Medicine and Health Sciences Commons^™

An Ewas Of Dementia Biomarkers And Their Associations With Age, African Ancestry, And Ptsd, Mark W. Miller, Erika J. Wolf, Xiang Zhao, Mark W. Logue, Sage E. Hawn

Psychology Faculty Publications

Background

Large-scale cohort and epidemiological studies suggest that PTSD confers risk for dementia in later life but the biological mechanisms underlying this association remain unknown. This study examined this question by assessing the influences of PTSD, APOE ε4 genotypes, DNA methylation, and other variables on the age- and dementia-associated biomarkers Aβ40, Aβ42, GFAP, NfL, and pTau-181 measured in plasma. Our primary hypothesis was that PTSD would be associated with elevated levels of these markers.

Methods

Analyses were based on data from a PTSD-enriched cohort of 849 individuals. We began by performing factor analyses of the biomarkers, the results of which …

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 …

Adult Day Services In Maine: Benefits, Challenges, And Opportunities, Elizabeth Gattine Jd, Eileen Griffin Jd, Kimberly I. Snow Mhsa, Ba

Disability & Aging

In Maine and nationally, adult day services tend to be underfunded and underutilized compared to other types of long term services and supports (LTSS). In part, investment in adult day services is hampered by a lack of standardized data collection and limited research on issues of accessibility, cost-effectiveness, and the impact of adult day services on the broader health system. Lack of uniformity in state regulatory frameworks for licensing, program design, service delivery, and other administrative requirements further complicates cross-state comparisons. Considering these limitations, a key goal of this report is to provide a more detailed and comprehensive understanding of …

The Effects Of Physical Function And Genetics On Cognition And Blood Biomarkers In Individuals At-Risk For Alzheimer’S Disease And Related Dementias, Joshua Louis Gills

Graduate Theses and Dissertations

Alzheimer’s disease and related dementia (ADRD) rates are expected to triple by the year 2050. Early detection and specific mitigation efforts are warranted to blunt the alarming rate. Physical function (PF) declines with age, but higher physical function is associated with better cognitive functioning in middle-to- older age individuals. Moreover, greater physical activity (PA) is associated with better global cognition; however, Apoliporotein e4 carriers may not gain the same benefits with exercise. Additionally, plasma phosphorylated tau 217 (p-tau217) has been identified as a novel diagnostic ADRD biomarker which needs further research to examine associations with risk factors. Therefore, the aims …

Examining The Mental Health Of Older Hispanic/Latino Adults: Relationship Between Psycho-Social-Cultural Factors And Depressive Symptomatology, Anna Prado

Theses and Dissertations

The most prevalent disorders affecting the older adult population worldwide are dementia and depression. Ethnic minorities are disproportionately more likely to be affected by these two distressing and debilitating conditions. Hispanic/Latino older adults encounter numerous psycho-social-cultural factors that influence health behaviors, attitudes, and beliefs in positive and negative ways. Presently, research on the influence of these factors on Hispanic/Latino mental health is highly inconsistent. The purpose of the present study is to examine the relationship between selected psycho-social-cultural factors and the mental health of older Hispanic/Latino adults. Using data from the Health and Retirement Study, the association between the Hispanic/Latino …

Comparison Of Longitudinal Changes In Resting State Functional Magnetic Resonance Imaging Between Alzheimer’S And Healthy Controls, Berk Can Yilmaz

Theses

Resting State Functional Magnetic Resonance Imaging (rs-fMRI) is a technique that is widely used for analyzing brain function using different approaches and methods. This study involves rs-fMRI analysis of Blood Oxygenation Level Dependent (BOLD) signals acquired from Alzheimer’s disease (AD) Patients and Healthy Controls (HC). Each subject in the study had both functional and anatomical images with at least one rs-fMRI scan with their Anatomical (T1) scans. Previous rs-fMRI studies have demonstrated that AD shows differences in Amplitude of Low Frequency (<0.1 Hz) Fluctuations (ALFF), and Regional Homogeneity (ReHo) measures according to HCs.

