Geriatrics Commons^™

Healthy Dietary Intake Moderates The Effects Of Age On Brain Iron Concentration And Working Memory Performance, Valentinos Zachariou, Christopher E. Bauer, Elayna R. Seago, Georgia Panayiotou, Edward D. Hall, D. Allan Butterfield, Brian T. Gold

Neuroscience Faculty Publications

Age-related brain iron accumulation is linked with oxidative stress, neurodegeneration and cognitive decline. Certain nutrients can reduce brain iron concentration in animal models, however, this association is not well established in humans. Moreover, it remains unknown if nutrition can moderate the effects of age on brain iron concentration and/or cognition. Here, we explored these issues in a sample of 73 healthy older adults (61-86 years old), while controlling for several factors such as age, gender, years of education, physical fitness and alcohol-intake. Quantitative susceptibility mapping was used for assessment of brain iron concentration and participants performed an N-Back paradigm 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 …

Physical Activity Interventions For Older Adults In The Age Of Covid-19 And Beyond, Rachel N. Bragg, K. Jason J. Crandall

Topics in Exercise Science and Kinesiology

Topics in Exercise Science and Kinesiology Volume 2: Issue 1, Article 6, 2021. As the coronavirus (COVID-19) pandemic continues, it is important to understand why older adults are at higher risk for more severe morbidity and higher mortality compared to younger age groups. At the same time, there is a growing body of evidence suggesting physical activity and exercise can have positive benefits for older adults’ health. Point of application #1: The first step in keeping older adults active is motivating them to adhere to a structured program either at home, in a community setting, or in a long-term care …

Social Engagement Of Nursing Home Residents: A Comparison Of Two Observation Methods, Annika Gabbard

Masters Theses & Specialist Projects

In Kentucky, low levels of physical activity and social engagement negatively impact health. This problem led to the creation of Bingocize®, an exercise program that combines the game of Bingo with intermittent exercises in a group setting to increase levels of positive affect, physical health, and, the focus of this study, social engagement. Since clear benefits of social engagement have been established, measurement and documentation of this behavior can assist in determining the level of potential benefit from Bingocize®. The purpose of this study was to compare the opinions of healthcare workers who have experience with Bingocize® on two measures …

Broad Kinase Inhibition Mitigates Early Neuronal Dysfunction In Tauopathy, Shon A. Koren, Matthew J. Hamm, Ryan Cloyd, Sarah N. Fontaine, Emad Chishti, Chiara Lanzillotta, Jennifer Rodriguez-Rivera, Alexandria Ingram, Michelle Bell, Sara M. Galvis-Escobar, Nicholas Zulia, Fabio Di Domenico, Duc Duong, Nicholas T. Seyfried, David K. Powell, Moriel Vandsburger, Tal Frolinger, Anika M. S. Hartz, John Koren Iii, Jeffrey M. Axten, Nicholas J. Laping, Jose F. Abisambra

Sanders-Brown Center on Aging Faculty Publications

Tauopathies are a group of more than twenty known disorders that involve progressive neurodegeneration, cognitive decline and pathological tau accumulation. Current therapeutic strategies provide only limited, late-stage symptomatic treatment. This is partly due to lack of understanding of the molecular mechanisms linking tau and cellular dysfunction, especially during the early stages of disease progression. In this study, we treated early stage tau transgenic mice with a multi-target kinase inhibitor to identify novel substrates that contribute to cognitive impairment and exhibit therapeutic potential. Drug treatment significantly ameliorated brain atrophy and cognitive function as determined by behavioral testing and a sensitive imaging …

Arginase 1 Insufficiency Precipitates Amyloid-Β Deposition And Hastens Behavioral Impairment In A Mouse Model Of Amyloidosis, Chao Ma, Jerry B. Hunt, Maj-Linda B. Selenica, Awa Sanneh, Leslie A. Sandusky-Beltran, Mallory Watler, Rana Daas, Andrii Kovalenko, Huimin Liang, Devon Placides, Chuanhai Cao, Xiaoyang Lin, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Alzheimer’s disease (AD) includes several hallmarks comprised of amyloid-β (Aβ) deposition, tau neuropathology, inflammation, and memory impairment. Brain metabolism becomes uncoupled due to aging and other AD risk factors, which ultimately lead to impaired protein clearance and aggregation. Increasing evidence indicates a role of arginine metabolism in AD, where arginases are key enzymes in neurons and glia capable of depleting arginine and producing ornithine and polyamines. However, currently, it remains unknown if the reduction of arginase 1 (Arg1) in myeloid cell impacts amyloidosis. Herein, we produced haploinsufficiency of Arg1 by the hemizygous deletion in myeloid cells using Arg1 …

