Medicine and Health Sciences Commons^™

Exploring The Lived Experiences Of Daughters/ Daughters-In-Law Providing Primary Informal Care To Their Mothers/ Mothers-In-Law With Dementia, Sarah Macfarlane

Theses and Dissertations (Comprehensive)

Abstract

Objective

As the senior population in Canada rises, more middle aged residents of Canada will find themselves taking on a caregiving role, often times for a parent with dementia. This research examines the lived experiences of daughters/daughters-in-law providing primary informal care to their mothers/mothers-in-law with dementia in order to understand the motivations, effects, and transitions within caregiving relationships.

Methods

Phenomenology was the theoretical orientation used to guide this research and captured individuals’ lived experiences. Background questionnaires were administered initially, followed by one-on-one semi-structured interviews which were transcribed verbatim upon completion for data analysis. Field notes, member checks, and triangulation …

Selective Suppression Of The Α Isoform Of P38 Mapk Rescues Late-Stage Tau Pathology, Nicole Maphis, Shanya Jiang, Guixiang Xu, Olga N. Kokiko-Cochran, Saktimayee M. Roy, Linda J. Van Eldik, D. Martin Watterson, Bruce T. Lamb, Kiran Bhaskar

Sanders-Brown Center on Aging Faculty Publications

Background: Hyperphosphorylation and aggregation of tau protein are the pathological hallmarks of Alzheimer’s disease and related tauopathies. We previously demonstrated that the microglial activation induces tau hyperphosphorylation and cognitive impairment via activation of p38 mitogen-activated protein kinase (p38 MAPK) in the hTau mouse model of tauopathy that was deficient for microglial fractalkine receptor CX3CR1.

Method: We report an isoform-selective, brain-permeable, and orally bioavailable small molecule inhibitor of p38α MAPK (MW181) and its effects on tau phosphorylation in vitro and in hTau mice.

Results: First, pretreatment of mouse primary cortical neurons with MW181 completely blocked inflammation-induced p38α MAPK activation and AT8 …

Behavioural Inflexibility And White Matter Inflammation In An Aged Happ Rat With Subcortical Stroke, Aaron M. Regis

Electronic Thesis and Dissertation Repository

The interactions between Alzheimer’s disease (AD) and ischemic stroke pathology are of key interest in the development of post-stroke cognitive decline. While clinical and experimental studies have suggested an interaction, the mechanisms whereby these conditions interact to worsen cognition haven’t been fully revealed. This study aimed to combine rodent models of AD and stroke in an aged rat and assess the behavioural and histological outcomes. An injection of endothelin-1 (ET-1), a potent vasoconstrictor into the basal ganglia of a rat with human amyloid precursor protein (hAPP) overexpression (F344Tg) was followed up 3 months later to assess behavioural flexibility, memory and …

Vectored Intracerebral Immunization With The Anti-Tau Monoclonal Antibody Phf1 Markedly Reduces Tau Pathology In Mutant Tau Transgenic Mice, Wencheng Liu, Lingzhi Zhao, Brittany Blackman, Mayur Parmar, Man Ying Wong, Thomas Woo, Fangmin Yu, Maria J. Chiuchiolo, Dolan Sondhi, Stephen M. Kaminsky, Ronald G. Crystal, Steven M. Paul

HPD Articles

UNLABELLED: Passive immunization with anti-tau monoclonal antibodies has been shown by several laboratories to reduce age-dependent tau pathology and neurodegeneration in mutant tau transgenic mice. These studies have used repeated high weekly doses of various tau antibodies administered systemically for several months and have reported reduced tau pathology of ∼40-50% in various brain regions. Here we show that direct intrahippocampal administration of the adeno-associated virus (AAV)-vectored anti-phospho-tau antibody PHF1 to P301S tau transgenic mice results in high and durable antibody expression, primarily in neurons. Hippocampal antibody levels achieved after AAV delivery were ∼50-fold more than those reported following repeated systemic …

