Mitochondrial Oxidative And Nitrosative Stress And Alzheimer Disease, D. Allan Butterfield, Debra Boyd-Kimball

Chemistry Faculty Publications

Oxidative and nitrosative stress are widely recognized as critical factors in the pathogenesis and progression of Alzheimer disease (AD) and its earlier stage, amnestic mild cognitive impairment (MCI). A major source of free radicals that lead to oxidative and nitrosative damage is mitochondria. This review paper discusses oxidative and nitrosative stress and markers thereof in the brain, along with redox proteomics, which are techniques that have been pioneered in the Butterfield laboratory. Selected biological alterations in—and oxidative and nitrosative modifications of—mitochondria in AD and MCI and systems of relevance thereof also are presented. The review article concludes with a section …

Integrating Affect Perception Tasks From The New York Emotion Battery Into A Comprehensive Measure Of Neuropsychological Change Across The Lifespan, Melinda A. Cornwell

Dissertations, Theses, and Capstone Projects

Background: The ability to perceive others’ emotions is a vital skill for social competency, impacting the success of personal and professional relationships (Brinton & Fujiki, 2011; Cassidy et al., 1992; Côté & Miners, 2006). According to Socioemotional Selectivity Theory (SST; Carstensen, 1991), human motivation develops to become more discerning in choosing milieus that yield the most gratifying return on the investment of personal resources (e.g., time, attention, and effort), perhaps explaining why some research findings indicate that older adults may demonstrate an affect perception (AP) bias described as a positivity effect (Reed et al., 2014). Moreover, AP predicts cognitive and …

Life Expectancy And Active Life Expectancy By Disability Status In Older U.S. Adults, Haomiao Jia, Erica I. Lubetkin

Publications and Research

Objectives

The Medicare Health Outcome Survey (HOS) is the largest longitudinal survey of the U.S. community-dwelling elderly population. This study estimated total life expectancy, active life expectancy (ALE), and disability-free life expectancy (DFLE) by disability status among HOS participants.

Methods

Data were from the Medicare HOS Cohort 15 (baseline 2012, follow-up 2014). We included respondents aged ≥ 65 years (n = 164,597). Participants’ disability status was assessed based on the following six activities of daily living (ADL): bathing, dressing, eating, getting in or out of chairs, walking, and using the toilet. The multi-state models were used to estimate life expectancy, …

Hypusination Of Eif5a Regulates Cytoplasmic Tdp-43 Aggregation And Accumulation In A Stress-Induced Cellular Model, Shayna Smeltzer, Zainuddin Quadri, Abraian Miller, Frank Zamudio, Jordan Hunter, Nicholas J.F. Stewart, Sheba Saji, Daniel C. Lee, Dale Chaput, Maj-Linda B. Selenica

Sanders-Brown Center on Aging Faculty Publications

TAR DNA-binding protein 43 (TDP-43) is a nuclear RNA/DNA binding protein involved in mRNA metabolism. Aberrant mislocalization to the cytoplasm and formation of phosphorylated/aggregated TDP-43 inclusions remains the hallmark pathology in a spectrum of neurodegenerative diseases, including frontotemporal disorders and Alzheimer's disease. Eukaryotic Translation Initiation Factor 5A undergoes a unique post-translation modification of lysine to hypusine (K50), which determines eIF5A binding partners. We used a sodium arsenite-induced cellular stress model to investigate the role of hypusinated eIF5A (eIF5A^HypK50) in governing TDP-43 cytoplasmic mislocalization and accumulation in stress granule. Our proteomics and functional data provide evidence that eIF5A interacts …

Cardiorespiratory Fitness Diminishes The Effects Of Age On White Matter Hyperintensity Volume, Nathan F. Johnson, Ahmed A. Bahrani, David K. Powell, Gregory A. Jicha, Brian T. Gold

