Geriatrics Commons^™

Neuroangiogenesis: A Vascular Basis For Alzheimer's Disease And Cognitive Decline During Aging, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Angiogenesis directs development of the brain's microcirculation during antenatal and postnatal development, but its role later in life is less well recognized. I contend that during senescence a reduced cerebral capillary density accounts in part for the vascular cognitive impairment observed in many older persons and possibly for some forms of Alzheimer's disease. I propose that neuroangiogenesis is essential throughout adult life for maintaining the microcirculation of the cerebral cortex and elsewhere in the brain and that it commonly declines with old age. To support this hypothesis I have examined the neurological literature for relevant studies on cerebral capillary density …

Vitamin D Mitigates Age-Related Cognitive Decline Through The Modulation Of Pro-Inflammatory State And Decrease In Amyloid Burden, Teresita L. Briones, Hala Darwish

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Increasing evidence shows an association between the use of vitamin D and improvement in age-related cognitive decline. In this study, we investigated the possible mechanisms involved in the neuroprotective effects of vitamin D on age-related brain changes and cognitive function.

Methods

Male F344 rats aged 20 months (old) and 6 months (young) were used and randomly assigned to either vitamin D supplementation or no supplementation (control). A total of n = 39 rats were used in the study. Rats were individually housed and the supplementation group received a subcutaneous injection of vitamin D (1, α25-dihydroxyvitamin D3) 42 I.U./Kg …

Humor-Related Social Exchanges And Mental Health In Assisted Living Residents, Ann Elizabeth Mcqueen

Dissertations and Theses

Social contact is known to be vital for older adults' mental and physical health, but few studies of social interactions have taken place in long-term care settings. The current study investigated whether the psychological well-being of assisted living residents was influenced by factors associated with residents' social interactions involving humor. Specific aims of the present study were to develop and test a measure related to humor-related social exchanges, to examine how humor-related social exchanges affect residents' mental health, and to explore whether humor-related social exchanges mediated the effects of resident and facility characteristics on indices of mental health. One hundred …

Mild Cognitive Impairment: Statistical Models Of Transition Using Longitudinal Clinical Data, Erin L. Abner, Richard J. Kryscio, Gregory E. Cooper, David W. Fardo, Gregory A. Jicha, Marta S. Mendiondo, Peter T. Nelson, Charles D. Smith, Linda J. Van Eldik, Lijie Wan, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

Mild cognitive impairment (MCI) refers to the clinical state between normal cognition and probable Alzheimer's disease (AD), but persons diagnosed with MCI may progress to non-AD forms of dementia, remain MCI until death, or recover to normal cognition. Risk factors for these various clinical changes, which we term "transitions," may provide targets for therapeutic interventions. Therefore, it is useful to develop new approaches to assess risk factors for these transitions. Markov models have been used to investigate the transient nature of MCI represented by amnestic single-domain and mixed MCI states, where mixed MCI comprised all other MCI subtypes based on …

Will The Use Of Fiber Be As Effective As Laxatives In Relieving Constipation In The Geriatric Population?, Saunders Batunkyi

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not the use of fiber can be as effective as laxatives in relieving constipation in the geriatric population.

STUDY DESIGN: Review of three journals published in English in peer-reviewed journals.

DATA SOURCES: Two randomized controlled trials and one parallel interventional trial investigating the effectiveness of supplemental dietary fiber in managing constipation in elderly populations that are presently reliant on prescription laxatives.

OUTCOMES (S) MEASURED: The outcomes were measured by the frequency of defecation, ease of bowel movement, patient discomfort, patient well being, and undesired effects …

Cost Effectiveness Of A Home-Based Intervention That Helps Functionally Vulnerable Older Adults Age In Place At Home., Eric Jutkowitz, Laura N Gitlin, Laura T. Pizzi, Edward Lee, Marie P Dennis

College of Population Health Faculty Papers

Evaluating cost effectiveness of interventions for aging in place is essential for adoption in service settings. We present the cost effectiveness of Advancing Better Living for Elders (ABLE), previously shown in a randomized trial to reduce functional difficulties and mortality in 319 community-dwelling elders. ABLE involved occupational and physical therapy sessions and home modifications to address client-identified functional difficulties, performance goals, and home safety. Incremental cost-effectiveness ratio (ICER), expressed as additional cost to bring about one additional year of life, was calculated. Two models were then developed to account for potential cost differences in implementing ABLE. Probabilistic sensitivity analyses were …

Microglial P38Α Mapk Is Critical For Lps-Induced Neuron Degeneration, Through A Mechanism Involving Tnfα, Bin Xing, Adam D. Bachstetter, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: The p38α MAPK isoform is a well-established therapeutic target in peripheral inflammatory diseases, but the importance of this kinase in pathological microglial activation and detrimental inflammation in CNS disorders is less well understood. To test the role of the p38α MAPK isoform in microglia-dependent neuron damage, we used primary microglia from wild-type (WT) or p38α MAPK conditional knockout (KO) mice in co-culture with WT cortical neurons, and measured neuron damage after LPS insult.

