Geriatrics Commons^™

Sugihara Causality Analysis Of Scalp Eeg For Detection Of Early Alzheimer's Disease, Joseph C. Mcbride, Xiaopeng Zhao, Nancy B. Munro, Greg A. Jicha, Frederick A. Schmitt, Richard J. Kryscio, Charles D. Smith, Yang Jiang

Sanders-Brown Center on Aging Faculty Publications

Recently, Sugihara proposed an innovative causality concept, which, in contrast to statistical predictability in Granger sense, characterizes underlying deterministic causation of the system. This work exploits Sugihara causality analysis to develop novel EEG biomarkers for discriminating normal aging from mild cognitive impairment (MCI) and early Alzheimer's disease (AD). The hypothesis of this work is that scalp EEG based causality measurements have different distributions for different cognitive groups and hence the causality measurements can be used to distinguish between NC, MCI, and AD participants. The current results are based on 30-channel resting EEG records from 48 age-matched participants (mean age 75.7 …

Effects Of Video Enhancement In A Stated-Choice Experiment On Medical Decision Making, Susanne Hoffmann, Joachim Winter, Francis G. Caro, Alison Gottlieb

Gerontology Institute Publications

Background. The internet can be useful in administering stated-choice experiments to understand medical decision making and refine the content of patient decision aids. In internet-based stated-choice experiments, video and audio files can be used to provide information to respondents. Quality of data may or may not be affected.

Objectives. In a methodological experiment concerned with administration of a stated-choice experiment on the internet concerned with knee-replacement surgery, we compared the data quality obtained with video-enhanced and conventional text formats.

Methods. Members of the RAND Corporation’s American Life Panel and 50 years of age or older (n=1616) were randomly assigned to …

Alzheimer's Therapeutics Targeting Amyloid Beta 1-42 Oligomers I: Abeta 42 Oligomer Binding To Specific Neuronal Receptors Is Displaced By Drug Candidates That Improve Cognitive Deficits, Nicholas J. Izzo, Agnes Staniszewski, Lillian To, Mauro Fa, Andrew F. Teich, Faisal Saeed, Harrison Wostein, Thomas Walko Iii, Anisha Vaswani, Meghan Wardius, Zanobia Syed, Jessica Ravenscroft, Kelsie Mozzoni, Colleen Silky, Courtney Rehak, Raymond Yurko, Patricia Finn, Gary Look, Gilbert Rishton, Hank Safferstein, Miles Miller, Conrad Johanson, Edward Stopa, Manfred Windisch, Birgit Hutter-Paier, Mehrdad Shamloo, Ottavio Arancio, Harry Levine Iii, Susan M. Catalano

Sanders-Brown Center on Aging Faculty Publications

Synaptic dysfunction and loss caused by age-dependent accumulation of synaptotoxic beta amyloid (Abeta) 1-42 oligomers is proposed to underlie cognitive decline in Alzheimer's disease (AD). Alterations in membrane trafficking induced by Abeta oligomers mediates reduction in neuronal surface receptor expression that is the basis for inhibition of electrophysiological measures of synaptic plasticity and thus learning and memory. We have utilized phenotypic screens in mature, in vitro cultures of rat brain cells to identify small molecules which block or prevent the binding and effects of Abeta oligomers. Synthetic Abeta oligomers bind saturably to a single site on neuronal synapses and induce …

Alzheimer's Therapeutics Targeting Amyloid Beta 1–42 Oligomers Ii: Sigma-2/Pgrmc1 Receptors Mediate Abeta 42 Oligomer Binding And Synaptotoxicity, Nicholas J. Izzo, Jinbin Xu, Chenbo Zeng, Molly J. Kirk, Kelsie Mozzoni, Colleen Silky, Courtney Rehak, Raymond Yurko, Gary Look, Gilbert Rishton, Hank Safferstein, Carlos Cruchaga, Alison Goate, Michael A. Cahill, Ottavio Arancio, Robert H. Mach, Rolf Craven, Elizabeth Head, Harry Levine Iii, Tara L. Spires-Jones, Susan M. Catalano