Physical Therapy Faculty Publications

White matter hyperintensities (WMHs) are among the most commonly observed marker of cerebrovascular disease. Age is a key risk factor for WMH development. Cardiorespiratory fitness (CRF) is associated with increased vessel compliance, but it remains unknown if high CRF affects WMH volume. This study explored the effects of CRF on WMH volume in community-dwelling older adults. We further tested the possibility of an interaction between CRF and age on WMH volume. Participants were 76 adults between the ages of 59 and 77 (mean age = 65.36 years, SD = 3.92) who underwent a maximal graded exercise test and structural brain …

Feasibility Of Dual-Task Gait To Estimate Alzheimer's Related Cognitive Decline In Down Syndrome, Kathryn L. Van Pelt, Lisa Mason Koehl, Allison M. Caban-Holt, Amelia J. Anderson-Mooney, Elizabeth Head, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

Introduction: The striatum and frontal lobes have been shown to have early Alzheimer's disease (AD) neuropathology and are critical for motor and cognitive function. We hypothesized gait would be associated with early-stage dementia in Down syndrome (DS), a cohort at risk for AD.

Methods: Twenty-eight participants with DS were enrolled in the study. Participants walked at their self-selected pace and while completing a dual task (counting, obstacle, or counting+obstacle).

Results: All participants were able to complete the self-paced condition and 78.57-96.42% completed the dual-task conditions. There was a trend for greater dual-task effects on gait velocity based on dementia diagnosis. …

Limbic-Predominant Age-Related Tdp-43 Encephalopathy Differs From Frontotemporal Lobar Degeneration, John L. Robinson, Sílvia Porta, Filip G. Garrett, Panpan Zhang, Sharon X. Xie, Eunran Suh, Vivianna M. Van Deerlin, Erin L. Abner, Gregory A. Jicha, Justin M. Barber, Virginia M-Y Lee, Edward B. Lee, John Q. Trojanowski, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

TAR-DNA binding protein-43 (TDP-43) proteinopathy is seen in multiple brain diseases. A standardized terminology was recommended recently for common age-related TDP-43 proteinopathy: limbic-predominant, age-related TDP-43 encephalopathy (LATE) and the underlying neuropathological changes, LATE-NC. LATE-NC may be co-morbid with Alzheimer’s disease neuropathological changes (ADNC). However, there currently are ill-defined diagnostic classification issues among LATE-NC, ADNC, and frontotemporal lobar degeneration with TDP-43 (FTLD-TDP). A practical challenge is that different autopsy cohorts are composed of disparate groups of research volunteers: hospital- and clinic-based cohorts are enriched for FTLD-TDP cases, whereas community-based cohorts have more LATE-NC cases. Neuropathological methods also differ across laboratories. Here, …

Understanding The Impact Of Social Distancing On Older Adults And Senior Organizations To Better Adapt Towards A New Normal, Salina Jivan

San Marcos, Summer 2020

COVID-19 brought about social distancing mandates that posed as a new barrier to meaningful social participation in the community. The purpose of this project was to understand the impact of social distancing on older adults and senior organizations to better inform the role of OT in helping seniors adapt towards a new normal within the community. A qualitative study and needs assessment were performed through phone interviews with seniors and organizations that support them from around the United States. Themes highlighted seniors desire for social contact and cautious return to the community once mandates are lifted. Both seniors and organizations …

Impact And Mortality Of Covid-19 On People Living With Dementia: Cross-Country Report, Aida Suárez-González, Gill Livingston, Lee Fay Low, Suzanne Cahill, Niamh Hennelly, Walter D. Dawson, Wendy Weidner, Martina Bocchetta, Cleusa P. Ferri, Jordi A. Matias-Guiu, Multiple Additional Authors

Institute on Aging Publications

This report brings together international evidence on the impact of the COVID-19 pandemic on people living with dementia and an overview of international policy and practice measures to mitigate the impact of COVID-19 among people living with dementia.

