Geriatrics Commons^™

Analysis Of Genes (Tmem106b, Grn, Abcc9, Kcnmb2, And Apoe) Implicated In Risk For Late-Nc And Hippocampal Sclerosis Provides Pathogenetic Insights: A Retrospective Genetic Association Study, Adam J. Dugan, Peter T. Nelson, Yuriko Katsumata, Lincoln M. P. Shade, Kevin L. Boehme, Merilee A. Teylan, Matthew D. Cykowski, Shubhabrata Mukherjee, John S. K. Kauwe, Timothy J. Hohman, Julie A. Schneider, Alzheimer’S Disease Genetics Consortium, David W. Fardo

Biostatistics Faculty Publications

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is the most prevalent subtype of TDP-43 proteinopathy, affecting up to 1/3rd of aged persons. LATE-NC often co-occurs with hippocampal sclerosis (HS) pathology. It is currently unknown why some individuals with LATE-NC develop HS while others do not, but genetics may play a role. Previous studies found associations between LATE-NC phenotypes and specific genes: TMEM106B, GRN, ABCC9, KCNMB2, and APOE. Data from research participants with genomic and autopsy measures from the National Alzheimer’s Coordinating Center (NACC; n = 631 subjects included) and the Religious Orders Study and Memory …

Barriers And Benefits Experienced In Qualitative Geriatric Emergency Care Research During The Covid-19 Era, James D. Van Oppen, Emma Regen, Kay Phelps, Timothy J. Coats, Jose M. Valderas, Simon P. Conroy, Nicola Mackintosh

Journal of Geriatric Emergency Medicine

No abstract provided.

Exercise Intolerance In Older Adults With Heart Failure With Preserved Ejection Fraction: Jacc State-Of-The-Art Review, Ambarish Pandey, Sanjiv J Shah, Javed Butler, Dean L Kellogg, Gregory D Lewis, Daniel E Forman, Robert J Mentz, Barry A Borlaug, Marc A Simon, Julio A Chirinos, Roger A Fielding, Elena Volpi, Anthony J A Molina, Mark J Haykowsky, Flora Sam, Bret H Goodpaster, Alain G Bertoni, Jamie N Justice, James P White, Jingzhone Ding, Scott L Hummel, Nathan K Lebrasseur, George E Taffet, Iraklis I Pipinos, Dalane Kitzman

Faculty, Staff and Students Publications

Exercise intolerance (EI) is the primary manifestation of chronic heart failure with preserved ejection fraction (HFpEF), the most common form of heart failure among older individuals. The recent recognition that HFpEF is likely a systemic, multiorgan disorder that shares characteristics with other common, difficult-to-treat, aging-related disorders suggests that novel insights may be gained from combining knowledge and concepts from aging and cardiovascular disease disciplines. This state-of-the-art review is based on the outcomes of a National Institute of Aging-sponsored working group meeting on aging and EI in HFpEF. We discuss aging-related and extracardiac contributors to EI in HFpEF and provide the …

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

Sanders-Brown Center on Aging Faculty Publications

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

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

Neuroscience Faculty Publications

No abstract provided.

Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude C. Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson

Physiology Faculty Publications

BACKGROUND: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer's disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.

METHODS: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.

RESULTS: Single-cell …

Can An Emergency Department Adequately Address An Older Adult Who Has Complex Needs?, Rami Tarabay, Adam Perry, Riwa Al Aridi, Michael Malone

Journal of Geriatric Emergency Medicine

Older adults account for a considerable percentage of all emergency departments (ED) patient encounters. Those with very complex needs or multiple co-morbid conditions often have lengthy ED evaluations culminating in admission, many of which are considered potentially avoidable. Provider and process elements can evolve to create efficient and more comprehensive geriatric assessments in ED. This paper describes an older adult with acute on chronic symptoms admitted through the ED to the Acute Care for Elders (ACE) inpatient unit. We illustrate how elements of the ACE model, when applied in the ED, may avoid hospitalization. We review the Domain Management Model …

