Neurology Commons^™

Biomarker And Clinical Trial Design Support For Disease-Modifying Therapies: Report Of A Survey Of The Eu/Us: Alzheimer's Disease Task Force, Jeffrey Cummings, Nick Fox, Bruno Vellas, Paul Aisen, Guogen Shan

Environmental & Global Health Faculty Research

BACKGROUND: Disease-modifying therapies are urgently needed for the treatment of Alzheimer’s disease (AD). The European Union/United States (EU/US) Task Force represents a broad range of stakeholders including biopharma industry personnel, academicians, and regulatory authorities. OBJECTIVES: The EU/US Task Force represents a community of knowledgeable individuals who can inform views of evidence supporting disease modification and the development of disease-modifying therapies (DMTs). We queried their attitudes toward clinical trial design and biomarkers in support of DMTs. DESIGN/SETTING/PARTICIANTS: A survey of members of the EU/US Alzheimer’s Disease Task Force was conducted. Ninety-three members (87%) responded. The details were analyzed to understand what …

Factors Associated With End-Of-Life Planning In Huntington Disease., Nancy R Downing, Siera Goodnight, Sena Chae, Joel S Perlmutter, Michael Mccormack, Elizabeth Hahn, Stacey K Barton, Noelle Carlozzi

Rowan-Virtua School of Osteopathic Medicine Departmental Research

OBJECTIVE: Knowledge of one's gene status for adult onset conditions provides opportunity to make advance end-of-life (EOL) plans. The purposes of these analyses were to (1) determine the prevalence of EOL plans, including advance directives (ADs) among persons across 3 stages of Huntington disease (HD) and (2) examine factors associated with having ADs in this sample.

METHODS: Data are from 503 participants in the HD Quality of Life study. Participants completed an online health-related quality-of-life survey that included questions regarding EOL planning and self-reported HD symptoms. Frequencies were calculated for EOL planning by the HD stage. Bivariate analysis and logistic …

Conserved Brain Myelination Networks Are Altered In Alzheimer's And Other Neurodegenerative Diseases., Mariet Allen, Xue Wang, Jeremy D Burgess, Jens Watzlawik, Daniel J Serie, Curtis S Younkin, Thuy Nguyen, Kimberly G Malphrus, Sarah Lincoln, Minerva M Carrasquillo, Charlotte Ho, Paramita Chakrabarty, Samantha Strickland, Melissa E Murray, Vivek Swarup, Daniel H Geschwind, Nicholas T Seyfried, Eric B Dammer, James J Lah, Allan I Levey, Todd E Golde, Cory Funk, Hongdong Li, Nathan D Price, Ronald C Petersen, Neill R Graff-Radford, Steven G Younkin, Dennis W Dickson, Julia R Crook, Yan W Asmann, Nilüfer Ertekin-Taner

Articles, Abstracts, and Reports

INTRODUCTION: Comparative transcriptome analyses in Alzheimer's disease (AD) and other neurodegenerative proteinopathies can uncover both shared and distinct disease pathways.

METHODS: We analyzed 940 brain transcriptomes including patients with AD, progressive supranuclear palsy (PSP; a primary tauopathy), and control subjects.

RESULTS: We identified transcriptional coexpression networks implicated in myelination, which were lower in PSP temporal cortex (TCX) compared with AD. Some of these associations were retained even after adjustments for brain cell population changes. These TCX myelination network structures were preserved in cerebellum but they were not differentially expressed in cerebellum between AD and PSP. Myelination networks were downregulated in …

Word-List Intrusion Errors Predict Progression To Mild Cognitive Impairment, Kelsey R Thomas, Joel Eppig, Emily C Edmonds, Diane M Jacobs, David J Libon, Rhoda Au, David P Salmon, Mark W Bondi, Alzheimer’S Disease Neuroimaging Initiative

Rowan-Virtua School of Osteopathic Medicine Departmental Research

OBJECTIVE: Preclinical Alzheimer's disease (AD) defined by a positive AD biomarker in the presence of normal cognition is presumed to precede mild cognitive impairment (MCI). Subtle cognitive deficits and cognitive inefficiencies in preclinical AD may be detected through process and error scores on neuropsychological tests in those at risk for progression to MCI.

