observed asymmetries in the perception of musical pitch structure by characterizing the dominant processing style of each hemisphere. However, no existing characterizations have been able to account for all of the empirical findings. To better explain existing empirical findings, this dissertation characterizes the left hemisphere as dominant in temporal pitch processing (i.e. with respect to the sequential ordering of pitches) and the right hemisphere as dominant in non-temporal pitch processing (i.e. without respect to the sequential ordering of …

The Effect Of Acute Lps-Induced Immune Activation And Brain Insulin Signaling Disruption In A Diabetic Model Of Alzheimer's Disease, Andrew Scott Murtishaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a neurodegenerative disorder marked by progressive cognitive impairments and pathological hallmarks that include amyloid plaques, neurofibrillary tangles, and neuronal loss. Several well-known mutations exist that lead to early-onset familial AD (fAD). However, these cases only account for a small percentage of total AD cases. The vast majority of AD cases are sporadic in origin (sAD) and are less clearly influenced by a single mutation but rather some combination of genetic and environmental risk.

The etiology of sAD remains unclear but numerous risk factors have been identified that increase the chance of developing AD. Among these risk …

Alternations Of Nmda And Gabab Receptor Function In Development: A Potential Animal Model Of Schizophrenia, Monica Bolton

UNLV Theses, Dissertations, Professional Papers, and Capstones

Schizophrenia is a debilitating mental disorder that affects up to 3% of the world population. The behavioral symptoms are categorized into positive and negative symptoms, which appear during late adolescence/early adulthood. Unfortunately, the underlying cellular and molecular mechanisms of the disease are poorly understood. Several hypotheses exist to explain mechanisms contributing to these behavioral alterations. One model proposes that a reduced function of the NMDA glutamate receptor on specific GABAergic interneurons may be responsible for deficits in schizophrenia. Post-mortem investigations provide evidence of reductions in both glutamate and GABA-related proteins in patients with schizophrenia. Further, GABAergic interneurons that are activated …