RESULTS: We found that neurons in co-culture with p38α-deficient microglia were protected against LPS-induced synaptic loss, neurite degeneration, and neuronal death. The involvement of the proinflammatory …

Leaving Home Care: Decision Making, Risk Scenarios & Services Gaps In The Home Care System, Jacey J. Vaughan, Nina M. Silverstein

Gerontology Institute Publications

Home and community-based services (HCBS) enable older and disabled adults to age-in-place in their homes and communities by helping them function independently for as long as possible (Grabowski et al., 2010; Wong & Silverstein, 2011). Previous studies well document that older adults prefer receiving HCBS rather than institutional care at a nursing home (e.g., Walker, 2010; Fox-Grage, Coleman, & Freiman, 2006). Medicaid is a major source of funding for long-term care. Currently, a large proportion of Medicaid funds in most states has been spent on institutional care (National Conference of State Legislatures & AARP, 2009), and older adults and their …

The Role Of Home Environments In Residential Adjustment Decision Making In Later Life, Kimberly Joy Stoeckel

Graduate Doctoral Dissertations

Using the nationally representative Health and Retirement Study, this research explored the multi-faceted influence of the accessibility of housing environments on the occurrence and characteristics of residential adjustments made by older adults aged 70 or older. A range of housing adjustment outcomes were examined, including home modifications and relocation into age-segregated senior housing. Analysis of the accessibility gains following relocation was also included in the empirical analyses.

The Ecological Theory of Aging (Lawton & Nahemow, 1973) provided the conceptual framework for the research. The longitudinal design of the HRS empirically advanced understanding of the key theoretical constructs by sensitizing the …

Elevated Stearoyl-Coa Desaturase In Brains Of Patients With Alzheimer's Disease, Giuseppe Astarita, Kwang-Mook Jung, Vitaly Vasilevko, Nicholas V. Dipatrizio, Sarah K. Martin, David H. Cribbs, Elizabeth Head, Carl W. Cotman, Daniele Piomelli

Sanders-Brown Center on Aging Faculty Publications

The molecular bases of Alzheimer's disease (AD) remain unclear. We used a lipidomic approach to identify lipid abnormalities in the brains of subjects with AD (N = 37) compared to age-matched controls (N = 17). The analyses revealed statistically detectable elevations in levels of non-esterified monounsaturated fatty acids (MUFAs) and mead acid (20:3n-9) in mid-frontal cortex, temporal cortex and hippocampus of AD patients. Further studies showed that brain mRNAs encoding for isoforms of the rate-limiting enzyme in MUFAs biosynthesis, stearoyl-CoA desaturase (SCD-1, SCD-5a and SCD-5b), were elevated in subjects with AD. The monounsaturated/saturated fatty acid ratio ('desaturation index')--displayed a strong …

Use Of The Term "Elderly", Dale Avers, Marybeth Brown, Kevin Chui, Rita A. Wong, Michelle M. Lusardi

All PTHMS Faculty Publications

Using the term elderly for a person who is robust and independent as well as for a person who is frail and dependent says little about the individual.

Rna Oxidation Adducts 8-Ohg And 8-Oha Change With Aβ42 Levels In Late-Stage Alzheimer's Disease, Adam M. Weidner, Melissa A. Bradley, Tina L. Beckett, Dana M. Niedowicz, Amy L.S. Dowling, Sergey V. Matveev, Harry Levine, Mark A. Lovell, M. Paul Murphy

Sanders-Brown Center on Aging Faculty Publications

While research supports amyloid-β (Aβ) as the etiologic agent of Alzheimer's disease (AD), the mechanism of action remains unclear. Evidence indicates that adducts of RNA caused by oxidation also represent an early phenomenon in AD. It is currently unknown what type of influence these two observations have on each other, if any. We quantified five RNA adducts by gas chromatography/mass spectroscopy across five brain regions from AD cases and age-matched controls. We then used a reductive directed analysis to compare the RNA adducts to common indices of AD neuropathology and various pools of Aβ. Using data from four disease-affected brain …