METHOD: Cognitively normal participants (n = 525) from the Alzheimer's Disease Neuroimaging Initiative were followed for up to 5 years and classified as either stable normal (n = 305) or progressed to MCI (n = 220). Cox regressions were used to determine whether baseline process scores on …

Suicidal Ideation Assessment In Individuals With Premanifest And Manifest Huntington Disease., Melissa Wesson, Nicholas R Boileau, Joel S Perlmutter, Jane S Paulsen, Stacey K Barton, Michael K Mccormack, Noelle E Carlozzi

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Huntington disease (HD) is associated with increased risk of suicide.

OBJECTIVE: This study compares suicide ideation in HD to the general population, assesses factors associated with increased prevalence of suicidal thoughts, and compares clinician-rated to self-reported assessments of suicidal ideation.

METHODS: We examined 496 participants with premanifest or manifest HD. Clinician-rated suicidal ideation was measured using the Problem Behaviors Assessment - short form. Self-reported ideation was measured using two items from the HDQLIFE Concern with Death and Dying item bank. Independent sample t-tests were conducted to compare the prevalence of suicidal thoughts between our HD sample and the U.S. …

Baseline White Matter Hyperintensities And Hippocampal Volume Are Associated With Conversion From Normal Cognition To Mild Cognitive Impairment In The Framingham Offspring Study., Katherine J Bangen, Sarah R Preis, Lisa Delano-Wood, Philip A Wolf, David J Libon, Mark W Bondi, Rhoda Au, Charles Decarli, Adam M Brickman

Rowan-Virtua School of Osteopathic Medicine Departmental Research

INTRODUCTION: We examined associations between magnetic resonance imaging (MRI) markers of cerebrovascular disease and neurodegeneration with mild cognitive impairment (MCI) diagnosis at baseline and conversion from normal cognition to MCI at follow-up.

METHODS: Framingham Offspring participants underwent brain MRI and neuropsychological assessment at baseline (n=1049) and follow-up (n=561). Participants were classified at baseline and at follow-up as cognitively normal or MCI using sensitive neuropsychological criteria. White matter hyperintensity (WMH) volume, covert brain infarcts, hippocampal volume, and total cerebral brain volume were quantified.

RESULTS: Baseline measures of WMH and hippocampal volume were associated with MCI status cross-sectionally and also with conversion …

Assessing Working Memory In Mild Cognitive Impairment With Serial Order Recall., Sheina Emrani, David J Libon, Melissa Lamar, Catherine C Price, Angela L Jefferson, Katherine A Gifford, Timothy J Hohman, Daniel A Nation, Lisa Delano-Wood, Amy Jak, Katherine J Bangen, Mark W Bondi, Adam M Brickman, Jennifer Manly, Rodney Swenson, Rhoda Au, Consortium For Clinical And Epidemiological Neuropsychological Data Analysis (Cenda)

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Working memory (WM) is often assessed with serial order tests such as repeating digits backward. In prior dementia research using the Backward Digit Span Test (BDT), only aggregate test performance was examined.

OBJECTIVE: The current research tallied primacy/recency effects, out-of-sequence transposition errors, perseverations, and omissions to assess WM deficits in patients with mild cognitive impairment (MCI).

METHODS: Memory clinic patients (n = 66) were classified into three groups: single domain amnestic MCI (aMCI), combined mixed domain/dysexecutive MCI (mixed/dys MCI), and non-MCI where patients did not meet criteria for MCI. Serial order/WM ability was assessed by asking participants to repeat …

Intra-Arterial Nitroglycerin As Directed Acute Treatment In Experimental Ischemic Stroke, Michael E. Maniskas, Jill M. Roberts, Rebecca Trueman, Annastazia E. Learoyd, Amanda A. Gorman, Justin F. Fraser, Gregory J. Bix

Neuroscience Faculty Publications

BACKGROUND: Nitroglycerin (also known as glyceryl trinitrate (GTN)), a vasodilator best known for treatment of ischemic heart disease, has also been investigated for its potential therapeutic benefit in ischemic stroke. The completed Efficacy of Nitric Oxide in Stroke trial suggested that GTN has therapeutic benefit with acute (within 6 hours) transdermal systemic sustained release therapy.

OBJECTIVE: To examine an alternative use of GTN as an acute therapy for ischemic stroke following successful recanalization.