Lat1 Protein Content Increases Following 12 Weeks Of Resistance Exercise Training In Human Skeletal Muscle, Paul A. Roberson, Christopher Brooks Mobley, Matthew A. Romero, Cody T. Haun, Shelby C. Osburn, Petey W. Mumford, Christopher G. Vann, Rory A. Greer, Arny A. Ferrando, Michael D. Roberts

Physiology Faculty Publications

Introduction: Amino acid transporters are essential for cellular amino acid transport and promoting protein synthesis. While previous literature has demonstrated the association of amino acid transporters and protein synthesis following acute resistance exercise and amino acid supplementation, the chronic effect of resistance exercise and supplementation on amino acid transporters is unknown. The purpose herein was to determine if amino acid transporters and amino acid metabolic enzymes were related to skeletal muscle hypertrophy following resistance exercise training with different nutritional supplementation strategies.

Methods: 43 college-aged males were separated into a maltodextrin placebo (PLA, n = 12), leucine (LEU, n = 14), …

Neither “Post-War” Nor Post-Pregnancy Paranoia: How America’S War On Drugs Continues To Perpetuate Disparate Incarceration Outcomes For Pregnant, Substance-Involved Offenders, Becca S. Zimmerman

Pitzer Senior Theses

This thesis investigates the unique interactions between pregnancy, substance involvement, and race as they relate to the War on Drugs and the hyper-incarceration of women. Using ordinary least square regression analyses and data from the Bureau of Justice Statistics’ 2016 Survey of Prison Inmates, I examine if (and how) pregnancy status, drug use, race, and their interactions influence two length of incarceration outcomes: sentence length and amount of time spent in jail between arrest and imprisonment. The results collectively indicate that pregnancy decreases length of incarceration outcomes for those offenders who are not substance-involved but not evenhandedly -- benefitting white …

How Does Direct Volunteering Affect The Onset Of Alzheimer’S Dementia In Elderly Patients With Preexisting Cardiac Comorbidities?, Sneha R. Gade

UROP Posters

Alzheimer's Dementia is a disease that affects memory, thinking, and behavior. The Alzheimer's Association reported Alzheimer's as the sixth-leading cause of death in the United States, and a cure does not exist. Donepezil, a cholinesterase inhibitor drug, is frequently prescribed to treat Alzheimer's disease. Still, patients must continuously take the medication for years to receive any measurable improvement in quality of life after developing Alzheimer's Dementia. Further, research shows prolonged use of Donepezil can lead to other health problems, such as QTc prolongation, for cardiac disease patients. Therefore, the effectiveness of non-drug interventions, such as volunteering to prevent the disease's …

Cortical Iron Disrupts Functional Connectivity Networks Supporting Working Memory Performance In Older Adults, Valentinos Zachariou, Christopher E. Bauer, Elayna R. Seago, Flavius D. Raslau, David K. Powell, Brian T. Gold

Neuroscience Faculty Publications

Excessive brain iron negatively affects working memory and related processes but the impact of cortical iron on task-relevant, cortical brain networks is unknown. We hypothesized that high cortical iron concentration may disrupt functional circuitry within cortical networks supporting working memory performance. Fifty-five healthy older adults completed an N-Back working memory paradigm while functional magnetic resonance imaging (fMRI) was performed. Participants also underwent quantitative susceptibility mapping (QSM) imaging for assessment of non-heme brain iron concentration. Additionally, pseudo continuous arterial spin labeling scans were obtained to control for potential contributions of cerebral blood volume and structural brain images were used to control …

Distribution Of Microglial Phenotypes As A Function Of Age And Alzheimer's Disease Neuropathology In The Brains Of People With Down Syndrome, Alessandra C. Martini, Alex M. Helman, Katie L. Mccarty, Ira T. Lott, Eric Doran, Frederick A. Schmitt, Elizabeth Head

Sanders-Brown Center on Aging Faculty Publications

Introduction: Microglial cells play an important role in the development of Alzheimer's disease (AD). People with Down syndrome (DS) inevitably develop AD neuropathology (DSAD) by 40 years of age. We characterized the distribution of different microglial phenotypes in the brains of people with DS and DSAD.

Methods: Autopsy tissue from the posterior cingulate cortex (PCC) from people with DS, DSAD, and neurotypical controls was immunostained with the microglial marker Iba1 to assess five microglia morphological types.