Activation Of Matrix Metalloproteinases Following Anti-Aβ Immunotherapy; Implications For Microhemorrhage Occurrence, Donna M. Wilcock, Dave Morgan, Marcia N. Gordon, Tiffany L. Taylor, Lisa A. Ridnour, David A. Wink, Carol A. Colton

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Anti-Aβ immunotherapy is a promising approach to the prevention and treatment of Alzheimer's disease (AD) currently in clinical trials. There is extensive evidence, both in mice and humans that a significant adverse event is the occurrence of microhemorrhages. Also, vasogenic edema was reported in phase 2 of a passive immunization clinical trial. In order to overcome these vascular adverse effects it is critical that we understand the mechanism(s) by which they occur.

METHODS: We have examined the matrix metalloproteinase (MMP) protein degradation system in two previously published anti-Aβ immunotherapy studies. The first was a passive immunization study in which …

Senior Transportation Abstracts: A Focus On Options, Helen Kerschner, Nina M. Silverstein

Gerontology Institute Publications

This collection of abstracts represents a publication of importance for understanding the needs, challenges, solutions, and/or every day issues related to senior transportation services. While several of the abstracts include information about senior driver safety, the collection’s primary purpose is to present a holistic approach to transportation options for older adults. Such a collection is timely because, although the practice of providing transportation to older adults is not new, research and preparation of practical informational and technical materials related to older adult transportation service needs and service delivery are quite recent.

Elderly Patients And Their Health In Pakistan: Current Status, Issues, Challenges And Opportunities, Waris Qidwai, Tabinda Ashfaq

Department of Family Medicine

No abstract provided.

Massachusetts Senior Legal Assistance Project Needs Evaluation: Current Demand For Legal Services, Alison Gottlieb, Lauren A. Martin, Ellen A. Bruce

Gerontology Institute Publications

The Gerontology Institute at the University of Massachusetts Boston was contracted to conduct a statewide needs assessment for the MSLAP. As agreed upon by the MSLAP Advisory Board, the focus of this assessment was to analyze the demand for services Massachusetts legal service providers have experienced recently as a means to understanding the legal needs of Massachusetts elders (age 60 and older). A second needs assessment was conducted by the Massachusetts Executive Office of Elder Affairs. That needs assessment surveyed home care workers and other elder agency personnel to gauge their assessment of elders’ legal needs in Massachusetts. Read together, …

Evaluation Of The Global Association Between Cholesterol-Associated Polymorphisms And Alzheimer's Disease Suggests A Role For Rs3846662 And Hmgcr Splicing In Disease Risk, Christopher R. Simmons, Fanggeng Zou, Steven G Younkin, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Recent genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNP)s that are essentially unequivocally associated with peripheral cholesterol. Since the alleles of the APOE gene, which modulate peripheral cholesterol metabolism, and midlife plasma cholesterol are both associated with Alzheimer's disease (AD) risk, we have evaluated the hypothesis that SNPs associated with plasma cholesterol are also associated with AD.

RESULTS: Seventeen non-APOE SNPs reproducibly associated with cholesterol per GWAS were tested for association with AD in ~2,000 AD and ~4,000 non-AD subjects. As a group, these SNPs are associated with AD. Two SNPs in particular, rs3846662 and rs1532085, are …

Epigenetic Silencing Of Nucleolar Rrna Genes In Alzheimer's Disease, Maciej Pietrzak, Grzegorz Rempala, Peter T. Nelson, Jing-Juan Zheng, Michal Hetman

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Ribosomal deficits are documented in mild cognitive impairment (MCI), which often represents an early stage Alzheimer's disease (AD), as well as in advanced AD. The nucleolar rRNA genes (rDNA), transcription of which is critical for ribosomal biogenesis, are regulated by epigenetic silencing including promoter CpG methylation.