METHODS: We administered GTN IA following transient middle cerebral artery occlusion in mice. Because no standard dose of GTN is available following emergent large vessel occlusion, we …

Cognitive Trajectory Changes Over 20 Years Before Dementia Diagnosis: A Large Cohort Study., Ge Li, Eric B Larson, Jane B Shofer, Paul K Crane, Laura E Gibbons, Wayne Mccormick, J D Bowen, Mary Lou Thompson

Articles, Abstracts, and Reports

BACKGROUND/OBJECTIVES: Longitudinal studies have shown an increase in cognitive decline many years before clinical diagnosis of dementia. We sought to estimate changes, relative to "normal" aging, in the trajectory of scores on a global cognitive function test-the Cognitive Abilities Screening Instrument (CASI).

DESIGN: A prospective cohort study.

SETTING: Community-dwelling members of a U.S. health maintenance organization.

PARTICIPANTS: Individuals aged 65 and older who had no dementia diagnosis at baseline and had at least two visits with valid CASI test score (N = 4,315).

MEASUREMENTS: Average longitudinal trajectories, including changes in trajectory before clinical diagnosis in those who would be diagnosed …

Does Music Therapy Intervention Have An Effect On The Emotional Behavior Of Alzheimer Patients?, Alexandra P. Lahurd

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not music therapy intervention have an effect on emotional behavior of Alzheimer patients. Behavior variables measuring are agitation and anxiety.

STUDY DESIGN: Systematic review of two randomized, controlled trials published in 2009 and 2014, respectively, and one randomized control case study published in 2006.

DATA SOURCE: Three published studies comparing music therapy intervention on behavioral modifications with Alzheimer patients were found using PubMed and Medline

OUTCOMES MEASURES: All three studies measure behavior in Alzheimer patients based on a variety of well validated …

Brain Imaging In Older Patients With Delirium, Laila M. Hasan, Ariba Khan, Maharaj Singh, Michael L. Malone

Journal of Patient-Centered Research and Reviews

Background: Delirium is a common, serious and costly condition in older patients admitted to the hospital. This study describes the prevalence and results of brain imaging among a cohort of older hospitalized patients with and without delirium.

Purpose: Investigate the frequency and results of brain imaging in older patients with delirium as compared to those without delirium.

Methods: This was a cross-sectional study. Data were collected on hospitalized patients age 65 years or older who were admitted to 3 hospitals in Milwaukee, Wisconsin, during a 1-month period in the fall of 2013. Subjects were tested for delirium via the “Confusion …

Impact Of Home Visit Capacity On Genetic Association Studies Of Late-Onset Alzheimer's Disease., David W Fardo, Laura E Gibbons, Shubhabrata Mukherjee, M Maria Glymour, Wayne Mccormick, Susan M Mccurry, James D Bowen, Eric B Larson, Paul K Crane

Articles, Abstracts, and Reports

INTRODUCTION: Findings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits.

METHODS: We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators.

RESULTS: …

Pro-Angiogenesis Therapy And Aging: A Mini-Review, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Apart from major illnesses and chronic afflictions, the elderly experience lesser ailments, such as muscle weakness, cold intolerance, and transient memory lapses. Physical signs in the aged include wrinkled skin and the slow healing of skin abrasions. These ailments and signs are grouped together because they may be due in part to an age-linked, waning microcirculation. A reduced capillary density (CD) throughout the body of aged people and animals has been reported in over 40 papers. The reduced CD is due in turn to declining levels of angiogenic growth factors (AGFs) throughout the body during old age, as documented in …

Risk Of Incident Clinical Diagnosis Of Alzheimer's Disease-Type Dementia Attributable To Pathology-Confirmed Vascular Disease, Hiroko H. Dodge, Jian Zhu, Randy Woltjer, Peter T. Nelson, David A. Bennett, Nigel J. Cairns, David W. Fardo, Jeffrey A. Kaye, Deniz-Erten Lyons, Nora Mattek, Julie A. Schneider, Lisa C. Silbert, Chengjie Xiong, Lei Yu, Frederick A. Schmitt, Richard J. Kryscio, Erin L. Abner, Smart Data Consortium

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: The presence of cerebrovascular pathology may increase the risk of clinical diagnosis of Alzheimer's disease (AD).

