Geriatrics Commons^™

Clinically Relevant Intronic Splicing Enhancer Mutation In Myelin Proteolipid Protein Leads To Progressive Microglia And Astrocyte Activation In White And Gray Matter Regions Of The Brain, Adam D. Bachstetter, Scott J. Webster, Linda J. Van Eldik, Franca Cambi

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: Mutations in proteolipid protein (PLP), the most abundant myelin protein in the CNS, cause the X-linked dysmyelinating leukodystrophies, Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2 (SPG2). Point mutations, deletion, and duplication of the PLP1 gene cause PMD/SPG2 with varying clinical presentation. Deletion of an intronic splicing enhancer (ISEdel) within intron 3 of the PLP1 gene is associated with a mild form of PMD. Clinical and preclinical studies have indicated that mutations in myelin proteins, including PLP, can induce neuroinflammation, but the temporal and spatial onset of the reactive glia response in a clinically relevant mild form of PMD …

Circulating Micrornas In Alzheimer's Disease: The Search For Novel Biomarkers, Véronique Dorval, Peter T. Nelson, Sébastien S. Hébert

Sanders-Brown Center on Aging Faculty Publications

Alzheimer's disease (AD) is the most common neurodegenerative disease in the elderly. While advancements have been made in understanding the genetic and molecular basis of AD, the clinical diagnosis of AD remains difficult, and post-mortem confirmation is often required. Furthermore, the onset of neurodegeneration precedes clinical symptoms by approximately a decade. Consequently, there is a crucial need for an early and accurate diagnosis of AD, which can potentially lead to strategies that can slow down or stop the progression of neurodegeneration and dementia. Recent advances in the non-coding RNA field have shown that microRNAs (miRNAs) can function as powerful biomarkers …

Dose- And Time-Dependent Neuroprotective Effects Of Pycnogenol® Following Traumatic Brain Injury, Mubeen A. Ansari, Kelly N. Roberts, Stephen W. Scheff

Sanders-Brown Center on Aging Faculty Publications

After traumatic brain injury (TBI), both primary and secondary injury cascades are initiated, leading to neuronal death and cognitive dysfunction. We have previously shown that the combinational bioflavonoid, Pycnogenol® (PYC), alters some secondary injury cascades and protects synaptic proteins when administered immediately following trauma. The purpose of the present study was to explore further the beneficial effects of PYC and to test whether it can be used in a more clinically relevant fashion. Young adult male Sprague-Dawley rats were subjected to a unilateral moderate/severe cortical contusion. Subjects received a single intravenous (i.v.) injection of PYC (1, 5, or 10 mg/kg) …

Development Of Novel In Vivo Chemical Probes To Address Cns Protein Kinase Involvement In Synaptic Dysfunction, D Martin Watterson, Valerie L. Grum-Tokars, Saktimayee M. Roy, James P. Schavocky, Brinda Desai Bradaric, Adam D. Bachstetter, Bin Xing, Edgardo Dimayuga, Faisal Saeed, Hong Zhang, Agnieszka Staniszewski, Jeffrey C. Pelletier, George Minasov, Wayne F. Anderson, Ottavio Arancio, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Serine-threonine protein kinases are critical to CNS function, yet there is a dearth of highly selective, CNS-active kinase inhibitors for in vivo investigations. Further, prevailing assumptions raise concerns about whether single kinase inhibitors can show in vivo efficacy for CNS pathologies, and debates over viable approaches to the development of safe and efficacious kinase inhibitors are unsettled. It is critical, therefore, that these scientific challenges be addressed in order to test hypotheses about protein kinases in neuropathology progression and the potential for in vivo modulation of their catalytic activity. Identification of molecular targets whose in vivo modulation can attenuate synaptic …

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

Sanders-Brown Center on Aging Faculty Publications

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

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

Sanders-Brown Center on Aging Faculty Publications

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

Are Informal Carers And Community Care Workers Effective In Managing Malnutrition In The Older Adult Community? A Systematic Review Of Current Evidence, Skye Marshall, Judith Bauer, Sandra Capra, Elisabeth Isenring

Skye Marshall

Governing Occupation Through Constructions Of Risk: The Case Of The Aging Driver, Silke Dennhardt

Electronic Thesis and Dissertation Repository

Risk and risk-management have become increasingly pervasive features of modern society and governmentality scholars have highlighted various ways risk discourses are taken up to govern citizens and their everyday conduct. Thus, attending to risk is imperative to advance an understanding of how everyday occupation is shaped and governed within contemporary society. Within this study, the example of driving in later life is drawn upon to address two objectives: 1. to advance the understanding of how risk is taken up to govern everyday occupation, and 2. to explicate how risk is taken up in discourses to constitute particular subjectivities and their …

Planning For The Growing Older Population: Conducting Community Needs Assessments, Caitlin Coyle, Hayley Gravette, Jan Mutchler, Gerontology Institute, University Of Massachusetts Boston

Office of Community Partnerships Posters

Goals and Objectives: To describe the aging population of each community; To investigate the needs, interests and opinions of mature residents relating to their aging needs for age-related services in their respective communities; To provide recommendations to community partners and their stakeholders about how to create strong communities for older adults, based on needs assessment results; Generate reports and other documents to be used by the Department of Elder Services, other town offices, organizations that provide services, advocates, and community members.