Methods For Diagnosing And Treating Alzheimer's Disease (Ad) Using The Molecules That Stabilize Intracellular Calcium (Ca2+) Release, Philip W. Landfield, John C. Gant, Eric M. Blalock, Kuey-Chu Chen, Olivier Thibault, Nada M. Porter

Pharmacology and Nutritional Sciences Faculty Patents

The subject technology relates, in part, to a method of treating Alzheimer's Disease (AD), early-stage AD, elevated risk of AD, mild cognitive impairment (MCI), or other forms of age-related cognitive decline in a subject in need thereof by administering to the subject a molecule that promotes calcium-release stabilization in ryanodine receptors (RyRs) and/or inosital triphosphate receptors (InsP3Rs) in brain cells. Diagnostic methods using calcium-release stabilizing immunophilins, junctophilins or calmodulin are also disclosed.

Life With Alzheimer's Disease, Sarah Houtz

Student Brochures

No abstract provided.

Extracellular Vesicle-Associated Aβ Mediates Trans-Neuronal Bioenergetic And Ca2+-Handling Deficits In Alzheimer's Disease Models, Erez Eitan, Emmette R. Hutchison, Krisztina Marosi, James Comotto, Maja Mustapic, Saket M. Nigam, Caitlin Suire, Chinmoyee Maharana, Gregory A. Jicha, Dong Liu, Vasiliki Machairaki, Kenneth W. Witwer, Dimitrios Kapogiannis, Mark P. Mattson

Sanders-Brown Center on Aging Faculty Publications

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder in which aggregation-prone neurotoxic amyloid β-peptide (Aβ) accumulates in the brain. Extracellular vesicles (EVs), including exosomes, are small 50–150 nm membrane vesicles that have recently been implicated in the prion-like spread of self-aggregating proteins. Here we report that EVs isolated from AD patient cerebrospinal fluid and plasma, from the plasma of two AD mouse models, and from the medium of neural cells expressing familial AD presenilin 1 mutations, destabilize neuronal Ca²⁺ homeostasis, impair mitochondrial function, and sensitize neurons to excitotoxicity. EVs contain a relatively low amount of Aβ but have an …

Diabetes Is Associated With Cerebrovascular But Not Alzheimer's Disease Neuropathology, Erin L. Abner, Peter T. Nelson, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Randall L. Woltjer, Nigel J. Cairns, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Kamal Masaki, Suzanne L. Tyas, David A. Bennett, Julie A. Schneider, Zoe Arvanitakis

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: The relationship of diabetes to specific neuropathologic causes of dementia is incompletely understood.

METHODS: We used logistic regression to evaluate the association between diabetes and infarcts, Braak neurofibrillary tangle stage, and neuritic plaque score in 2365 autopsied persons. In a subset of >1300 persons with available cognitive data, we examined the association between diabetes and cognition using Poisson regression.

RESULTS: Diabetes increased odds of brain infarcts (odds ratio [OR] = 1.57, P < .0001), specifically lacunes (OR = 1.71, P < .0001), but not Alzheimer's disease neuropathology. Diabetes plus infarcts was associated with lower cognitive scores at end of life than infarcts or diabetes alone, and diabetes plus high level of Alzheimer's neuropathologic changes was associated with lower mini-mental state examination scores than the pathology alone.

DISCUSSION: This study supports the conclusions that diabetes increases the risk of cerebrovascular but not Alzheimer's disease pathology, and at least some of diabetes' relationship to …

Evaluating The Therapeutic Effect Of An Hsp90 Inhibitor In Mouse Models Of Alzheimer’S Disease, Bin Wang

Theses and Dissertations (ETD)

The excessive accumulation of amyloid peptides (Aβ) represents one major pathological hallmark of Alzheimer’s disease (AD), which is most notably characterized by synaptic dysfunction. Strategies targeting heat shock protein 90 (Hsp90) inhibition have been widely investigated in the treatment of cancer for over two decades. Its application in the treatment of neurodegenerative diseases however, has emerged more recently in the last decade. The role of the Hsp90 chaperone in clearing misfolded protein aggregates has been well established (in vitro only), but its function in synaptic activity remains elusive.