Results: Individuals with DS have more hypertrophic microglial cells in their white matter. In the gray matter, individuals with DSAD had significantly fewer ramified …

Tdp-43 Mediated Blood-Brain Barrier Permeability And Leukocyte Infiltration Promote Neurodegeneration In A Low-Grade Systemic Inflammation Mouse Model, Frank Zamudio, Anjanet R. Loon, Shayna Smeltzer, Khawla Benyamine, Nanda K. Navalpur Shanmugam, Nicholas J. F. Stewart, Daniel C. Lee, Kevin Nash, Maj-Linda B. Selenica

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Neuronal cytoplasmic inclusions containing TAR DNA-binding protein 43 (TDP-43) are a neuropathological feature of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's Disease (AD). Emerging evidence also indicates that systemic inflammation may be a contributor to the pathology progression of these neurodegenerative diseases.

METHODS: To investigate the role of systemic inflammation in the progression of neuronal TDP-43 pathology, AAV9 particles driven by the UCHL1 promoter were delivered to the frontal cortex of wild-type aged mice via intracranial injections to overexpress TDP-43 or green fluorescent protein (GFP) in corticospinal motor neurons. Animals were then subjected …

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 …

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 …

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 …

Reliability And Validity Of An Assessment Of Engagement In Nursing Home Residents During Bingocize®, Elizabeth Batson Apelt

Masters Theses & Specialist Projects

Research suggests nursing home residents are often socially isolated and physically inactive despite overwhelming evidence that both social engagement and physical activity are crucial for healthy aging (Jones, Sung, & Moyle, 2018; Yen & Lin, 2018; Ice, 2002; Jansson et al., 2017). Bingocize® is a program that combines exercise and the game of Bingo to improve the quality of life, physical health, and social engagement of certified nursing facility (CNF) residents. The purpose of this study is to determine the level of social engagement displayed by CNF residents during Bingocize® using the Fun and Social Engagement Evaluation (FUSE). Reliability and …

A Retrospective Matched-Cohort Study Of 3994 Lower Extremity Wounds Of Multiple Etiologies Across 644 Institutions Comparing A Bioactive Human Skin Allograft, Theraskin, Plus Standard Of Care, To Standard Of Care Alone, Geoff C Gurtner, Aimee D Garcia, Katie Bakewell, Jason B Alarcon

Faculty, Staff and Students Publications

Most chronic wounds are related to comorbidities, for which no clinical trials are performed. This retrospective propensity matched-cohort study examined data from 2 074 000 lower extremity wounds across 644 institutions to determine the effectiveness of TheraSkin plus standard of care (SOC; n = 1997) versus SOC alone (n = 1997). Multivariate modelling comparing outcomes such as healing rates, percent area reductions (PARs), amputations, recidivism, treatment completion, and medical transfers were evaluated. A higher proportion of wounds in the treatment group compared with the controls were more likely to close (68.3% versus 60.3%), particularly wounds with exposed structures (64% versus …

Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha

Neurology Faculty Publications

BACKGROUND: Disparate research sites using identical or near-identical magnetic resonance imaging (MRI) acquisition techniques often produce results that demonstrate significant variability regarding volumetric quantification of white matter hyperintensities (WMH) in the aging population. The sources of such variability have not previously been fully explored.

NEW METHOD: 3D FLAIR sequences from a group of randomly selected aged subjects were analyzed to identify sources-of-variability in post-acquisition processing that can be problematic when comparing WMH volumetric data across disparate sites. The methods developed focused on standardizing post-acquisition protocol processing methods to develop a protocol with less than 0.5% inter-rater variance.

RESULTS: A series …

An Animal-Assisted Intervention Study In The Nursing Home: Lessons Learned, Lonneke G. J. A. Schuurmans, Inge Noback, Jos M. G. A. Schols, Marie-Jose Enders-Slegers

People and Animals: The International Journal of Research and Practice

AAI studies in the nursing home pose a specific set of challenges. In this article the practical and ethical issues encountered during a Dutch psychogeriatric nursing home AAI study are addressed with the aim of sharing our experiences for future researchers as well as AAI practitioners in general.

In our study we compared three groups of clients with dementia who participated in group sessions of either visiting dog teams, visiting FurReal Friend robot animals, or visiting students (control group) and monitored the effect on social interaction and neuropsychiatric symptoms through video analysis and questionnaires. We encountered the following four categories …

Association Of Fish Oil And Physical Activity On Mobility Disability In Older Adults, Anoop T. Balachandran

Publications and Research

Purpose: This study aimed to examine whether long-term fish oil (FO) supplementation is associated with a lower risk of mobility disability and enhances benefits of physical activity (PA). Methods: A total of 1635 sedentary adults age 70 to 89 yr from the Lifestyle Interventions and Independence for Elders single-blinded randomized,multicenter clinical trial, which compared a structured PA program to a health education program. Primary outcome was incident major mobility disability (MMD), defined by loss of ability to walk 400 m, measured every 6 months for an average of 2.6 yr. Secondary outcomes included persistent mobility disability, Short Physical Performance Battery, …