Sanders-Brown Center on Aging Faculty Publications

Amyloid beta (Abeta) 1-42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer's disease (AD). We have identified a receptor not previously associated with AD that mediates the binding of Abeta oligomers to neurons, and describe novel therapeutic antagonists of this receptor capable of blocking Abeta toxic …

Which Clinical Guidelines Should Be Implemented For Management Of Osteopenia In Primary Care? A Clin-Iq, Turia Hollingsworth

Journal of Patient-Centered Research and Reviews

Literature review was conducted to determine clinical guidelines for osteopenia management of immunocompetent patients in the primary care setting. It was concluded that pharmacological treatment should be offered to patients with osteopenia if they are considered high risk, which can be determined by utilizing the World Health Organization Fracture Risk Assessment Tool (FRAX^®) to evaluate 10-year risk. Patients with a calculated hip fracture probability of at least 3% or those with probability of 20% or more for all osteoporotic fractures may be offered bisphosphonate therapy.

The P38alpha Mitogen-Activated Protein Kinase Limits The Cns Proinflammatory Cytokine Response To Systemic Lipopolysaccharide, Potentially Through An Il-10 Dependent Mechanism, Adam D. Bachstetter, Bin Xing, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: The p38α mitogen-activated protein kinase (MAPK) is a well-characterized intracellular kinase involved in the overproduction of proinflammatory cytokines from glia. As such, p38α appears to be a promising therapeutic target for neurodegenerative diseases associated with neuroinflammation. However, the in vivo role of p38α in cytokine production in the CNS is poorly defined, and prior work suggests that p38α may be affecting a yet to be identified negative feedback mechanism that limits the acute, injury-induced proinflammatory cytokine surge in the CNS.

METHODS: To attempt to define this negative feedback mechanism, we used two in vitro and two in vivo models …

Self-Reported Memory Complaints: Implications From A Longitudinal Cohort With Autopsies, Richard J. Kryscio, Erin L. Abner, Gregory E. Cooper, David W. Fardo, Greg A. Jicha, Peter T. Nelson, Charles D. Smith, Linda J. Van Eldik, Lijie Wan, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVE: We assessed salience of subjective memory complaints (SMCs) by older individuals as a predictor of subsequent cognitive impairment while accounting for risk factors and eventual neuropathologies.

METHODS: Subjects (n = 531) enrolled while cognitively intact at the University of Kentucky were asked annually if they perceived changes in memory since their last visit. A multistate model estimated when transition to impairment occurred while adjusting for intervening death. Risk factors affecting the timing and probability of an impairment were identified. The association between SMCs and Alzheimer-type neuropathology was assessed from autopsies (n = 243).

RESULTS: SMCs were …

Interpersonal Communication In The Context Of Dementia: Examining Family Caregivers' Appraisals And Burden, Stacy Lynn Barnes

Dissertations (1934 -)

Purpose and Objectives: The purpose of this study was to explore dementia family caregivers' appraisals of communication behaviors and strategies, and their relationships to caregiver burden. Study objectives were to investigate: 1) the relationship between frequency of dementia-related communication behaviors and caregivers' appraisals of frustration; 2) the relationship between caregivers' use of communication strategies and appraisals of helpfulness; 3) the structural relationships between communication behavior appraisal, communication strategy appraisal, problem behaviors, and caregiver burden; and 4) caregiver education level as a moderating variable of the final structural model. Methods: A written, mailed questionnaire was developed to capture dementia family caregivers' …

Con: Are We Ready To Translate Alzheimer's Disease-Modifying Therapies To People With Down Syndrome?, Elizabeth Head, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Adults with Down syndrome develop Alzheimer's disease neuropathology in an age-dependent manner. This unique feature provides an opportunity to test interventions targeted for prevention of Alzheimer's disease neuropathology and dementia in Down syndrome.