METHODS: We examined excess risk of incident clinical diagnosis of AD (probable and possible AD) posed by the presence of lacunes and large infarcts beyond AD pathology using data from the Statistical Modeling of Aging and Risk of Transition study, a consortium of longitudinal cohort studies with more than 2000 autopsies. We created six mutually exclusive pathology patterns combining three levels of AD pathology (low, moderate, or high AD pathology) and two levels of vascular pathology (without lacunes and large infarcts or with …

Optimizing Medication Appropriateness In Older Adults: A Randomized Clinical Interventional Trial To Decrease Anticholinergic Burden, Daniela C. Moga, Erin L. Abner, Dorinda N. Rigsby, Lynne Eckmann, Mark Huffmyer, Richard R. Murphy, Beth B. Coy, Gregory A. Jicha

Pharmacy Practice and Science Faculty Publications

Background

The complexity of medication therapy in older adults with multiple comorbidities often leads to inappropriate prescribing. Drugs with anticholinergic properties are of particular interest because many are not recognized for this property; their use may lead to increased anticholinergic burden resulting in significant health risks, as well as negatively impacting cognition. Medication therapy management (MTM) interventions showed promise in addressing inappropriate medication use, but the effectiveness of targeted multidisciplinary team interventions addressing anticholinergic medications in older populations is yet to be determined.

Methods

We conducted an 8-week, parallel-arm, randomized trial to evaluate whether a targeted patient-centered pharmacist–physician team MTM …

Aging And Muscle Fatigability In The Upper Extremity, Andrew Kuplic

Master's Theses (2009 -)

Aging is accompanied by reductions in strength and contraction velocity, and increased fatigability of limb muscles during high-velocity dynamic contractions. These age-related changes affect functional tasks and are well described for the lower limb, with less known about the upper limb muscles. The aims of the thesis were to compare in young and old men and women: (1) maximal torque and power of the elbow flexor muscles across a range of isokinetic velocities, and (2) the neural (supraspinal) and muscular mechanisms of fatigue induced by high-velocity dynamic contractions of the elbow flexor muscles. 28 young (23.2 ± 2.6 years) men …

Amyloid Β–Associated Cognitive Decline In The Absence Of Clinical Disease Progression And Systemic Illness, Karra Harrington, Yen Lim, David Ames, Jason Hassenstab, Simon Laws, Ralph Martins, Stephanie Rainey-Smith, Joanne Robertson, Christopher Rowe, Olivier Salvado, Vincent Dore, Victor Villemagne, Peter Snyder, Colin Masters, Paul Maruff, Aibl Research Group

Research outputs 2014 to 2021

Introduction

High levels of amyloid β (Aβ) are associated with cognitive decline in cognitively normal (CN) older adults. This study investigated the nature of cognitive decline in healthy individuals who did not progress to mild cognitive impairment or dementia.

Method

Cognition was measured over 72 months and compared between low (Aβ−) and high (Aβ+) CN older adults (n = 335) who did not progress to mild cognitive impairment or dementia and who remained free of severe or uncontrolled systemic illness.

Results

Compared to the Aβ− group, the Aβ+ group showed no cognitive impairment at baseline but showed substantial decline …

Self-Reported Sleep Apnea And Dementia Risk: Findings From The Prevention Of Alzheimer's Disease With Vitamin E And Selenium Trial, Xiuhua Ding, Richard J. Kryscio, Joshua Turner, Gregory A. Jicha, Gregory E. Cooper, Allison M. Caban-Holt, Frederick A. Schmitt, Erin L. Abner

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVES: To investigate the association between baseline sleep apnea and risk of incident dementia in the Prevention of Alzheimer's Disease with Vitamin E and Selenium (PREADViSE) study and to explore whether the association depends on apolipoprotein E (APOE) ɛ4 allele status.

DESIGN: Secondary analysis based on data collected during PREADViSE.

SETTING: Participants were assessed at 128 local clinical study sites during the clinical trial phase and later were followed by telephone from a centralized location.