Key Findings

• We have collected data on impact and mortality of COVID-19 in people living with dementia in 9 countries: The United Kingdom (UK), Spain, Ireland, Italy, Australia, the United States (US), India, Kenya and Brazil.
• The share of people whose deaths were linked to COVID-19 in care homes who had dementia ranges from 29% to 75% across those countries. Within countries, …

Therapeutic Trem2 Activation Ameliorates Amyloid-Beta Deposition And Improves Cognition In The 5xfad Model Of Amyloid Deposition, Brittani R. Price, Tiffany L. Sudduth, Erica M. Weekman, Sherika Johnson, Danielle Hawthorne, Abigail E. Woolums, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Triggering receptor expressed on myeloid cell-2 (TREM2) is a lipid and lipoprotein binding receptor expressed by cells of myeloid origin. Homozygous TREM2 mutations cause early onset progressive presenile dementia while heterozygous, point mutations triple the risk of Alzheimer's disease (AD). Although human genetic findings support the notion that loss of TREM2 function exacerbates neurodegeneration, it is not clear whether activation of TREM2 in a disease state would result in therapeutic benefits. To determine the viability of TREM2 activation as a therapeutic strategy, we sought to characterize an agonistic Trem2 antibody (AL002a) and test its efficacy and mechanism of action …

Involuntary Treatment In Dementia Care At Home: Results From The Netherlands And Belgium, Angela M. H. J. Mengelers, Vincent R. A. Moermans, Michel H. C. Bleijlevens, Hilde Verbeek, Elizabeth Capezuti, Frans Tan, Koen Milisen, Jan P. H. Hamers

Publications and Research

Aims and objectives: To gain insight into the request, use and associated factors of involuntary treatment in people with dementia (PwD) receiving professional home care in the Netherlands and Belgium.

Background: Most of the PwD remain living at home as long as possible. Due to complex care needs, this can result in an increased risk for care provided against the wishes of the client and/or to which the client resists, referred to as involuntary treatment.

Design: Secondary data analyses of two cross-sectional surveys.

Methods: Dementia case managers and district nurses filled in a questionnaire for each PwD in their …

Gwep Goals Of Care, Audrey Dunstan, Nyann Biery Ms

Research Scholars Poster Presentation

No abstract provided.

Sexually Transmitted Infections And The 65 And Older Population: Knowledge And Perceived Risk, Alexus Miranda

UNLV Theses, Dissertations, Professional Papers, and Capstones

Sexually transmitted infections (STI) can impact all persons. Since 2000, the number of STIs has steadily increased among persons aged 50 years and older in the United States (Purpora, 2012). Persons over the age of 60 accounted for the biggest increase of in-office treatments of STIs between 2014 and 2017 (Howley, 2018). The purpose of this study was to use the Sexual Health Model to examine the relationship between various predictors and these persons’ perceived risk of STIs, their STI knowledge, and other barriers that impact the sexual health of persons 65 years of age and older. This study used …

Life Expectancy And Active Life Expectancy By Marital Status Among Older U.S. Adults Results From The U.S. Medicare Health Outcome Survey (Hos), Haomiao Jia, Erica I. Lubetkin

Publications and Research

Background: Previous investigations of the relationship between marital status and life expectancy and healthy life expectancy rely on the assumption that participants will remain in a given marital status until death. This study estimated total life expectancy (TLE) and active life expectancy (ALE) for respondents by their baseline marital status using a large longitudinal sample of the U.S. community-dwelling elderly population.

Methods: Data were from the Medicare Health Outcomes Survey Cohort 15 (2012 baseline, 2014 follow-up). We included respondents aged ≥65 years (n = 164,597). Multi-state models estimated TLE and ALE by marital status to allow participants' marital status to …

Investigating A Multimodal Approach To Clinical Diagnosis Of Mild Cognitive Impairment And Alzheimer’S Disease, Sean M. Flannery