DISCUSSION: In considering clinical trial designs, however, there are several challenges that we believe will be critical to examine further. These include: accuracy in dementia, mild cognitive impairment and preclinical Alzheimer's disease diagnoses in Down syndrome; clinical trial outcome measures appropriate for individuals with Down syndrome; in vivo imaging outcome measures (and practical considerations); and contributions of medical co-morbidities to disease progression. Also, when studies are …

Calcineurin And Glial Signaling: Neuroinflammation And Beyond, Jennifer L. Furman, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Similar to peripheral immune/inflammatory cells, neuroglial cells appear to rely on calcineurin (CN) signaling pathways to regulate cytokine production and cellular activation. Several studies suggest that harmful immune/inflammatory responses may be the most impactful consequence of aberrant CN activity in glial cells. However, newly identified roles for CN in glutamate uptake, gap junction regulation, Ca²⁺ dyshomeostasis, and amyloid production suggest that CN's influence in glia may extend well beyond neuroinflammation. The following review will discuss the various actions of CN in glial cells, with particular emphasis on astrocytes, and consider the implications for neurologic dysfunction arising with aging, injury, …

Generation And Behavior Characterization Of Camkiiβ Knockout Mice, Adam D. Bachstetter, Scott J. Webster, Tao Tu, Danielle S. Goulding, Jacques Haiech, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

The calcium/calmodulin-dependent protein kinase II (CaMKII) is abundant in the brain, where it makes important contributions to synaptic organization and homeostasis, including playing an essential role in synaptic plasticity and memory. Four genes encode isoforms of CaMKII (α, β, δ, γ), with CaMKIIα and CaMKIIβ highly expressed in the brain. Decades of molecular and cellular research, as well as the use of a large number of CaMKIIα mutant mouse lines, have provided insight into the pivotal roles of CaMKIIα in brain plasticity and cognition. However, less is known about the CaMKIIβ isoform. We report the development and extensive behavioral and …

The Impact Of Waist Circumference On Function And Physical Activity In Older Adults: Longitudinal Observational Data From The Osteoarthritis Initiative, John A. Batsis, Alicia J. Zbehlik, Laura K. Barre, Todd A. Mackenzie, Stephen J. Bartels

Dartmouth Scholarship

Background: We previously demonstrated that BMI is associated with functional decline and reduced quality of life. While BMI in older adults is fraught with challenges, waist circumference (WC) is a marker of visceral adiposity that can also predict mortality. However, its association with function and quality of life in older adults is not well understood and hence we sought to examine the impact of WC on six-year outcomes.

Methods: We identified adults aged ≥60 years from the longitudinal Osteoarthritis Initiative and stratified the cohort into quartiles based on WC. Our primary outcome measures of function at six year follow-up included: …

Identification Of Functional Parameters For The Classification Of Older Female Fallers And Prediction Of ‘First-Time’ Fallers, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

Falls remain a challenge for ageing societies. Strong evidence indicates that a previous fall is the strongest single screening indicator for a subsequent fall and the need for assessing fall risk without accounting for fall history is therefore imperative. Testing in three functional domains (using a total 92 measures) were completed in 84 older women (60–85 years of age), including muscular control, standing balance, and mean and variability of gait. Participants were retrospectively classified as fallers (n = 38) or non-fallers (n = 42) and additionally in a prospective manner to identify first-time fallers (FTFs) (n = 6) within a …

Transition From An M1 To A Mixed Neuroinflammatory Phenotype Increases Amyloid Deposition In App/Ps1 Transgenic Mice, Erica M. Weekman, Tiffany L. Sudduth, Erin L. Abner, Gabriel J. Popa, Michael D. Mendenhall, Holly M. Brothers, Kaitlyn Braun, Abigail Greenstein, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: The polarization to different neuroinflammatory phenotypes has been described in early Alzheimer's disease, yet the impact of these phenotypes on amyloid-beta (Aβ) pathology remains unknown. Short-term studies show that induction of an M1 neuroinflammatory phenotype reduces Aβ, but long-term studies have not been performed that track the neuroinflammatory phenotype.