Delirium In Frail Older Adults, Min Ji Kwak

Faculty, Staff and Student Publications

Delirium and frailty are prevalent geriatric syndromes and important public health issues among older adults. The prevalence of delirium among hospitalized older adults ranges from 15% to 75%, while that of frailty ranges from 12% to 24%. The exact pathophysiology of these two conditions has not been clearly identified, although several hypotheses have been proposed. However, these conditions are considered to be multifactorial in etiology and are associated with inflammation related to aging, alterations in vascular systems, genetics, and nutritional deficiency. Furthermore, clinically, they are significantly associated with frailty, which increases the risk of delirium by almost two- to three-fold …

Micrornas As Biomarkers For Predicting Complications Following Aneurysmal Subarachnoid Hemorrhage, Wang-Xia Wang, Joe E. Springer, Kevin W. Hatton

Sanders-Brown Center on Aging Faculty Publications

Aneurysmal subarachnoid hemorrhage (aSAH) is a high mortality hemorrhagic stroke that affects nearly 30,000 patients annually in the United States. Approximately 30% of aSAH patients die during initial hospitalization and those who survive often carry poor prognosis with one in five having permanent physical and/or cognitive disabilities. The poor outcome of aSAH can be the result of the initial catastrophic event or due to the many acute or delayed neurological complications, such as cerebral ischemia, hydrocephalus, and re-bleeding. Unfortunately, no effective biomarker exists to predict or diagnose these complications at a clinically relevant time point when neurologic injury can be …

Intra-Arterial Combination Therapy For Experimental Acute Ischemic Stroke, Michael E. Maniskas, Jill M. Roberts, Amanda A. Gorman, Gregory J. Bix, Justin F. Fraser

Neurosurgery Faculty Publications

Acute ischemic stroke continues to devastate millions of individuals worldwide. Current treatments work to restore blood flow but not rescue affected tissue. Our goal was to develop a combination of neuroprotective agents administered intra-arterially following recanalization to target ischemic tissue. Using C57Bl/6J male mice, we performed tandem transient ipsilateral middle cerebral/common carotid artery occlusion, followed by immediate intra-arterial pharmacotherapy administration through a standardized protocol. Two pharmacotherapy agents, verapamil and lubeluzole, were selected based on their potential to modulate different aspects of the ischemic cascade; verapamil, a calcium channel blocker, works in an acute fashion blocking L-type calcium channels, whereas lubeluzole, …

Cognitive And Behavioral Domains That Reliably Differentiate Normal Aging And Dementia In Down Syndrome, Jordan P. Harp, Lisa M. Koehl, Kathryn L. Van Pelt, Christy L. Hom, Eric Doran, Elizabeth Head, Ira T. Lott, Frederick A. Schmitt

Neurology Faculty Publications

Primary care integration of Down syndrome (DS)-specific dementia screening is strongly advised. The current study employed principal components analysis (PCA) and classification and regression tree (CART) analyses to identify an abbreviated battery for dementia classification. Scale- and subscale-level scores from 141 participants (no dementia n = 68; probable Alzheimer’s disease n = 73), for the Severe Impairment Battery (SIB), Dementia Scale for People with Learning Disabilities (DLD), and Vineland Adaptive Behavior Scales—Second Edition (Vineland-II) were analyzed. Two principle components (PC1, PC2) were identified with the odds of a probable dementia diagnosis increasing 2.54 times per PC1 unit increase and by …

Caregiver Support In The Emergency Department, Candace Kim, Dawn Butler, Todd C. James

Journal of Geriatric Emergency Medicine

Caregiver support in the emergency department can lead to improved patient care, decreased suffering and lower costs. Identifying caregivers and inviting them onto the healthcare team enhances care. It is useful to document risk factors for caregiver stress and provide resources. The Kingston Caregiver Stress Scale is a tool suitable for assessing needs of caregivers. Multiple health professionals in the emergency department can be utilized to support caregivers.