Distinct Patterns Of Default Mode And Executive Control Network Circuitry Contribute To Present And Future Executive Function In Older Adults, Christopher A. Brown, Frederick A. Schmitt, Charles D. Smith, Brian T. Gold

Neuroscience Faculty Publications

Executive function (EF) performance in older adults has been linked with functional and structural profiles within the executive control network (ECN) and default mode network (DMN), white matter hyperintensities (WMH) burden and levels of Alzheimer's disease (AD) pathology. Here, we simultaneously explored the unique contributions of these factors to baseline and longitudinal EF performance in older adults. Thirty-two cognitively normal (CN) older adults underwent neuropsychological testing at baseline and annually for three years. Neuroimaging and AD pathology measures were collected at baseline. Separate linear regression models were used to determine which of these variables predicted composite EF scores at baseline …

A 24-Week Double-Blind Placebo-Controlled Study Of The Efficacy And Safety Of The Ampa Modulator S47445 In Patients With Mild To Moderate Alzheimer's Disease And Depressive Symptoms, Eileen M. Bulger, Sylvie Gouttefangeas, Sylvie Bretin, Stéphanie Galtier, Philippe Robert, Vjera Holthoff-Detto, Jeffrey Cummings, Maria Pueyo

School of Medicine Faculty Research

Introduction S47445 is a novel positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors that may emerge as a favorable candidate for the symptomatic treatment of cognitive and depressive disorders in patients suffering from Alzheimer's disease (AD) of mild to moderate severity and with depressive symptoms. Methods For this double-blind, placebo-controlled 24-week phase II trial, 520 outpatients aged between 55 and 85 years, with probable AD at mild to moderate stages (a Mini-Mental State Examination score of 24-15 inclusive) and exhibiting depressive symptoms (Cornell Scale for Depression in Dementia [CSDD] ≥ 8) were recruited in twelve countries and randomized to 3 doses …

Visual And Verbal Serial List Learning In Patients With Statistically-Determined Mild Cognitive Impairment., Victor Wasserman, Sheina Emrani, Emily F Matusz, David Miller, Kelly Davis Garrett, Katherine A Gifford, Timothy J Hohman, Angela L Jefferson, Rhoda Au, Rod Swenson, David J Libon, Consortium For Clinical And Epidemiological Neuropsychological Data Analysis (Cenda).

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Background and Objective: Prior research with patients with mild cognitive impairment (MCI) suggests that visual versus verbal episodic memory test performance may be more sensitive to emergent illness. However, little research has examined visual versus verbal episodic memory performance as related to MCI subtypes.

Research Design and Methods: Patients were diagnosed with non-MCI, amnestic MCI (aMCI), and combined mixed/dysexecutive MCI (mixed/dys MCI). Visual and verbal episodic memory were assessed with the Brief Visuospatial Memory Test-Revised (BVMT-R) and the 12-word Philadelphia (repeatable) Verbal Learning Test (P[r]VLT), respectively.

Results: BVMT-R and P(r)VLT scores yielded similar between-group patterns of performance. Non-MCI patients scored …

Validation Of A 5-Minute Vpc Test To Assess And Compare Cognitively Intact Individuals And Individuals With Cognitive Impairments, Spencer Smith

Graduate Theses and Dissertations

The prevalence of cognitive impairments in the older adult population is growing. Finding treatment solutions to impede a cognitive decline can possibly lead to fewer cases of mild cognitive impairment, dementia, and Alzheimer’s disease. A Visual Paired Comparison (VPC) could serve as a tool to predict, monitor, and regulate people who are susceptible to a cognitive decline. The purpose of this study was to 1) to determine the validity of the Neurotrack 5-minute VPC test with the Neurotrack 30-minute VPC test, 2) to determine the test-retest reliability of the Neurotrack 5-minute VPC test, 3) to compare Neurotrack 5-minute VPC scores …

Perceptions Of Risk Of Health Disparities Amid Previously Identified Political Corruption And Ageism In Slovakia, Marta N. Lukacovic, Deborah D. Sellnow-Richmond, Monika Durechova