The aim of the study is to investigate individual and group level differences using ReHo and mALFF related …

Basal Forebrain Volume Reliably Predicts The Cortical Spread Of Alzheimer's Degeneration, Sara Fernández-Cabello, Martin Kronbichler, Koene R.A. Van Dijk, James A. Goodman, R. Nathan Spreng, Taylor W. Schmitz

Brain and Mind Institute Researchers' Publications

© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. Alzheimer's disease neurodegeneration is thought to spread across anatomically and functionally connected brain regions. However, the precise sequence of spread remains ambiguous. The prevailing model used to guide in vivo human neuroimaging and non-human animal research assumes that Alzheimer's degeneration starts in the entorhinal cortices, before spreading to the temporoparietal cortex. Challenging this model, we previously provided evidence that in vivo markers of neurodegeneration within the nucleus basalis of Meynert (NbM), a subregion of the basal forebrain heavily populated by cortically projecting cholinergic neurons, …

Will "Social Distancing" Lead To Future "Research Distancing": A Reflection On Covid-19 Impacts On Alzheimer's Disease Research, Shoshana H. Bardach, Allison K. Gibson, Elizabeth K. Rhodus, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

Coronavirus disease 19 (COVID-19) has dramatically altered everyday life, including the field of Alzheimer's disease (AD) research. This perspective article explores some of the ways in which COVID-19 has already impacted the field, anticipates some of the long-lasting effects, and explores strategies for addressing current and future needs. Areas of impact include study integrity, regulatory and industry issues, and participant engagement. Proposed strategies for addressing these challenges include analytic methods to deal with large degrees of missing data and development of patient-centered, user-friendly, remote data collection tools and assessments. We also highlight the importance of maintaining participant well-being as a …

Memory-Based Viewing: A Potential Marker Of Pathological Aging, Jenna Blujus

Theses and Dissertations

Markers of cognitive impairment are needed to distinguish normal from pathological aging prior to the onset of clinical symptomology to improve Alzheimer’s disease (AD) treatment or prevention efforts. AD pathology is believed to develop years or even decades prior to diagnosis in medial temporal lobe subregions that provide input to the hippocampus (Braak & Braak, 1991), disrupting the ability of the hippocampus to bind individual elements of an experience to form cohesive memory representations. Eye movement behavior is a sensitive index of learning and effects of memory on eye movements have been shown to emerge rapidly (within 500-750ms of stimuli …

Memory-Based Viewing: A Potential Marker Of Pathological Aging, Jenna Blujus

Theses and Dissertations

Markers of cognitive impairment are needed to distinguish normal from pathological aging prior to the onset of clinical symptomology to improve Alzheimer’s disease (AD) treatment or prevention efforts. AD pathology is believed to develop years or even decades prior to diagnosis in medial temporal lobe subregions that provide input to the hippocampus (Braak & Braak, 1991), disrupting the ability of the hippocampus to bind individual elements of an experience to form cohesive memory representations. Eye movement behavior is a sensitive index of learning and effects of memory on eye movements have been shown to emerge rapidly (within 500-750ms of stimuli …

Longitudinal Alzheimer's Degeneration Reflects The Spatial Topography Of Cholinergic Basal Forebrain Projections, Taylor W. Schmitz, Marieke Mur, Meghmik Aghourian, Marc Andre Bedard, R. Nathan Spreng

Brain and Mind Institute Researchers' Publications

© 2018 The Author(s) The cholinergic neurons of the basal forebrain (BF) provide virtually all of the brain's cortical and amygdalar cholinergic input. They are particularly vulnerable to neuropathology in early Alzheimer's disease (AD) and may trigger the emergence of neuropathology in their cortico-amygdalar projection system through cholinergic denervation and trans-synaptic spreading of misfolded proteins. We examined whether longitudinal degeneration within the BF can explain longitudinal cortico-amygdalar degeneration in older human adults with abnormal cerebrospinal fluid biomarkers of AD neuropathology. We focused on two BF subregions, which are known to innervate cortico-amygdalar regions via two distinct macroscopic cholinergic projections. To …

Association Between Alzheimer's Disease And Rural Northeast Tennessee Region Between 2013 And 2015, Sylvester Olubolu Orimaye, Jodi Southerland