Unmet Needs And Social Challenges For Older Adults During And After The Covid-19 Pandemic: An Opportunity To Improve Care, Alyssa Elman, Daniel Baek, Elaine Gottesman, Michael E. Stern, Mary R. Mulcare, Amy Shaw, Morgan Pearman, Michelle Sullivan, Sunday Clark, Timothy F. Platts-Mills, Rahul Sharma, Tony Rosen

Journal of Geriatric Emergency Medicine

Many older adults have unmet needs and social challenges that can negatively impact their health and well-being, particularly during and after the COVID pandemic. These include social isolation, inadequate care or assistance with their daily activities, food insecurity, housing insecurity, poverty, and abuse/neglect/exploitation. An ED visit provides a unique and critical opportunity to identify these issues and initiate intervention for these vulnerable older adults. By assessing for unmet needs and social challenges, considering a team-based approach as to how they may be ameliorated, using online tools, and integrating telehealth and EMS, ED providers have the potential to dramatically improve …

Management Of Fall Patients – What Should Be Done For Emergency Department Fall Patients?, Katherine Selman, Christine Binkley, Katherine Davenport, Shan W. Lliu, Maura Kennedy

Journal of Geriatric Emergency Medicine

Falls are the leading cause of injury-related emergency visits in older adults, translating into an estimated 3 million ED visits and 32,000 deaths from fall-related injuries annually in the United States. Falls subsequently result in diminished functional ability and higher risk for future falls and mortality. Despite this, ED clinicians focus primarily on injuries that result from a fall and often defer the modifiable causes of the fall and future fall prevention to outpatient providers. We review two articles that address the feasibility of performing interventions from the ED and the efficacy of a multifactorial fall intervention program.

Community-Dwelling Older Adult Fall Prevention Improvement Project, Evan Edminster Bsn, Rn, Cfrn, Tcrn, Cen, Nhdp-Bc

Master's Projects and Capstones

Abstract

Problem: Ground-level falls among community-dwelling adults 60 years and older are significant and contribute to adverse health outcomes such as fractures, functional decline, disability, and death. Additionally, falls among community-dwelling older adults are the number one mechanism of injury seen at a Northern California Level II trauma center. Falls often lead to post-fall fear, activity restriction, and physical deconditioning, further compounding fall risk.

Context: When trauma centers provide targeted outreach and screening for unmanaged health risks such as falls, they reduce unnecessary disability and premature death in the local population. Reducing total fall victim numbers and fall recidivism also …

Macrocyclic Immunoproteasome Inhibitors As A Potential Therapy For Alzheimer's Disease, Min Jae Lee, Deepak Bhattarai, Hyeryung Jang, Ahreum Baek, In Jun Yeo, Seongsoo Lee, Zachary Miller, Sukyeong Lee, Jin Tae Hong, Dong-Eun Kim, Wooin Lee, Kyung Bo Kim

Faculty, Staff and Students Publications

Previously, we reported that immunoproteasome (iP)-targeting linear peptide epoxyketones improve cognitive function in mouse models of Alzheimer's disease (AD) in a manner independent of amyloid β. However, these compounds' clinical prospect for AD is limited due to potential issues, such as poor brain penetration and metabolic instability. Here, we report the development of iP-selective macrocyclic peptide epoxyketones prepared by a ring-closing metathesis reaction between two terminal alkenes attached at the P2 and P3/P4 positions of linear counterparts. We show that a lead macrocyclic compound DB-60 (

Using The 4m Model To Screen Geriatric Patients In The Emergency Department, Martinus Megalla, Roopa Avula, Christopher Manners, Portia Chinnery, Lindsey Perrella, Douglas Finefrock

Journal of Geriatric Emergency Medicine

Several models of specialized geriatric care in the Emergency Department (ED) have been developed since the American College of Emergency Physicians (ACEP) began accrediting geriatric EDs in 2018. There is considerable variability in terms of both design and efficacy in regard to screening older patients in the ED and determining proper interventions The John A. Hartford Foundation and Institute for Healthcare Improvement (IHI) have developed the 4M Model for Creating Age-Friendly Health Systems which aims to provide high quality care to older patients by addressing four critical elements: Mentation, Mobility, Medication, What Matters. This article describes a screening tool for …

An Investigation Of New Medications Initiation During Ambulatory Care Visits In Patients With Dementia, Alexandra Wallem, Ashley I. Martinez, Lauren Vickers, Michael Singleton, Daniela C. Moga

Pharmacy Practice and Science Faculty Publications

Background
There is currently insufficient data describing how new medications are provided to older adult ambulatory patients with dementia in the United States (US).

