Medicine and Health Sciences Commons^™

The Impact Of Alzheimer Disease On Semantic Knowledge, Maileen G. Ulep

UNLV Theses, Dissertations, Professional Papers, and Capstones

The research furthers the understanding of the impact of Alzheimer disease (AD) on cognition and the organization of semantic knowledge in the brain, which might contribute to the development of diagnostic and staging tools, and interventions to palliate cognitive deficits. The disruption of semantic knowledge in AD is well documented in the literature. Much of the existing research focuses on the general impact AD has on semantic knowledge. This study explores the impact of AD on specific domains of knowledge, chiefly, living kinds and artifacts, critical to ordinary functioning. The content, organization and structure of the investigated domains of knowledge …

Development Of A Novel Cognitive-Motor Dual Task Assessment Battery In Neurodegenerative Disease, Jason Longhurst

UNLV Theses, Dissertations, Professional Papers, and Capstones

Automaticity --- the ability to perform a task with directing attentional resources to its completion --- is commonly reduced among individuals with neurodegenerative diseases. These automaticity deficits result in impaired functional and daily activities and are sensitive to subtle, subclinical impairments. However, current measurement of automaticity by dual task paradigms is methodologically limited. In order to gain insight into the current state of the literature regarding cognitive-motor interference in symptomatic and prodromal neurodegenerative disease, the author of this dissertation conducted a scoping review (Chapter 1). To address the methodological limitations of current measurement of automaticity, a new measurement tool was …

Intepirdine As Adjunctive Therapy To Donepezil For Mild-To-Moderate Alzheimer’S Disease: A Randomized, Placebo-Controlled, Phase 3 Clinical Trial (Mindset), Frederick M. Lang, Yi Mo, Marwan Sabbagh, Paul Solomon, Merce Boada, Roy W. Jones, Giovanni B. Frisoni, Timo Grimmer, Bruno Dubois, Mark Harnett, Sarah R. Friedhoff, Shari Coslett, Jeffrey L. Cummings

Brain Health Faculty Publications

Introduction: A previous phase 2b study supported the use of the 5-HT6 receptor antagonist intepirdine as adjunctive therapy to donepezil for Alzheimer's disease (AD) dementia. A phase 3 study, MINDSET, was performed to test this hypothesis. Methods: MINDSET was a global, double-blind, randomized, placebo-controlled trial in 1315 mild-to-moderate AD dementia patients on stable donepezil. Patients received 35 mg/day intepirdine or placebo for 24 weeks. The co-primary endpoints were change from baseline to week 24 on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL). Results: There were no statistically significant differences between intepirdine …

Alzheimer's Disease Drug Development Pipeline: 2019, Jeffrey Cummings, Garam Lee, Aaron Ritter, Marwan Sabbagh, Kate Zhong

School of Medicine Faculty Publications

Introduction Alzheimer's disease (AD) has few available treatments, and there is a high rate of failure in AD drug development programs. Study of the AD drug development pipeline can provide insight into the evolution of drug development and how best to optimize development practices. Methods We reviewed clinicaltrials.gov and identified all pharmacologic AD trials of all agents currently being developed for treatment of AD. Results There are 132 agents in clinical trials for the treatment of AD. Twenty-eight agents are in 42 phase 3 trials; 74 agents are in 83 phase 2 trials; and 30 agents are in 31 phase …

The Price Of Progress: Funding And Financing Alzheimer's Disease Drug Development, Jeffrey Cummings, Carl Reiber, Parvesh Kumar

School of Medicine Faculty Publications

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. The National Institute on Aging, National Institute of Mental Health, National Institute of General Medical Sciences, and National Center for Advancing Translational Science all fund aspects of research in AD drug development. Non-National …

Biomedical Informatics Applications For Precision Management Of Neurodegenerative Diseases, Justin B. Miller, Guogen Shan, Joseph Lombardo, Gustavo Jimenez-Maggoria

Public Health Faculty Publications

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. Especially for neurodegenerative diseases, where an effective therapeutic agent has yet to be discovered, there remains a critical need for an interdisciplinary …

Inflammation As A Central Mechanism In Alzheimer's Disease, Jefferson W. Kinney, Shane M. Bemiller, Andrew S. Murtishaw, Amanda M. Leisgang, Arnold M. Salazar, Bruce T. Lamb

Psychology Faculty Research

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by cognitive decline and the presence of two core pathologies, amyloid β plaques and neurofibrillary tangles. Over the last decade, the presence of a sustained immune response in the brain has emerged as a third core pathology in AD. The sustained activation of the brain's resident macrophages (microglia) and other immune cells has been demonstrated to exacerbate both amyloid and tau pathology and may serve as a link in the pathogenesis of the disorder. In the following review, we provide an overview of inflammation in AD and a detailed …

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 …

The Effects Of Chronic Calcium Dysregulation On Behavioral And Pathological Features Of Alzheimer's Disease, Jonathan Sabbagh

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose etiology is unknown. Recent studies have implicated alterations in calcium homeostasis as a pathogenic contributor to AD. Calcium dysregulation has been observed in aged and AD brains, an event which could potentially facilitate the development of multiple pathologies observed in AD. Specifically, disrupting intracellular calcium levels in vitro has been demonstrated to increase amyloid-beta (Aβ) production, tau phosphorylation, and neuronal loss. However, there is a paucity of data on the behavioral and biochemical consequences of chronic in vivo perturbation of calcium homeostasis. In a series of experiments designed to evaluate the …