METHODS: Wild-type and APP/PS1 transgenic mice aged 3 to 4 months received a bilateral intracranial injection of adeno-associated viral (AAV) vectors expressing IFNγ or green fluorescent protein in the frontal cortex and hippocampus. Mice were sacrificed 4 or 6 months post-injection. ELISA measurements were used for IFNγ protein levels and …

Low Zinc Levels Is Associated With Increased Inflammatory Activity But Not With Atherosclerosis, Arteriosclerosis Or Endothelial Dysfunction Among The Very Elderly, Ehimen Aneni, Khurram Nasir

All Publications

BACKGROUND:

Reduced zinc intake has been related to atherogenesis and arteriosclerosis. We verified this assumption in very old individuals, which are particularly prone to both zinc deficiency and structural and functional changes in the arterial wall.

METHODS:

Subjects (n = 201, 80-102 years) with uneventful cardiovascular history and who were not in use of anti-inflammatory treatments in the last 30-days were enrolled. Daily intake of zinc, lipid profile, plasma C-reactive protein (CRP), plasma zinc, flow-mediated dilation (FMD), carotid ultrasonography and cardiac computed tomography were obtained. Young's Elastic Modulus, Stiffness Index and Artery Compliance were calculated.

RESULTS:

There was no significant …

Quantitative Ultrasound: Measurement Considerations For The Assessment Of Muscular Dystrophy And Sarcopenia, Michael O. Harris-Love, Reza Monfaredi, Catheeja Ismail, Marc R. Blackman, Kevin Cleary

Exercise and Nutrition Sciences Faculty Publications

Diagnostic musculoskeletal ultrasound has potential clinical utility in characterizing pathological muscle tissue. Sonography has been long proposed as method of assessing muscle damage due to neuromuscular diseases such as muscular dystrophy, and more recently, changes in body and tissue composition associated with muscle wasting disorders such as sarcopenia. The use of quantitative ultrasound as an adjunct diagnostic procedure has different technical challenges than the traditional use of ultrasound in clinical medicine. Operator-dependent technique and variation are critical considerations when obtaining measures of echointensity (i.e., tissue composition estimates) and tissue dimensions (i.e., muscle thickness) – key elements of the ultrasound assessment …

Frontal White Matter Integrity In Adults With Down Syndrome With And Without Dementia, David K. Powell, Allison Caban-Holt, Greg A. Jicha, William C. Robertson, Roberta Davis, Brian T. Gold, Frederick A. Schmitt, Elizabeth Head

Magnetic Resonance Imaging and Spectroscopy Center Faculty Publications

Adults with Down syndrome (DS) are at high risk for developing Alzheimer's disease after the age of 40 years. To detect white matter (WM) changes in the brain linked to dementia, fractional anisotropy (FA) from diffusion tensor imaging was used. We hypothesized that adults with DS without dementia (DS n = 10), DS with dementia (DSAD n = 10) and age matched non-DS subjects (CTL n = 10) would show differential levels of FA and an association with scores from the Brief Praxis Test and the Severe Impairment Battery. WM integrity differences in DS compared with CTL were found predominantly …

Obesity And Diabetes Cause Cognitive Dysfunction In The Absence Of Accelerated Β-Amyloid Deposition In A Novel Murine Model Of Mixed Or Vascular Dementia, Dana M. Niedowicz, Valerie L. Reeves, Thomas L. Platt, Katharina Kohler, Tina L. Beckett, David K. Powell, Tiffany L. Lee, Travis R. Sexton, Eun Suk Song, Lawrence D. Brewer, Caitlin S. Latimer, Susan D. Kraner, Kara L. Larson, Sabire Özcan, Christopher M. Norris, Louis B. Hersh, Nada M. Porter, Donna M. Wilcock, Michael Paul Murphy

