Medicine and Health Sciences Commons^™

Random Forest-Integrated Analysis In Ad And Late Brain Transcriptome-Wide Data To Identify Disease-Specific Gene Expression, Xinxing Wu, Chong Peng, Peter T. Nelson, Qiang Cheng

Sanders-Brown Center on Aging Faculty Publications

Alzheimer's disease (AD) is a complex neurodegenerative disorder that affects thinking, memory, and behavior. Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently identified common neurodegenerative disease that mimics the clinical symptoms of AD. The development of drugs to prevent or treat these neurodegenerative diseases has been slow, partly because the genes associated with these diseases are incompletely understood. A notable hindrance from data analysis perspective is that, usually, the clinical samples for patients and controls are highly imbalanced, thus rendering it challenging to apply most existing machine learning algorithms to directly analyze such datasets. Meeting this data analysis challenge is …

Editorial: Roles Of Sleep Disruption And Circadian Rhythm Alterations On Neurodegeneration And Alzheimer's Disease, Marilyn J. Duncan, Sigrid C. Veasey, Phyllis Zee

Neuroscience Faculty Publications

No abstract provided.

The Link Between Diabetes Mellitus And Tau Hyperphosphorylation: Implications For Risk Of Alzheimer's Disease, Amy L. Hobday, Mayur S. Parmar

HPD Articles

Diabetes mellitus (DM) is characterized by hyperglycemia caused by a lack of insulin, insulin resistance, or both. It is associated with the development of secondary complications resulting in several comorbidities. Recent studies have revealed an increased risk of developing cognitive dysfunction or dementia in diabetes patients. Diabetes mellitus is considered a risk factor for many neurodegenerative diseases, including Alzheimer's disease (AD). There is increasing evidence to support a link between DM and AD. Studies have shown the dysfunction of insulin signaling in the brain, resulting in increased tau protein phosphorylation (hyperphosphorylation), a hallmark and biomarker of AD pathology, leading to …

Analysis Of High-Risk Pedigrees Identifies 12 Candidate Variants For Alzheimer's Disease, Craig C. Teerlink, Justin B. Miller, Elizabeth L. Vance, Lyndsay A. Staley, Jeffrey Stevens, Justina P. Tavana, Matthew E. Cloward, Madeline L. Page, Louisa Dayton, Alzheimer's Disease Genetics Consortium, Lisa A. Cannon-Albright, John S. K. Kauwe

Institute for Biomedical Informatics Faculty Publications

INTRODUCTION: Analysis of sequence data in high-risk pedigrees is a powerful approach to detect rare predisposition variants.

METHODS: Rare, shared candidate predisposition variants were identified from exome sequencing 19 Alzheimer's disease (AD)-affected cousin pairs selected from high-risk pedigrees. Variants were further prioritized by risk association in various external datasets. Candidate variants emerging from these analyses were tested for co-segregation to additional affected relatives of the original sequenced pedigree members.

RESULTS: AD-affected high-risk cousin pairs contained 564 shared rare variants. Eleven variants spanning 10 genes were prioritized in external datasets: rs201665195 (ABCA7), and rs28933981 (TTR) were previously …

Relationship Between Global Cognition And Cardiovascular Risk Factors, Alexia Sebghati

Health, Human Performance and Recreation Undergraduate Honors Theses

Alzheimer’s disease (AD) is currently affecting the lives of 5.8 million Americans and is expected to double within the next 30 years. With an aging populace of baby boomers, this will place great economic strain on the U.S. creating a burden of almost $1 trillion in healthcare costs. Currently, there is no cure for AD. However, studies report that many individuals with AD experience changes in the brain up to 10-15 years before the disease’s onset. It is imperative to detect future risk of developing AD or mild cognitive impairment (MCI) before significant cognitive changes arise. Many of the risk …

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 …