Psychology Theses & Dissertations

An estimated 5.8 million Americans suffer from dementia due to Alzheimer’s disease (AD), with that number projected to grow to 13.8 million by mid-century (Alzheimer’s Association, 2019). Mild cognitive impairment (MCI) describes the stage between normal cognitive decline that comes with aging and a dementia diagnosis (Peterson, 1999). Due to a lack of a cure or particularly effective treatment, a major goal of treatment is to focus on improving quality of life (Budson & Solomon, 2016). An early and accurate diagnosis can address this goal in a variety of ways. Despite the high prevalence and immense amount of research in …

Machine Learning Approaches For Fracture Risk Assessment: A Comparative Analysis Of Genomic And Phenotypic Data In 5130 Older Men, Qing Wu, Fatma Nasoz, Jongyun Jung, Bibek Bhattarai, Mira V. Han

School of Public Health Faculty Research

The study aims were to develop fracture prediction models by using machine learning approaches and genomic data, as well as to identify the best modeling approach for fracture prediction. The genomic data of Osteoporotic Fractures in Men, cohort Study (n = 5130), were analyzed. After a comprehensive genotype imputation, genetic risk score (GRS) was calculated from 1103 associated Single Nucleotide Polymorphisms for each participant. Data were normalized and split into a training set (80%) and a validation set (20%) for analysis. Random forest, gradient boosting, neural network, and logistic regression were used to develop prediction models for major osteoporotic fractures …

Geriatrics In Clinical Practice And Beyond: Brain Health, The Sixth Vital Sign?, Nannette Hoffman

HCA Healthcare Journal of Medicine

Brain health in middle age and geriatric patients will take on greater importance for health care practitioners in our aging society. This article discusses various approaches clinicians can use for their patients to promote and improve brain health. These are generally the same lifestyle adoptions for cerebrovascular disease and cardiovascular disease prevention: weight management, exercise, and blood pressure and cholesterol lowering. Social stimulation and cognitive activities may also be important for the elderly.

Aging, Vulnerability And Managing Type 2 Diabetes During A Pandemic, Jasmin Tahmaseb-Mcconatha, Jacqueline Magnarelli, Lauren Stricker

Psychology Faculty Publications

Older men and women have been found to be more vulnerable to negative outcomes should they contract Covid19, particularly if they also have comorbid conditions such as type 2 diabetes. Cultural, racial, ethnic, and social class differences exist in vulnerability to Covid19 and in the prevalence of type 2 diabetes. In the United States, for example, diabetes rates for minority and immigrant populations are higher than for non-Hispanic whites. During the a social health crisis, it is helpful to explore the ways that illness management and associated vulnerability influences the ways that minority elders attempt to maintain and promote their …

Investigating The Impact Of The Nursing Practice Environment (Npe) On Central Line-Associated Bloodstream Infections (Clabsi) Among Older Adults In The Intensive Care Unit (Icu), Kristen A. Cribbs

Dissertations and Theses

Background: Health care–associated infections, resulting from treatment received for medical or surgical conditions in a health care setting, represent a critical public health and patient safety issue, exacting substantial medical, social, and economic costs. The costliest among the leading causes of preventable health care-associated infections is central-line associated bloodstream infections (CLABSI), to which older adults (age 65 years and older) are particularly susceptible, especially during intensive care unit (ICU) stays. A rich body of research has empirically linked the quality of the nursing practice environment (NPE) in hospitals to both positive and negative patient outcomes; yet, surprisingly few studies have …

Older Adults’ Perspectives On Occupational Supports In Alternative Housing Communities, A'Via Coleman, Lisa Goolsby, Kara Lurvey, Elizabeth Von Achen, Heather Veverica

Older Adult

The Problem: Many older adults in the United States wish to age in place but may find their current living environment is not suitable as they age. Alternative housing supports may improve the ability of older adults to live in their own home and community safely while performing necessary occupations.

The Resolution: Alternative housing communities offer a variety of supports that older adults value having access to, even if they are not always utilized including transportation, social interaction, volunteer opportunities, home maintenance, an accessible location, and the togetherness of community.