In our study, we utilized a widely used Hsp90 inhibitor, 17-AAG …

Early-Onset Alzheimer’S: Should You Worry?, Troy Rohn

Biology Faculty Publications and Presentations

You have forgotten where you put your car keys, or you can’t seem to remember the name of your colleague you saw in the grocery store the other day. You fear the worst, that maybe these are signs of Alzheimer’s disease.

Plasma Neuronal Exosomal Levels Of Alzheimer's Disease Biomarkers In Normal Aging, Erin L. Abner, Gregory A. Jicha, Leslie M. Shaw, John Q. Trojanowski, Edward J. Goetzl

Sanders-Brown Center on Aging Faculty Publications

Plasma neuronal exosomal levels of pathogenic Alzheimer's disease (AD) proteins, cellular survival factors, and lysosomal proteins distinguish AD patients from control subjects, but changes in these exosomal proteins associated with normal aging have not been described for cognitively intact subjects. Plasma neuronal exosomal levels of P-T181-tau, P-S396-tau, Aβ_1-42, cathepsin D, repressor element 1-silencing transcription factor, and neurogranin were quantified longitudinally in cognitively intact older adults using two samples collected at 3- to 11-year intervals. Except for P-S396-tau, exosomal protein levels changed significantly with aging, but were largely outside the range observed in AD patients.

Reciprocity: Caring For America's Caregivers, Courtney Dunn

The Downtown Review

Should families be forced to choose between the health of a caregiver and patient? Through the eyes of a woman caring for her husband with Alzheimer's disease, we see that family caregivers suffer tremendous amounts of stress while caring for the patient. Despite the time and efforts required to care for someone with Alzheimer's disease, people every day choose this as an alternative to out-of-home care. This often leads to depression, anxiety, and physical stress which can result in series medical issues. Considering the increase of people with Alzheimer's disease in the United States, this article argues that support programs …

Motor And Hippocampal Dependent Spatial Learning And Reference Memory Assessment In A Transgenic Rat Model Of Alzheimer's Disease With Stroke, Jennifer L. Au, Nina Weishaupt, Hayley J. Nell, Shawn N. Whitehead, David F. Cechetto

Anatomy and Cell Biology Publications

Alzheimer's disease (AD) is a debilitating neurodegenerative disease that results in neurodegeneration and memory loss. While age is a major risk factor for AD, stroke has also been implicated as a risk factor and an exacerbating factor. The co-morbidity of stroke and AD results in worsened stroke-related motor control and AD-related cognitive deficits when compared to each condition alone. To model the combined condition of stroke and AD, a novel transgenic rat model of AD, with a mutated form of amyloid precursor protein (a key protein involved in the development of AD) incorporated into its DNA, is given a small …

AΒ40 Reduces P-Glycoprotein At The Blood-Brain Barrier Through The Ubiquitin-Proteasome Pathway, Anika M. S. Hartz, Yu Zhong, Andrea Wolf, Harry Levine Iii, David S. Miller, Björn Bauer

Sanders-Brown Center on Aging Faculty Publications

Failure to clear amyloid-β (Aβ) from the brain is in part responsible for Aβ brain accumulation in Alzheimer's disease (AD). A critical protein for clearing Aβ across the blood–brain barrier is the efflux transporter P-glycoprotein (P-gp) in the luminal plasma membrane of the brain capillary endothelium. P-gp is reduced at the blood–brain barrier in AD, which has been shown to be associated with Aβ brain accumulation. However, the mechanism responsible for P-gp reduction in AD is not well understood. Here we focused on identifying critical mechanistic steps involved in reducing P-gp in AD. We …

Alzheimer's Disease: Knowledge Of Early Detection, Risk Factors, And Treatment, Anna H. Smith, Katlyn S. Spadino