Objectives
To describe characteristics of ambulatory care visits for adults ≥ 65 years old and investigate differences in prescribing of new medications between patients with and without dementia.

Methods
We conducted a population-based cross-sectional study using the 2016 National Ambulatory Medical Care Survey (NAMCS) in the US. Non-perioperative ambulatory care visits of patients ≥ 65 years old with sampling weights were used to provide national estimates of visits. Baseline characteristics were compared between visits for patients …

“I’M Not Staying In The Hospital Tonight”: How Emergency Departments Can Leverage Health And Social Services At Home To Support Care Transitions For Older Patients, Emily Franzosa, Ula Hwang, Maya Genovesi, Orna Intrator, Thomas Edes, Michael Malone

Journal of Geriatric Emergency Medicine

When hospital admission is less than desirable and sending a patient home alone feels unsafe, connecting patients to health and social services at home are a valuable third option for emergency providers. Coordinating home support services from the ED is effective care delivery and aligns with health systems’ goals of decreasing avoidable admissions, and developing capacity to assess and refer patients to home support from the ED is part of good emergency care. Change also doesn’t have to happen overnight. Taking small steps now to improve older patients' transitions to home can help EDs build toward high-quality, patient-centered care for …

Six-Month Health Outcomes In Elderly Patients Post Covid-19 (Shoe-P), Nikhil Sharma, Neti N. Vora Md

Research Scholars

No abstract provided.

A Preliminary Evaluation Of The Behavioral Gerontology Staff Training Protocols, Minyoung Kim

Masters Theses

Staff training in aging settings is integral to ensuring quality services, and such training has traditionally been conducted in person. With the COVID-19 outbreak, there is a need for innovative approaches to training that reduce exposure for trainers and staff. However, the efficacy of such an approach has not yet been demonstrated. To prevent the waste of staff resources at long-term care facilities, this study evaluates the efficacy of behavioral gerontology staff training protocols as a form of telehealth by utilizing graduate and undergraduate students as pilot participants. We use an additive concurrent multiple-probe design across participants to evaluate the …

Prevention Of Falls In Hospital: Audit Report From A Tertiary Care Hospital Of Pakistan, Anum Sadruddin Pidani, Tashfeen Ahmad, Nasreen Panjwani, Shahryar Noordin

Department of Surgery Docs

Objective: The study aims to assess the fall incidents in past 5 years and fall assessment practices at the Aga Khan University Hospital, Karachi.
Methods: We performed a single-center retrospective audit at Aga Khan University Hospital from October 2019 to December 2019. A list of all patients admitted to Aga Khan University Hospital under the Musculoskeletal and Sports Medicine Service Line was obtained using the Hospital Information Management System (HIMS) from Jan 2017 to June 2018. Data including fall assessment scores was collected retrospectively from medical record files.
Results: A total of 1499 patients were admitted during this time period, …

An Overview Of Individualized Management Of Neuropsychiatric Symptoms In Dementia, Megan B. Knoll

Theses and Graduate Projects

Background: It is estimated that about 11% of adults 65 and older have dementia in the United States. Neuropsychiatric symptoms are common in the presentation of dementia. These symptoms often result in increased morbidity and mortality, negative patient outcomes, caregiver burden, institutionalized care, and diminished quality of life. The focus of this paper is to analyze the therapeutic effectiveness of nonpharmacologic interventions in the management of neuropsychiatric symptoms of dementia.