METHODOLOGY/PRINCIPAL FINDINGS: To assess whether CpG methylation of the rDNA promoter was dysregulated across the AD spectrum, we analyzed brain samples from 10 MCI-, 23 AD-, and, 24 age-matched control individuals using bisulfite mapping. The rDNA promoter became hypermethylated in cerebro-cortical samples from MCI and AD groups. In parietal cortex, the rDNA promoter …

Microglial P38Α Mapk Is A Key Regulator Of Proinflammatory Cytokine Up-Regulation Induced By Toll-Like Receptor (Tlr) Ligands Or Beta-Amyloid (Aβ), Adam D. Bachstetter, Bin Xing, Lucia De Almeida, Edgardo R. Dimayuga, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Overproduction of proinflammatory cytokines from activated microglia has been implicated as an important contributor to pathophysiology progression in both acute and chronic neurodegenerative diseases. Therefore, it is critical to elucidate intracellular signaling pathways that are significant contributors to cytokine overproduction in microglia exposed to specific stressors, especially pathways amenable to drug interventions. The serine/threonine protein kinase p38α MAPK is a key enzyme in the parallel and convergent intracellular signaling pathways involved in stressor-induced production of IL-1β and TNFα in peripheral tissues, and is a drug development target for peripheral inflammatory diseases. However, much less is known about the quantitative …

Analyzing The Impact Of 23 Mg/Day Donepezil On Language Dysfunction In Moderate To Severe Alzheimer's Disease, Steven H. Ferris, Frederick A. Schmitt, Judith Saxton, Sharon Richardson, Joan Mackell, Yijun Sun, Yikang Xu

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: Progressive language impairment is among the primary components of cognitive decline in Alzheimer's disease (AD). Because expressive and receptive language help to maintain emotional connections to caregivers and support the management of AD patients' functional needs, language plays a critical role in patients' emotional and physical health. Using data from a large prospective clinical trial comparing two doses of donepezil in patients with moderate to severe AD, we performed a post hoc analysis to determine whether a higher dose of donepezil was associated with greater benefits in language function.

METHODS: In the original randomized, double-blind clinical trial, 1,467 patients …

Successful Aging And The Epidemiology Of Hiv, David E. Vance, Teena Mcguinness, Karen Musgrove, Nancy Ann Orel, Pariya L. Fazeli

Gerontology Faculty Publications

By 2015, it is estimated that nearly half of those living with HIV in the US will be 50 years of age and older. This dramatic change in the demographics of this clinical population represents unique challenges for patients, health care providers, and society-at-large. Fortunately, because of highly active antiretroviral therapy (HAART) and healthy lifestyle choices, it is now possible for many infected with HIV to age successfully with this disease; however, this depends upon one’s definition of successful aging. It is proposed that successful aging is composed of eight factors: length of life, biological health, cognitive efficiency, mental health, …

Chronic Disease Self-Management Programs: Relevance For Persons With Dementia, Nina M. Silverstein, Alison S. Gottlieb

Gerontology Institute Publications

The context for this study is the work of the Healthy Brain Initiative. The CDC has established a cooperative agreement with the Alzheimer’s Association to develop and implement a multifaceted approach to look at cognitive health as a public health issue. Late in 2010, the Association commissioned a review of the major chronic disease prevention programs from a systems approach to begin to understand the source of findings that Medicare beneficiaries with Alzheimer’s and related disorders are much higher cost than those simply with a single chronic disease and no AD. This led to the conclusion that Chronic Disease Self‐Management …

Ct Scanning Is Sufficient To Clear The Cervical Spine Of Elderly Falls Less Than 5 Feet., Douglas Lehman Md, Rovinder S. Sandhu Md, Leslie Baga Bsn, Farheen Hussain Ms, John J. Hong Md

Administration & Leadership

No abstract provided.

Rheumatoid Arthritis-Associated Polymorphisms Are Not Protective Against Alzheimer's Disease, Christopher R. Simmons, Fanggeng Zou, Steven G Younkin, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Rheumatoid arthritis (RA) and Alzheimer's disease (AD) are inversely associated. To test the hypothesis that genetic elements associated with increased RA risk are associated with decreased AD risk, we evaluated RA genetic risk factors recently identified in genome-wide association studies (GWAS) for their association with AD in a two-stage, case-control analysis.

RESULTS: In our Stage 1 analysis of ~800 AD and ~1,200 non-AD individuals, three of seventeen RA-associated SNPs were nominally associated with AD (p < 0.05) with one SNP, rs2837960, retaining significance after correction for multiple testing (p = 0.03). The rs2837960_G (minor) allele, which is associated with increased RA risk, was associated with increased AD risk. Analysis of these three SNPs in a Stage 2 population, consisting of ~1,100 AD and ~2,600 non-AD individuals, did not confirm their association with AD. Analysis of Stage 1 and 2 combined suggested that rs2837960 shows a trend for association with AD. When the Stage 2 population was age-matched for the Stage 1 population, rs2837960 exhibited a non-significant trend with AD. Combined analysis of Stage 1 and the age-matched Stage 2 subset showed a significant association of rs2837960 with AD (p = 0.002, OR 1.24) that retained significance following correction for age, sex and APOE (p = 0.02, OR = 1.20). Rs2837960 is near BACE2, which encodes an aspartic protease capable of processing the AD-associated amyloid precursor protein. Testing for an association between rs2837960 and the expression of BACE2 isoforms in human brain, we observed a trend between rs2837960 and the total expression of BACE2 and the expression of a BACE2 transcript lacking exon 7 (p = 0.07 and 0.10, respectively).