Healthy Aging In Massachusetts: Reporting Indicators, Identifying Resources & Activating Allies, Elizabeth Dugan, Frank Porell, Nina Silverstein, Ruth Palombo, Chae Man Lee, Kristina Turk

Office of Community Partnerships Posters

In Massachusetts, a Healthy Aging Collaborative comprised of a diverse group of stakeholders has been formed for multiple purposes: information sharing around healthy aging, idea generation, partnership building and activity mapping.

Intracranial Injection Of Aav Expressing Nep But Not Ide Reduces Amyloid Pathology In App+Ps1 Transgenic Mice, Nikisha Carty, Kevin R. Nash, Milene Brownlow, Dana Cruite, Donna M. Wilcock, Maj-Linda B. Selenica, Daniel C. Lee, Marcia N. Gordon, Dave Morgan

Sanders-Brown Center on Aging Faculty Publications

The accumulation of β-amyloid peptides in the brain has been recognized as an essential factor in Alzheimer's disease pathology. Several proteases, including Neprilysin (NEP), endothelin converting enzyme (ECE), and insulin degrading enzyme (IDE), have been shown to cleave β-amyloid peptides (Aβ). We have previously reported reductions in amyloid in APP+PS1 mice with increased expression of ECE. In this study we compared the vector-induced increased expression of NEP and IDE. We used recombinant adeno-associated viral vectors expressing either native forms of NEP (NEP-n) or IDE (IDE-n), or engineered secreted forms of NEP (NEP-s) or IDE (IDE-s). In a six-week study, immunohistochemistry …

Bapineuzumab Alters Aβ Composition: Implications For The Amyloid Cascade Hypothesis And Anti-Amyloid Immunotherapy, Alex E. Roher, David H. Cribbs, Ronald C. Kim, Chera L. Maarouf, Charisse M. Whiteside, Tyler A. Kokjohn, Ian D. Daugs, Elizabeth Head, Carolyn Liebsack, Geidy Serrano, Christine Belden, Marwan N. Sabbagh, Thomas G. Beach

Sanders-Brown Center on Aging Faculty Publications

The characteristic neuropathological changes associated with Alzheimer's disease (AD) and other lines of evidence support the amyloid cascade hypothesis. Viewing amyloid deposits as the prime instigator of dementia has now led to clinical trials of multiple strategies to remove or prevent their formation. We performed neuropathological and biochemical assessments of 3 subjects treated with bapineuzumab infusions. Histological analyses were conducted to quantify amyloid plaque densities, Braak stages and the extent of cerebral amyloid angiopathy (CAA). Amyloid-β (Aβ) species in frontal and temporal lobe samples were quantified by ELISA. Western blots of amyloid-β precursor protein (AβPP) and its C-terminal (CT) fragments …

The Health Consequences And Healthcare-Seeking Strategies For South American Immigrant Careworkers In Genoa, Italy, Patti A. Meyer

Theses and Dissertations--Anthropology

This research on healthcare strategies of home-based, low-wage, immigrant careworkers contributes to the ways medical anthropology, migration studies and social science understand human-economy-family care relationships and health and carework as commodities in today's global economy. It reveals the consequences for workers as they defray the costs of care for the Italian government and contribute to their home economies. This research was conducted in Genoa, Italy, which has the largest percentage of people over the age of 70 in any city of its size in the world and a tradition of sending and receiving immigrant workers. The main question was: Under …

Comparing Clinical Profiles In Alzheimer's Disease And Parkinson's Disease Dementia, Martin R. Farlow, Frederick A. Schmitt, Dag Aarsland, George T. Grossberg, Monique Somogyi, Xiangyi Meng

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Greater understanding of differences in baseline impairment and disease progression in patients with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) may improve the interpretation of drug effects and the design of future studies.

METHODS: This was a retrospective analysis of three randomized, double-blind rivastigmine databases (one in PDD, two in AD). Impairment on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, 10-item Neuropsychiatric Inventory (NPI-10) and the ADCS-Clinical Global Impression of Change (CGIC) was compared [standardized difference (Cohen's d), similar if <0.1].

RESULTS: Patients with AD or PDD had similar levels …

Spillovers Of Veterans Hospice Care: The Economic And Social Impact Of Palliative Care, Maximiliano Mendieta, Bruce D. Mcdonald Iii

Bruce D. McDonald, III

In exchange for military service in the United States, soldiers are promised a benefits package inclusive of health and education after the completion of their service. While the economic effects of the defense-growth relationship are well known, this study takes a unique approach to understanding the relationship between veterans and society by investigating the social and economic spillovers of veterans hospice care. This study shows that as an early adopter of hospice care, the U.S. Department of Veterans Affairs maximized its efficiency through sponsoring innovative research on geriatric care, introducing competition into the health sector, and legitimizing death and dying …