All Electronic Theses and Dissertations

Alzheimer's disease causes a progressive and irreversible decline in cognitive functioning. There are many people living with this disease, and the prevalence is expected to triple between 2010 and 2050. Many members of society are affected through either a personal diagnosis or the diagnosis of a family member. There have been numerous studies outlining risk factors, signs and symptoms, and treatments for this disease, but it is unknown if this has translated to greater public awareness. This study aims to assess the general adult population's knowledge of Alzheimer's disease. The participants are 35 to 70 years old and live in …

The Semantic Memory Imaging In Late Life Pilot Study, Michael Adam Sugarman

Wayne State University Dissertations

Introduction: Several functional magnetic resonance imaging (fMRI) studies have analyzed the famous name discrimination task (FNDT), an uncontrolled semantic memory probe requiring discrimination between famous and unfamiliar individuals. Completion of this simple task recruits a semantic memory network that has shown utility in determining risk for Alzheimer's disease (AD). Specific semantic memory probes using biographical information associated with famous individuals may build on previous findings and yield superior information regarding risk for AD.

Method: Sixteen cognitively intact elders completed the FNDT and two novel tasks during fMRI: Categories (matching famous individuals to occupational categories) and Attributes (matching famous individuals to …

Histological Evidence Of The Effect Of Oil Palm Phenolics In Atherogenic Diet Induced Rat Model Of Alzheimer’S Disease, Kenechukwu Monplaisir Monplaisir

Wayne State University Theses

BACKGROUND: Alzheimer’s disease (AD) is a neurodegenerative disease with the clinical presentation of memory loss and cognitive impairment. Alzheimer's disease pathology is the accumulation of beta amyloid plaques and neurofibrillary tangles.

METHOD: In this study atherogenic diet was used to induce AD in aged Brown Norway rats. The rats were assigned to the following four groups fed isocaloric diets; control group (C ),high cholesterol diet (H), high cholesterol + oil palm phenolics group (HP), high cholesterol + curcumin group (HC). The impact of oil palm phenolics (OPP) on neuronal health and its effect on amyloid deposition was evaluated using histology …

Oxidative Stress Induces Transient O‐Glcnac Elevation And Tau Dephosphorylation In Sh‐Sy5y Cells, Emese Katai, Jozsef Pal, Viktor Soma Poor, Rupeena Purewal, Attila Miseta, Tamas Nagy

Faculty & Staff Scholarship

O‐linked β‐N‐acetlyglucosamine or O‐GlcNAc modification is a dynamic post‐translational modification occurring on the Ser/Thr residues of many intracellular proteins. The chronic imbalance between phosphorylation and O‐GlcNAc on tau protein is considered as one of the main hallmarks of Alzheimer's disease. In recent years, many studies also showed that O‐GlcNAc levels can elevate upon acute stress and suggested that this might facilitate cell survival. However, many consider chronic stress, including oxidative damage as a major risk factor in the development of the disease. In this study, using the neuronal cell line SH‐SY5Y we investigated the dynamic nature of O‐GlcNAc …

Risk Of Alzheimer's Disease Among Older Hispanic/Latinos With Diabetes, Kathy Bianco

Walden Dissertations and Doctoral Studies

Alzheimer's disease (AD) is the 6th leading cause of death in older Americans. Currently there is no cure for AD, and even though the specific cause is unknown, diabetes mellitus type 2 (DM2) is regarded as a risk factor. Hispanics have a higher incidence of DM2 and possibly AD. I chose a life course theoretical model for this quantitative cross-sectional study to illuminate the variables most pertinent to a pathway from good health to poor health. The variables chosen were hypertension (HTN), obesity, smoking, stroke, dyslipidemia, and lower educational attainment. The research questions were used to examine biologic, metabolic, sociologic, …

Finding Chemopreventatives To Reduce Amyloid Beta In Yeast, Ian Macreadie, Costa Arvanitis, Prashant Bharadwaj

Research outputs 2014 to 2021

Alzheimer's disease (AD) is the most common form of age-related dementia with the latest report (WorldAlzheimerReport, 2015) showing 46.8 million people are currently affected by dementia. That number is expected to double every 20 years unless there is effective therapeutic intervention.