Sanders-Brown Center on Aging Faculty Publications

Mid-life obesity and type 2 diabetes mellitus (T2DM) confer a modest, increased risk for Alzheimer's disease (AD), though the underlying mechanisms are unknown. We have created a novel mouse model that recapitulates features of T2DM and AD by crossing morbidly obese and diabetic db/db mice with APP^ΔNL/ΔNLx PS1^P264L/P264L knock-in mice. These mice (db/AD) retain many features of the parental lines (e.g. extreme obesity, diabetes, and parenchymal deposition of β-amyloid (Aβ)). The combination of the two diseases led to additional pathologies-perhaps most striking of which was the presence of severe cerebrovascular pathology, including aneurysms and small …

Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio

Sanders-Brown Center on Aging Faculty Publications

Aims: To evaluate the relationship between self-reported head injury and cognitive impairment, dementia, mortality, and Alzheimer's disease (AD)-type pathological changes. Methods: Clinical and neuropathological data from participants enrolled in a longitudinal study of aging and cognition (n = 649) were analyzed to assess the chronic effects of self-reported head injury. Results: The effect of self-reported head injury on the clinical state depended on the age at assessment: for a 1-year increase in age, the OR for the transition to clinical mild cognitive impairment (MCI) at the next visit for participants with a history of head injury was 1.21 and 1.34 …

Humor's Effect On Short-Term Memory In Older Adults: An Innovative Wellness Paradigm, Gurinder Singh Bains

Loma Linda University Electronic Theses, Dissertations & Projects

Context: With ageing, the detrimental effects of stress can impair the ability to learn and sustain memory. Humor and the associated mirthful laughter can reduce stress by decreasing the hormone cortisol. Chronic release of cortisol can damage hippocampal neurons leading to impairment of learning and memory. Objectives: To examine the effect of watching a humor video on short term memory in older adults. Design: A randomized, controlled trial. Setting: Loma Linda University, Loma Linda, CA. Participants: 30 subjects: 20 normal healthy, older adults, 11 males and 9 females; 10 Type 2 Diabetic older adults, 6 males and 4 females. Intervention: …

Personality And Functional Vision In Older Adults With Age-Related Macular Degeneration, Barry W. Rovner, R. J. Casten, Mark T. Hegel, Robert W. Massof, Benjamin E. Leiby, Allen C. Ho, William S. Tasman

Department of Psychiatry and Human Behavior Faculty Papers

Introduction: The purpose of the study was to determine whether personality traits influence self-reported functional vision in patients with age-related macular degeneration (AMD). Methods: This is a prospective cross-sectional analysis of baseline data from the Low Vision Depression Prevention Trial. Participants (N = 182) over age 65 with bilateral AMD, visual acuity worse than 20/70 in the better-seeing eye, and subthreshold depression were recruited from the Wills Eye Hospital retina practice. Assessments included visual acuity, contrast sensitivity, National Eye Institute Visual Function Questionnaire-25 plus Supplement (NEI VFQ-25) near and distance subscales, depression, and personality testing. Structural equation models were used …

Predictors Of Hospitalization Among Newly Admitted Skilled Nursing Facility Residents: Rethinking The Role Of Functional Decline, Sun J. Kim, Joo H. Lee, Shunichi Nakagawa, Elizabeth Bukowy, Ankoor Biswas, Boram Han, Yeilim Cho, Hyun Phil Shin, Ji Won Yoo

Journal of Patient-Centered Research and Reviews

Purpose: Hospital transfer from a skilled nursing facility (SNF) is costly, and many are potentially preventable. This study examines: 1) whether functional decline is a predictor of hospital transfer, and 2) the magnitude of relationships between predictors (functional impairment and chronic medical illness) and hospital transfer from SNFs.