PARTICIPANTS: Men enrolled in PREADViSE (without dementia or other active neurological conditions that affect cognition such as major psychiatric disorders, including depression; N = …

Caloric Restriction Preserves Memory And Reduces Anxiety Of Aging Mice With Early Enhancement Of Neurovascular Functions, Ishita Parikh, Janet Guo, Kai-Hsiang Chuang, Yu Zhong, Ralf G. Rempe, Jared D. Hoffman, Rachel Armstrong, Björn Bauer, Anika M. S. Hartz, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

Neurovascular integrity plays an important role in protecting cognitive and mental health in aging. Lifestyle interventions that sustain neurovascular integrity may thus be critical on preserving brain functions in aging and reducing the risk for age-related neurodegenerative disorders. Here we show that caloric restriction (CR) had an early effect on neurovascular enhancements, and played a critical role in preserving vascular, cognitive and mental health in aging. In particular, we found that CR significantly enhanced cerebral blood flow (CBF) and blood-brain barrier function in young mice at 5-6 months of age. The neurovascular enhancements were associated with reduced mammalian target of …

An Unusual Case Of Escherichia Coli Meningitis And Bacteremia In An Elderly Woman Presenting With Intractable Low Back Pain, Andrea M. Lauffer, Mahmoud Shorman, Carl Mccomas

Marshall Journal of Medicine

Abstract

Introduction:

We report an unusual case of E. coli meningitis in an elderly woman who presented to the emergency room with a chief complaint of intractable low back pain.

Case Description:

A 67 year old woman presented to the emergency room for a chief complaint of intractable low back pain. After admission, the patient developed delirium. Blood cultures were drawn. Patient underwent a lumbar puncture which revealed purulent cerebrospinal fluid. Results of the cerebrospinal fluid and blood cultures revealed pan-sensitive E. coli.

Conclusion:

In the geriatric population, delayed presentation of meningitis can occur for various reasons. With the older …

New Measures To Capture End Of Life Concerns In Huntington Disease: Meaning And Purpose And Concern With Death And Dying From Hdqlife (A Patient-Reported Outcomes Measurement System)., N E Carlozzi, N R Downing, M K Mccormack, S G Schilling, J S Perlmutter, E A Hahn, J S Lai, S Frank, K A Quaid, J S Paulsen, D Cella, S M Goodnight, J A Miner, M A Nance

Rowan-Virtua School of Osteopathic Medicine Departmental Research

PURPOSE: Huntington disease (HD) is an incurable terminal disease. Thus, end of life (EOL) concerns are common in these individuals. A quantitative measure of EOL concerns in HD would enable a better understanding of how these concerns impact health-related quality of life. Therefore, we developed new measures of EOL for use in HD.

METHODS: An EOL item pool of 45 items was field tested in 507 individuals with prodromal or manifest HD. Exploratory and confirmatory factor analyses (EFA and CFA, respectively) were conducted to establish unidimensional item pools. Item response theory (IRT) and differential item functioning analyses were applied to …

Hdqlife: Development And Assessment Of Health-Related Quality Of Life In Huntington Disease (Hd), N E Carlozzi, S G Schilling, J-S Lai, J S Paulsen, E A Hahn, J S Perlmutter, C A Ross, N R Downing, A L Kratz, M K Mccormack, M A Nance, K A Quaid, J C Stout, R C Gershon, R E Ready, J A Miner, S K Barton, S L Perlman, S M Rao, S Frank, I Shoulson, H Marin, M D Geschwind, P Dayalu, S M Goodnight, D Cella

Rowan-Virtua School of Osteopathic Medicine Departmental Research

PURPOSE: Huntington disease (HD) is a chronic, debilitating genetic disease that affects physical, emotional, cognitive, and social health. Existing patient-reported outcomes (PROs) of health-related quality of life (HRQOL) used in HD are neither comprehensive, nor do they adequately account for clinically meaningful changes in function. While new PROs examining HRQOL (i.e., Neuro-QoL-Quality of Life in Neurological Disorders and PROMIS-Patient-Reported Outcomes Measurement Information System) offer solutions to many of these shortcomings, they do not include HD-specific content, nor have they been validated in HD. HDQLIFE addresses this by validating 12 PROMIS/Neuro-QoL domains in individuals with HD and by using established PROMIS …

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 …

1H-Mrs Metabolites In Adults With Down Syndrome: Effects Of Dementia, Ai-Ling Lin, David Powell, Allison Caban-Holt, Gregory A. Jicha, William C. Robertson, Brian T. Gold, Roberta Davis, Erin L. Abner, Donna M. Wilcock, Frederick A. Schmitt, Elizabeth Head