Editorial: Biology Of Cognitive Aging: Model Systems, Technologies, And Beyond, Shin Murakami

Faculty Publications & Research of the TUC College of Osteopathic Medicine

The author provides an introduction to a research issue of Frontiers in Genetics on models and techniques related to age-related memory impairment.

Comparing Biological Markers Of Alzheimer's Disease Across Blood Fraction And Platforms: Comparing Apples To Oranges, Sid E. O'Bryant, Simone Lista, Robert A. Rissman, Melissa Edwards, Fan Zhang, James Hall, Herik Zetterberg, Simon Lovestone, Veer Bular Gupta, Neill Graff-Radford, Ralph N. Martins, Andreas Jeromin, Stephen Waring, Esther Oh, Mitchel Kling, Laura D. Baker, Harald Hampel

Research outputs 2014 to 2021

Introduction:

This study investigated the comparability of potential Alzheimer's disease (AD) biomarkers across blood fractions and assay platforms.

Methods:

Nonfasting serum and plasma samples from 300 participants (150 AD patients and 150 controls) were analyzed. Proteomic markers were obtained via electrochemiluminescence or Luminex technology. Comparisons were conducted via Pearson correlations. The relative importance of proteins within an AD diagnostic profile was examined using random forest importance plots.

Results:

On the Meso Scale Discovery multiplex platform, 10 of the 21 markers shared > 50% of the variance across blood fractions (serum amyloid A R2 = 0.99, interleukin (IL)10 R2 = 0.95, fatty …

The Effects Of Latrepirdine On Amyloid-Β Aggregation And Toxicity, Tenielle Porter, Prashant Bharadwaj, David Groth, Adrian Paxman, Simon Laws, Ralph Martins, Guiseppe Verdile

Research outputs 2014 to 2021

Latrepirdine (DimebonTM) has been demonstrated to be a neuroprotective and cognition improving agent in neurodegenerative diseases that feature protein aggregation and deposition, such as Alzheimer's disease (AD). The accumulation of amyloid-β (Aβ) protein aggregates is a key event in the neurodegenerative process in AD. This study explores if latrepirdine modulation of protein aggregation contributes to its neuroprotective mechanism of action. Assessment of neuronal cell death showed that there was a significant reduction in lactate dehydrogenase release at an equimolar ratio of Aβ:latrepirdine and with lower concentrations of latrepirdine. The ability of latrepirdine to alter the formation of Aβ42 aggregates was …

An Examination Of Traumatic Brain Injury As A Risk Factor For Psychiatric Symptoms In Alzheimer’S Disease Patients, Jennifer F. Walch

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Introduction:

Dementia is a major public health issue both in the United States and worldwide. Alzheimer’s disease (AD) is widely considered to be the most prevalent type of dementia. While the hallmark AD symptom is profound memory loss, patients also commonly experience changes in personality and behavior. These changes often include depression, anxiety, social withdrawal, mood swings, irritability and aggression, changes in sleeping habits, and delusions.

Background:

Several studies have established a mechanistic link between traumatic brain injury (TBI) and the development of AD. However, it is unknown whether TBI contributes to the personality/behavior changes observed in many AD patients. …

Curcumin/Melatonin Hybrids As Neuroprotective Agents For Alzheimer's Disease, John Saathoff

Theses and Dissertations

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia, affecting ~5.2 million Americans. Current FDA approved medications provide mainly symptomatic relief and there are no agents available to delay or cure this disease. Multiple factors such as amyloid-β aggregates, dyshomeostasis of biometals, oxidative stress, and neuroinflammation have been implicated in the development of AD. Even though significant advances have been made in understanding the mechanisms leading to AD, the exact etiology still remains elusive. Given AD’s multifactorial nature, a multifunctional strategy of small molecule design would help to identify novel chemical templates. Recently our lab …