Increasing Polst Documentation For Patient Transfers From Long Term Care Facilities, Jennifer White, Md, Mari Siegel, Chris Haines, Chris Pitsch, Heather Peiritsch, Erica Westlake

Health Equity and Quality Improvement (HEQI) Summit

With an increase in patients from long term care facilities being admitted to the hospital, a lack of goals of care documentation became evident and presented the providers with many unknowns regarding patient care.

Without documentation and sick with COVID, patients cannot always advocate for themselves. This problem is worsened by the ban on visitors, preventing surrogate decision makers from being in the room.

There is a need for providers at long term care facilities to have these goals of care discussions, for COVID specific circumstances and for long term care.

Experience With A Comprehensive Multidisciplinary Geriatric Oncology Center, Michael Weissberger, Md, Ms, Emma De Louw, Md, Kristine Swartz, Md, Lauren Hersh, Md, Andrew Chapman, Do, Facp

Health Equity and Quality Improvement (HEQI) Summit

Research Goals

1. 1. Describe the population seen in the SAOC over the past 6 years
2. Remediate and complete the EPIC flowsheets
3. Merge data with existing RedCAP data

Frailty And Post-Operative Outcomes In Adult Hip Fracture Patients, Melissa Yager

Dissertations

Abstract

Background/ Purpose: The majority of adult hip fracture patients never return to their pre-fracture functional level and have a poor quality of life (Kistler, Nicholas, Kates, & Friedman, 2015; Pioli et al., 2016; Sheehan et al., 2018). The prevalence of frailty in adult hip fracture patients is estimated at 51%. Frail patients with hip fractures are twice as likely to have a complication (Kistler et al., 2015). Extant studies have examined frailty and hip fractures independently, nonetheless, a gap in the literature exists with few investigations of the connection between frailty and post-operative outcomes after hip fracture. The purpose …

Ccl2 Overexpression In The Brain Promotes Glial Activation And Accelerates Tau Pathology In A Mouse Model Of Tauopathy, Aurelie Joly-Amado, Jordan Hunter, Zainuddin Quadri, Frank Zamudio, Patricia V. Rocha-Rangel, Deanna Chan, Anisha Kesarwani, Kevin Nash, Daniel C. Lee, Dave Morgan, Marcia N. Gordon, Maj-Linda B. Selenica

Sanders-Brown Center on Aging Faculty Publications

Innate immune activation is a major contributor to Alzheimer’s Disease (AD) pathophysiology, although the mechanisms involved are poorly understood. Chemokine C-C motif ligand (CCL) 2 is produced by neurons and glial cells and is upregulated in the AD brain. Transgene expression of CCL2 in mouse models of amyloidosis produces microglia-induced amyloid β oligomerization, a strong indication of the role of these activation pathways in the amyloidogenic processes of AD. We have previously shown that CCL2 polarizes microglia in wild type mice. However, how CCL2 signaling contributes to tau pathogenesis remains unknown. To address this question, CCL2 was delivered via recombinant …

Brain Structure Changes Over Time In Normal And Mildly Impaired Aged Persons, Charles D. Smith, Linda J. Van Eldik, Gregory A. Jicha, Frederick A. Schmitt, Peter T. Nelson, Erin L. Abner, Richard J. Kryscio, Richard R. Murphy, Anders H. Andersen

Neurology Faculty Publications

Structural brain changes in aging are known to occur even in the absence of dementia, but the magnitudes and regions involved vary between studies. To further characterize these changes, we analyzed paired MRI images acquired with identical protocols and scanner over a median 5.8-year interval. The normal study group comprised 78 elders (25M 53F, baseline age range 70-78 years) who underwent an annual standardized expert assessment of cognition and health and who maintained normal cognition for the duration of the study. We found a longitudinal grey matter (GM) loss rate of 2.56 ± 0.07 ml/year (0.20 ± 0.04%/year) and a …