Methods: We used Minimum Data Set (MDS) Version 2.0 in the state of Michigan between 2007 and 2009. In total, 196,662 new SNF admissions were observed. Multilevel generalized estimating equations and regression models were performed for each functional and clinical domain while adjusting for demographic variables and change in activities of daily …

Integrated Care For Older Adults In Rural Communities, Eileen Griffin Jd, Andrew F. Coburn Phd

Mental Health / Substance Use Disorders

Recognizing that traditional models of health care delivery and payment often produce fragmented and costly care and poor outcomes for those with the highest needs, many reforms under the Affordable Care Act (ACA) focus on realigning payment incentives and integrating care. These reforms presuppose the existence of supporting infrastructure and capacity, including dedicated care management staffing and health information technology and exchange. With a focus on community-dwelling older adults in need of integrated physical, behavioral health services, and long term services and supports (LTSS), this brief reviews the opportunities and challenges these reform initiatives present for rural communities: How easily …

Habilitation Training Curriculum: Is It Useful?, Ryan K. Cole, Christine Wyman

Thinking Matters Symposium Archive

Alzheimer’s disease is the most common form of dementia, affecting approximately five million Americans. Paul Raia, PhD, Vice President, Clinical Services at the Alzheimer’s Association, MA/NH Chapters, developed a training curriculum called Caring for People with Alzheimer’s Disease: A Habilitation Training Curriculum. The Alzheimer’s Association’s Maine Chapter has been implementing this training in care facilities across Maine. The purpose of this project was to evaluate if this training is perceived as useful in direct care settings.A secondary goal of the project was to determine if this training should be adapted for use in other settings in which professionals of varying …

[Sabbatical Report], Dana Burr Bradley

Sabbatical Reports

Write, submit and present information on geriatrics.

Genetics Of Picalm Expression And Alzheimer's Disease, Ishita Parikh, David W. Fardo, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

Novel Alzheimer's disease (AD) risk factors have been identified by genome-wide association studies. Elucidating the mechanism underlying these factors is critical to the validation process and, by identifying rate-limiting steps in AD risk, may yield novel therapeutic targets. Here, we evaluated the association between the AD-associated polymorphism rs3851179 near PICALM, which encodes a clathrin-coated pit accessory protein. Immunostaining established that PICALM is expressed predominately in microvessels in human brain. Consistent with this finding, PICALM mRNA expression correlated with expression of the endothelial genes vWF and CD31. Additionally, we found that PICALM expression was modestly increased with the rs3851179A …

Elderly Foot Care, Helen Chu

International Conference: Overcoming Challenges in Active Ageing

No abstract provided.

One-And-A-Half Syndrome : An Unusual Cause Of Dizziness, Daniel Haimowitz Md, Facp, Cmd, Catherine M. Glew Bm, Bs, Cmd, Yelena Schpigel Md

Department of Medicine

No abstract provided.

A Program For Review Of Residents On Anti-Psychotic (Ap) Medications In A County Owned Nursing Facility, Catherine M. Glew Bm, Bs, Cmd, Beth Berklite Rn, Adon, Terri Bauer Rn

Department of Medicine

No abstract provided.

Expression Of Mir-15/107 Family Micrornas In Human Tissues And Cultured Rat Brain Cells, Wang-Xia Wang, Robert J. Danaher, Craig S. Miller, Joseph R. Berger, Vega G. Nubia, Bernard R. Wilfred, Janna H. Neltner, Christopher M. Norris, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

The miR-15/107 family comprises a group of 10 paralogous microRNAs (miRNAs), sharing a 5' AGCAGC sequence. These miRNAs have overlapping targets. In order to characterize the expression of miR-15/107 family miRNAs, we employed customized TaqMan Low-Density micro-fluid PCR-array to investigate the expression of miR-15/107 family members, and other selected miRNAs, in 11 human tissues obtained at autopsy including the cerebral cortex, frontal cortex, primary visual cortex, thalamus, heart, lung, liver, kidney, spleen, stomach and skeletal muscle. miR-103, miR-195 and miR-497 were expressed at similar levels across various tissues, whereas miR-107 is enriched in brain samples. We also examined the expression …