Appalachian Student Research Forum

Background: Alzheimer’s disease (AD) is a type of Dementia and a neurodegenerative disease that is characterized by the gradual degrading of both memory and cognitive functions. According to the World Health Organization (WHO), the prevalence of AD is increasing globally. Currently, AD is the sixth leading cause of mortality in the United States. As the ageing population increases in the United States, it is possible that AD will move up the ladder in the top cause of mortality. Although the prevalence of AD in most urban parts of developed nations such as the United States is widely known, little is …

The Famous Names Discrimination Task As A Biomarker Of Alzheimer's Disease Risk: An Erp Study, Elizabeth Rose Paitel

Master's Theses (2009 -)

Current ERP research emphasizes age- and pathology-related declines in neural processing in the form of attenuated amplitudes and prolonged latencies. Notably, there is a gap in the ERP literature regarding neural processing trajectories in the time between healthy young adulthood and clinical MCI/AD samples. fMRI research, however, has demonstrated periods of increased, compensatory activation in healthy, cognitively intact APOE ɛ4 carriers both during resting state and event-related tasks (Bondi, Houston, Eyler, & Brown, 2005; Evans et al., 2014; Filippini et al., 2009; Rao et al., 2015), consistent with compensatory theories of cognitive aging (Cabeza, 2002; Park & Reuter-Lorenz, 2009; Reuter-Lorenz …

Factors Influencing Alzheimer's Disease Healthcare Utilization Patterns In Puerto Rico, Carlamarie Noboa

Walden Dissertations and Doctoral Studies

Alzheimer's disease (AD) is associated with substantial healthcare utilization costs, resulting in a public health priority. In this study, the relationship between the demographic characteristics of age, gender, and type of health insurance; the presence of comorbidities of older Puerto Rican residents diagnosed with AD; and their healthcare utilization patterns (i.e., medical office and emergency room visits and hospital admissions) was examined using Andersen's behavioral model. Data from the 2013 Puerto Rico Health Study was used in this retrospective cohort design study. All AD cases aged -?¥ 60 years were extracted using systematic random sampling. One-way ANOVA-WELCH, Mann-Whitney U test, …

Predictors Of Cognitive Function Among Cognitively Impaired Older African Americans Living In Congregate Residential Settings, Zyra Daffodil Apugan

Dissertations

The purpose of this secondary data analysis was to identify potential psychosocial predictors of cognition, including social support, depression, and functional activity, among older African Americans, ≥ 65 years, with a diagnosis of Alzheimer’s disease and living in congregate residential settings. Guided by the main effect model of social support, this study used existing data from the National Alzheimer’s Coordinating Center Uniform Data Set, an NIH-funded multicenter study. Results showed that on average, the participants (n=56) were 81.7 years of age with 13.8 years of education. All, but six, were married. Bivariate Pearson correlations indicate a moderately strong negative relationship …

Age Drives Distortion Of Brain Metabolic, Vascular And Cognitive Functions, And The Gut Microbiome, Jared D. Hoffman, Ishita Parikh, Stefan J. Green, George Chlipala, Robert P. Mohney, Mignon Keaton, Bjoern Bauer, Anika M. S. Hartz, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in …

The Alzheimer’S Association Dementia Care Coordination Program: A Process Evaluation, Executive Summary, Nina Silverstein, Frank Porell, Pamela Nadash

Nina Silverstein

The Massachusetts/New Hampshire (MA/NH) Chapter of the Alzheimer's Association has long sought ways to systematically increase the number of families who utilize its services and support. According to the Alzheimer’s Association’s 2015 Alzheimer’s Disease Facts and Figures, there are 142,000 individuals living with Alzheimer’s disease in Massachusetts and New Hampshire, and the Alzheimer’s Association estimates that less than 30% of those individuals and their caregivers take advantage of its programs (Alzheimer’s Association, 2015). The MA/NH Chapter recognized that one major barrier to accessing services is a model that relies on families taking the initiative to seek out assistance.

In …

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 …

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 …

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 …

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 …

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 …

The Alzheimer’S Association Dementia Care Coordination Program: A Process Evaluation, Executive Summary, Nina Silverstein, Frank Porell, Pamela Nadash

Gerontology Institute Publications

The Massachusetts/New Hampshire (MA/NH) Chapter of the Alzheimer's Association has long sought ways to systematically increase the number of families who utilize its services and support. According to the Alzheimer’s Association’s 2015 Alzheimer’s Disease Facts and Figures, there are 142,000 individuals living with Alzheimer’s disease in Massachusetts and New Hampshire, and the Alzheimer’s Association estimates that less than 30% of those individuals and their caregivers take advantage of its programs (Alzheimer’s Association, 2015). The MA/NH Chapter recognized that one major barrier to accessing services is a model that relies on families taking the initiative to seek out assistance.