CONCLUSIONS: RA-associated SNPs are generally not associated with AD. Moreover, rs2837960_G is associated with increased risk of both RA and, in individuals less than …

Evaluation Of A Medical And Mental Health Unit Compared With Standard Care For Older People Whose Emergency Admission To An Acute General Hospital Is Complicated By Concurrent ‘Confusion’: A Controlled Clinical Trial. Acronym: Team: Trial Of An Elderly Acute Care Medical And Mental Health Unit, Rowan H. Harwood, Sarah E. Goldberg, Kathy H. Whittamore, Catherine Russell, John Rf Gladman, Rob G. Jones, Davina Porock, Sarah A. Lewis, Lucy E. Bradshaw, Rachel A. Elliot

Publications and Research

Background: Patients with delirium and dementia admitted to general hospitals have poor outcomes, and their carers report poor experiences. We developed an acute geriatric medical ward into a specialist Medical and Mental Health Unit over an eighteen month period. Additional specialist mental health staff were employed, other staff were trained in the ‘person-centred’ dementia care approach, a programme of meaningful activity was devised, the environment adapted to the needs of people with cognitive impairment, and attention given to communication with family carers. We hypothesise that patients managed on this ward will have better outcomes than those receiving standard care, and …

Standing In The Gap: The Primary Care Physician And Alzheimer’S Disease, Shirley M. Neitch

Internal Medicine

There is a huge volume of information recently published about Alzheimer’s disease, but most of it is not targeted to the average busy primary care physician, even though these PCPs are providing the bulk of care to patients with dementia. This paper is a succinct clinical review of the current state of diagnosis and treatment of Alzheimer’s disease, including citations of resources for physicians and caregivers.

Driving Assessment Results In Patients With A Diagnosis Of Dementia, Shirley M. Neitch, Guillermo Madero, Shawn Maynard

Internal Medicine

Primary care physicians are frequently involved in cases in which they must decide if a patient with dementia should stop driving. The decision is complex, and there are no firm clinical guidelines available. We examined the results of a number of patients who have undergone assessment in our Driving Assessment Clinic, to determine if any of our findings correlated with the diagnosis of dementia. If any associations exist, recommendations may be possible to assist PCPs in making the decision to have patients stop driving, even if full formal testing cannot be done.

Are Scores On The Ppt Useful In Determination Of Risk Of Future Falls In Individuals With Dementia?, Mary K. Farrell, Richard A. Rutt, Michelle M. Lusardi, Ann K. Williams

All PTHMS Faculty Publications

Individuals with dementia or Alzheimer’s disease (AD), exhibit both a progressive decline in cognitive function and accumulating difficulty with physical function.¹ As cognitive impairment begins, individuals will initially demonstrate difficulties with short-term memory and with instrumental activities of daily living. As the dementia progresses, individuals will increasingly demonstrate difficulties with long-term memory, communication, and basic activities of daily living.

Dimensions Of Aging And Belonging For The Older Person And The Effects Of Ageism, Laurence C. Nolan

Brigham Young University Journal of Public Law

No abstract provided.

Patterns Of Microrna Expression In Normal And Early Alzheimer's Disease Human Temporal Cortex: White Matter Versus Gray Matter, Wang-Xia Wang, Qingwei Huang, Yanling Hu, Arnold J. Stromberg, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

MicroRNA (miRNA) expression was assessed in human cerebral cortical gray matter (GM) and white matter (WM) in order to provide the first insights into the difference between GM and WM miRNA repertoires across a range of Alzheimer's disease (AD) pathology. RNA was isolated separately from GM and WM portions of superior and middle temporal cerebral cortex (N = 10 elderly females, postmortem interval < 4 h). miRNA profiling experiments were performed using state-of-the-art Exiqon^© LNA-microarrays. A subset of miRNAs that appeared to be strongly expressed according to the microarrays did not appear to be conventional miRNAs according to Northern blot analyses. Some well-characterized miRNAs were substantially enriched in WM …