Methods: A literature review was conducted to critique current evidence on the use of nonpharmacologic interventions in managing neuropsychiatric symptoms in older adults with dementia. Searches were performed using PubMed, …

White Matter Hyperintensity Volume And Location: Associations With Wm Microstructure, Brain Iron, And Cerebral Perfusion, Christopher E. Bauer, Valentinos Zachariou, Elayna R. Seago, Brian T. Gold

Neuroscience Faculty Publications

Cerebral white matter hyperintensities (WMHs) represent macrostructural brain damage associated with various etiologies. However, the relative contributions of various etiologies to WMH volume, as assessed via different neuroimaging measures, is not well-understood. Here, we explored associations between three potential early markers of white matter hyperintensity volume. Specifically, the unique variance in total and regional WMH volumes accounted for by white matter microstructure, brain iron concentration and cerebral blood flow (CBF) was assessed. Regional volumes explored were periventricular and deep regions. Eighty healthy older adults (ages 60–86) were scanned at 3 Tesla MRI using fluid-attenuated inversion recovery, diffusion tensor imaging (DTI), …

The Detrimental Association Between Fear Of Falling And Motor Performance In Older Cancer Patients With Chemotherapy-Induced Peripheral Neuropathy, Gu Eon Kang, Tamiko K Murphy, Mark E Kunik, Hoda J Badr, Biruh T Workeneh, Sarvari V Yellapragada, Yvonne H Sada, Bijan Najafi

Faculty, Staff and Students Publications

BACKGROUND: Cancer patients with chemotherapy-induced peripheral neuropathy (CIPN) are at increased risk of falls and developing fear of falling (FoF). Although FoF may continue to impair motor performance and increase the risk of falling even further, this association remains unexplored in CIPN.

RESEARCH QUESTION: Does high FoF in patients with CIPN further deteriorate motor performance beyond the impairment from CIPN-related sensory deficits?

METHODS: In this secondary analysis of data collected from two clinical trials, gait parameters during habitual walking condition and postural sway parameters during 30-second quiet standing (eye-open and eyes-closed) were compared among older participants (≥ 65 years) with …

Analysis Of Genetic Variants Associated With Levels Of Immune Modulating Proteins For Impact On Alzheimer’S Disease Risk Reveal A Potential Role For Siglec14, Benjamin C. Shaw, Yuriko Katsumata, James F. Simpson, David W. Fardo, Steven Estus

Biostatistics Faculty Publications

Genome-wide association studies (GWAS) have identified immune-related genes as risk factors for Alzheimer’s disease (AD), including TREM2 and CD33, frequently passing a stringent false-discovery rate. These genes either encode or signal through immunomodulatory tyrosine-phosphorylated inhibitory motifs (ITIMs) or activation motifs (ITAMs) and govern processes critical to AD pathology, such as inflammation and amyloid phagocytosis. To investigate whether additional ITIM and ITAM-containing family members may contribute to AD risk and be overlooked due to the stringent multiple testing in GWAS, we combined protein quantitative trait loci (pQTL) data from a recent plasma proteomics study with AD associations in a recent …

Emergency Department - Community Partnership To Coordinate Older Adults Falls Prevention Programs, Suzanne Ryer, Ann Gallo, Adam Perry, Michael Malone

Journal of Geriatric Emergency Medicine

Abstract

Falls and injurious falls are common causes for emergency department visits in older adults. Prior literature describing ED care of older adults has focused on the patients' injuries and their ED care. There is a gap in the literature describing community- based falls prevention strategies and interventions deployed by community organizations, beyond health systems. We identified variation in approaches to older adults among paramedic programs from one community to the next within Milwaukee County, Wisconsin. We also noted no organized falls prevention program spanning all communities, emergency departments and health systems in the county. We describe the implementation of …

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 …

Dysregulation Of Systemic Immunity In Aging And Dementia, Jenny Lutshumba, Barbara S. Nikolajczyk, Adam D. Bachstetter

Pharmacology and Nutritional Sciences Faculty Publications

Neuroinflammation and the tissue-resident innate immune cells, the microglia, respond and contribute to neurodegenerative pathology. Although microglia have been the focus of work linking neuroinflammation and associated dementias like Alzheimer’s Disease, the inflammatory milieu of brain is a conglomerate of cross-talk amongst microglia, systemic immune cells and soluble mediators like cytokines. Age-related changes in the inflammatory profile at the levels of both the brain and periphery are largely orchestrated by immune system cells. Strong evidence indicates that both innate and adaptive immune cells, the latter including T cells and B cells, contribute to chronic neuroinflammation and thus dementia. Neurodegenerative hallmarks …

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 …