In …

Low Neural Exosomal Levels Of Cellular Survival Factors In Alzheimer's Disease, Edward J. Goetzl, Adam Boxer, Janice B. Schwartz, Erin Abner, Ronald C. Petersen, Bruce L. Miller, Olga D. Carlson, Maja Mustapic, Dimitrios Kapogiannis

Sanders-Brown Center on Aging Faculty Publications

Transcription factors that mediate neuronal defenses against diverse stresses were quantified in plasma neural-derived exosomes of Alzheimer's disease or frontotemporal dementia patients and matched controls. Exosomal levels of low-density lipoprotein receptor-related protein 6, heat-shock factor-1, and repressor element 1-silencing transcription factor all were significantly lower in Alzheimer's disease patients than controls (P < 0.0001). In frontotemporal dementia, the only significant difference was higher levels of repressor element 1-silencing transcription factor than in controls. Exosomal transcription factors were diminished 2-10 years before clinical diagnosis of Alzheimer's disease. Low exosomal levels of survival proteins may explain decreased neuronal resistance to Alzheimer's disease neurotoxic proteins.

A Practical Algorithm For Managing Alzheimer's Disease: What, When, And Why?, Jeffrey L. Cummings, Richard S. Isaacson, Frederick A. Schmitt, Drew M. Velting

Sanders-Brown Center on Aging Faculty Publications

Alzheimer's disease (AD) is the most common form of dementia and its prevalence is increasing. Recent developments in AD management provide improved ways of supporting patients and their caregivers throughout the disease continuum. Managing cardiovascular risk factors, maintaining an active lifestyle (with regular physical, mental and social activity) and following a Mediterranean diet appear to reduce AD risk and may slow cognitive decline. Pharmacologic therapy for AD should be initiated upon diagnosis. All of the currently available cholinesterase inhibitors (ChEIs; donepezil, galantamine, and rivastigmine) are indicated for mild-to-moderate AD. Donepezil (10 and 23 mg/day) and rivastigmine transdermal patch (13.3 mg/24 …

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 …

Receiving While Giving: The Differential Roles Of Receiving Help And Satisfaction With Help On Caregiver Rewards Among Spouses And Adult-Children., Marie Y. Savundranayagam

Marie Y. Savundranayagam

Intracranial Injection Of Gammagard, A Human Ivig, Modulates The Inflammatory Response Of The Brain And Lowers AΒ In App/Ps1 Mice Along A Different Time Course Than Anti-AΒ Antibodies, Tiffany L. Sudduth, Abigail Greenstein, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Gammagard IVIg is a therapeutic approach to treat Alzheimer's disease currently in phase 3 clinical trials. Despite the reported efficacy of the approach the mechanism of action is poorly understood. We have previously shown that intracranial injection of anti-Aβ antibodies into the frontal cortex and hippocampus reveals important information regarding the time course of events once the agent is in the brain. In the current study we compared IVIg, mouse-pooled IgG, and the anti-Aβ antibody 6E10 injected intracranially into the frontal cortex and hippocampus of 7-month-old APP/PS1 mice. We established a time course of events ranging from 1 …

Comprehensive Behavioral Characterization Of An App/Ps-1 Double Knock-In Mouse Model Of Alzheimer's Disease, Scott J. Webster, Adam D. Bachstetter, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: Despite the extensive mechanistic and pathological characterization of the amyloid precursor protein (APP)/presenilin-1 (PS-1) knock-in mouse model of Alzheimer's disease (AD), very little is known about the AD-relevant behavioral deficits in this model. Characterization of the baseline behavioral performance in a variety of functional tasks and identification of the temporal onset of behavioral impairments are important to provide a foundation for future preclinical testing of AD therapeutics. Here we perform a comprehensive behavioral characterization of this model, discuss how the observed behavior correlates with the mechanistic and pathological observations of others, and compare this model with other commonly used …