Sanders-Brown Center on Aging Faculty Publications

To determine if proton magnetic resonance spectroscopy (¹H-MRS) detect differences in dementia status in adults with Down syndrome (DS), we used ¹H-MRS to measure neuronal and glial metabolites in the posterior cingulate cortex in 22 adults with DS and in 15 age- and gender-matched healthy controls. We evaluated associations between ¹H-MRS results and cognition among DS participants. Neuronal biomarkers, including N-acetylaspartate (NAA) and glutamate-glutamine complex (Glx), were significantly lower in DS patients with Alzheimer's should probably be changed to Alzheimer (without ' or s) through ms as per the new naming standard disease (DSAD) when …

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.

The Role Of Capillaries In The Lesser Ailments Of Old Age And In Alzheimer's Disease And Vascular Dementia: The Potential Of Pro-Therapeutic Angiogenesis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Apart from chronic diseases (arthritis, diabetes, etc.), old age is generally characterized by three lesser ailments: muscle weakness, minor memory lapses, and cold intolerance. This trio of complaints may have a common, underlying cause, namely, the age-associated reduced microcirculation in muscles, brain, skin, and elsewhere in the body. The Angiogenesis Hypothesis proposes that old age is in part a deficiency disease due to the decline in angiogenic (AG) factors, resulting in a reduced capillary density (CD) throughout the body. Over fifty published papers document waning levels of AG factors and/or decreased CD in various organ systems of aged animals and …

Mice Deficient In Endothelial Α5 Integrin Are Profoundly Resistant To Experimental Ischemic Stroke, Jill Roberts, Leon De Hoog, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

Stroke is a disease in dire need of better therapies. We have previously shown that a fragment of the extracellular matrix proteoglycan, perlecan, has beneficial effects following cerebral ischemia via the α5β1 integrin receptor. We now report that endothelial cell selective α5 integrin deficient mice (α5 KO) are profoundly resistant to ischemic infarct after transient middle cerebral artery occlusion. Specifically, α5 KOs had little to no infarct 2–3 days post-stroke, whereas controls had an increase in mean infarct volume over the same time period as expected. Functional outcome is also improved in the α5 KOs compared with controls. Importantly, no …

Muscle Weakness During Aging: A Deficiency State Involving Declining Angiogenesis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

This essay begins by proposing that muscle weakness of old age from sarcopenia is due in large part to reduced capillary density in the muscles, as documented in 9 reports of aged persons and animals. Capillary density (CD) is determined by local levels of various angiogenic factors, which also decline in muscles with aging, as reported in 7 studies of old persons and animals. There are also numerous reports of reduced CD in the aged brain and other studies showing reduced CD in the kidney and heart of aged animals. Thus a waning angiogenesis throughout the body may be …

Dementia In The Context Of Disability, Rosanne Dizazzo-Miller, Fredrick D. Pociask

Department of Health Care Sciences

Patients and caregivers often associate dementia with devastation and a loss of productive contribution to society. People with dementia are often depicted as confused individuals struggling through embarrassing episodes, followed by a loss of independence. The burden and devastation of the diagnosis on the families of people with dementia is exacerbated by their assumption of the role of caregiver with inadequate preparation or training. Disability scholars, in contrast, offer physical and occupational therapists a nontragic view of disability that recognizes the importance of countering the stigma and discrimination that too often accompany dementia. This case example of a woman diagnosed …

Reporting Practices, Knowledge And Opinion Of Policy Regarding Drivers With Dementia Among Arkansas Neurologists And Geriatricians, Erika Martin Gergerich

Graduate Theses and Dissertations

Background: States have various policies regarding a physician's ability or responsibility to report at-risk drivers with dementia to the Department of Motor Vehicles (DMV). Some states have mandatory reporting policies, others have optional reporting policies and some have no policy regarding this issue. Arkansas has no reporting policy regarding drivers with dementia to the DMV. Therefore, physicians in Arkansas face the risk of liability if they report a patient against their will to the DMV in good faith. Neurologists and geriatricians are often in a position to diagnose and treat individuals with dementia. Research Questions: The following three research questions …