Correlations Of Calf Muscle Macrophage Content With Muscle Properties And Walking Performance In Peripheral Artery Disease, Kate Kosmac, Marta Gonzalez-Freire, Mary M. Mcdermott, Sarah H. White, R. Grace Walton, Robert L. Sufit, Lu Tian, Lingyu Li, Melina R. Kibbe, Michael H Criqui, Jack M. Guralnik, Tamar S. Polonsky, Christiaan Leeuwenburgh, Luigi Ferrucci, Charlotte A. Peterson

Physical Therapy Faculty Publications

Background

Peripheral artery disease (PAD) is a manifestation of atherosclerosis characterized by reduced blood flow to the lower extremities and mobility loss. Preliminary evidence suggests PAD damages skeletal muscle, resulting in muscle impairments that contribute to functional decline. We sought to determine whether PAD is associated with an altered macrophage profile in gastrocnemius muscles and whether muscle macrophage populations are associated with impaired muscle phenotype and walking performance in patients with PAD.

Methods and Results

Macrophages, satellite cells, and extracellular matrix in gastrocnemius muscles from 25 patients with PAD and 7 patients without PAD were quantified using immunohistochemistry. Among patients …

Implementation Of Post Falls Huddles In Skilled Nursing Facility, Princess Lomax

Evidence-Based Practice Project Reports

The purpose of this paper is to discuss the quality improvement project, implementation of the post fall huddle in a long-term care facility. Falls are the most common problem in adults 65 years and older. Falls in this population can have devastating effects, often leading to significant changes in morbidity or death. Adults in long term care settings have an increased risk of falling and having a subsequent fall due to an acute illness, weakness, or confusion (CDC, 2015). At the skilled facility, there has been a significant increase in hospitalizations due to injuries sustained from falls. To address this …

Integrating Geriatric Assessment And Genetic Profiling To Personalize Therapy Selection In Older Adults With Acute Myeloid, Vijaya R. Bhatt

Theses & Dissertations

Integrating geriatric assessment for patient profiling and genetic profiling of leukemic cells represents an innovative approach to personalize therapy selection in older adults with acute myeloid leukemia (AML). We report results of a pre-planned interim analysis of a pragmatic phase II trial that utilized this strategy to personalize therapy. Patients ≥60 years with a new diagnosis of AML underwent geriatric assessment prior to initiation of treatment. Geriatric assessment of physical function, cognitive function and comorbidity burden were used to determine fitness for chemotherapy. Patients with good or intermediate-risk AML received intensive chemotherapy such as anthracycline and cytarabine (7+3) if determined …

A Qualitative Analysis Of The Barriers Faced By Nursing Assistants And Medication Aides In The Care Of Dysphagia Residents, Lauren Kreuzberg

Honors Program: Senior Projects (Public)

Dysphagia refers to the symptom of difficulty in swallowing that accompanies several prevalent conditions in the older adult population, including amyotrophic lateral sclerosis (ALS, Lou Gehrig’s Disease), stroke, Parkinson’s Disease, Multiple Sclerosis, dementia, various cancers, and brain tumors (Allari, 2014). Many older adults who suffer from these conditions reside in nursing facilities, where most of their care is provided by certified nursing assistants (CNAs) and medication aides (MAs). However, the extent of these workers’ knowledge and competence in providing care to nursing home residents with dysphagia is vastly under-researched. The qualitative analysis investigates themes among interviews with fifteen CNAs and …

The Coronavirus And The Risks To The Elderly In Long-Term Care, William Gardner, David States, Nicholas Bagley

Articles

The elderly in long-term care (LTC) and their caregiving staff are at elevated risk from COVID-19. Outbreaks in LTC facilities can threaten the health care system. COVID-19 suppression should focus on testing and infection control at LTC facilities. Policies should also be developed to ensure that LTC facilities remain adequately staffed and that infection control protocols are closely followed. Family will not be able to visit LTC facilities, increasing isolation and vulnerability to abuse and neglect. To protect residents and staff, supervision of LTC facilities should remain a priority during the pandemic.