International Crisis and Risk Communication Conference

This study examines the role of traditional versus new media’s impact on citizens’ perceptions of risk within elder care. We analyzed survey data from 112 Slovak citizens regarding their social network activity and perceptions of corruption, ageism, and health disparities in the Slovak elder care system. Previous research (Lukacovic, Sellnow-Richmond, & Durechova, under contract) identified three prominent sociopolitical issues present in the Slovak medical system among Slovak UGC discourse regarding Slovak healthcare inequity: corruption, threats to dignity, and discrimination. Here, we examined the extent to which social media users perceive the prevalence and subsequent risk of experiencing health disparities within …

Manganese-Enhanced Magnetic Resonance Imaging: Overview And Central Nervous System Applications With A Focus On Neurodegeneration, Ryan A. Cloyd, Shon A. Koren, Jose F. Abisambra

Physiology Faculty Publications

Manganese-enhanced magnetic resonance imaging (MEMRI) rose to prominence in the 1990s as a sensitive approach to high contrast imaging. Following the discovery of manganese conductance through calcium-permeable channels, MEMRI applications expanded to include functional imaging in the central nervous system (CNS) and other body systems. MEMRI has since been employed in the investigation of physiology in many animal models and in humans. Here, we review historical perspectives that follow the evolution of applied MRI research into MEMRI with particular focus on its potential toxicity. Furthermore, we discuss the more current in vivo investigative uses of MEMRI in CNS investigations and …

Hyperhomocysteinemia As A Risk Factor For Vascular Contributions To Cognitive Impairment And Dementia, Brittani R. Price, Donna M. Wilcock, Erica M. Weekman

Physiology Faculty Publications

Behind only Alzheimer’s disease, vascular contributions to cognitive impairment and dementia (VCID) is the second most common cause of dementia, affecting roughly 10–40% of dementia patients. While there is no cure for VCID, several risk factors for VCID, such as diabetes, hypertension, and stroke, have been identified. Elevated plasma levels of homocysteine, termed hyperhomocysteinemia (HHcy), are a major, yet underrecognized, risk factor for VCID. B vitamin deficiency, which is the most common cause of HHcy, is common in the elderly. With B vitamin supplementation being a relatively safe and inexpensive therapeutic, the treatment of HHcy-induced VCID would seem straightforward; however, …

Astrocyte Activation And The Calcineurin/Nfat Pathway In Cerebrovascular Disease, Susan D. Kraner, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Calcineurin (CN) is a Ca²⁺/calmodulin-dependent protein phosphatase with high abundance in nervous tissue. Though enriched in neurons, CN can become strongly induced in subsets of activated astrocytes under different pathological conditions where it interacts extensively with the nuclear factor of activated T cells (NFATs). Recent work has shown that regions of small vessel damage are associated with the upregulation of a proteolized, highly active form of CN in nearby astrocytes, suggesting a link between the CN/NFAT pathway and chronic cerebrovascular disease. In this Mini Review article, we discuss CN/NFAT signaling properties in the context of vascular disease and …

Neuroimaging Biomarkers Of Mtor Inhibition On Vascular And Metabolic Functions In Aging Brain And Alzheimer’S Disease, Jennifer Lee, Lucille M. Yanckello, David Ma, Jared D. Hoffman, Ishita Parikh, Scott Thalman, Bjoern Bauer, Anika M. S. Hartz, Fahmeed Hyder, Ai-Ling Lin

Pharmacology and Nutritional Sciences Faculty Publications

The mechanistic target of rapamycin (mTOR) is a nutrient sensor of eukaryotic cells. Inhibition of mechanistic mTOR signaling can increase life and health span in various species via interventions that include rapamycin and caloric restriction (CR). In the central nervous system, mTOR inhibition demonstrates neuroprotective patterns in aging and Alzheimer’s disease (AD) by preserving mitochondrial function and reducing amyloid beta retention. However, the effects of mTOR inhibition for in vivo brain physiology remain largely unknown. Here, we review recent findings of in vivo metabolic and vascular measures using non-invasive, multimodal neuroimaging methods in rodent models for brain aging and AD. …

Ca2+, Astrocyte Activation And Calcineurin/Nfat Signaling In Age-Related Neurodegenerative Diseases, Pradoldej Sompol, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Mounting evidence supports a fundamental role for Ca²⁺ dysregulation in astrocyte activation. Though the activated astrocyte phenotype is complex, cell-type targeting approaches have revealed a number of detrimental roles of activated astrocytes involving neuroinflammation, release of synaptotoxic factors and loss of glutamate regulation. Work from our lab and others has suggested that the Ca²⁺/calmodulin dependent protein phosphatase, calcineurin (CN), provides a critical link between Ca²⁺ dysregulation and the activated astrocyte phenotype. A proteolyzed, hyperactivated form of CN appears at high levels in activated astrocytes in both human tissue and rodent tissue around regions of amyloid and …