Geriatrics Commons^™

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 …

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 …

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 …

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.

Massachusetts’ Home Care Programs And Reasons For Discharge Into Nursing Homes, Cathy M. Wong, Nina M. Silverstein

Gerontology Institute Publications

Home and community-based services (HCBS) are a range of long-term care services intended to enable older adults and persons with disabilities to “age in place” in their own homes and communities. Previous studies well document that older adults prefer receiving HCBS rather than institutional care at a nursing home. One study concluded that 84 percent of older Americans, aged 50 years and older, want to remain in their homes for as long as possible. 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, …

Cx3cl1 Reduces Neurotoxicity And Microglial Activation In A Rat Model Of Parkinson's Disease, Mibel M. Pabon, Adam D. Bachstetter, Charles E. Hudson, Carmelina Gemma, Paula C. Bickford

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Parkinson's disease is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. The cause of the neurodegeneration is unknown. Neuroinflammation has been clearly shown in Parkinson's disease and may be involved in the progressive nature of the disease. Microglia are capable of producing neuronal damage through the production of bioactive molecules such as cytokines, as well as reactive oxygen species (ROS), and nitric oxide (NO). The inflammatory response in the brain is tightly regulated at multiple levels. One form of immune regulation occurs via neurons. Fractalkine (CX3CL1), produced by neurons, suppresses the activation of microglia. CX3CL1 …

Attention-Deficit/Hyperactivity Disorder In Childhood Is Associated With Cognitive Test Profiles In The Geriatric Population But Not With Mild Cognitive Impairment Or Alzheimer's Disease, N. Ivanchak, Erin L. Abner, S. A. Carr, S. J. Freeman, A. Seybert, John Ranseen, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

The frequency of ADHD in the aging population and its relationship to late-life cognitive decline has not been studied previously. To address this gap in our understanding, the Wender-Utah ADHD Rating scale (WURS) was administered to 310 geriatric subjects with cognitive status ranging from normal cognition to mild cognitive impairment to overt dementia. The frequency of WURS-positive ADHD in this sample was 4.4%. WURS scores were not related to cognitive diagnoses, but did show nonlinear associations with tasks requiring sustained attention. The frequency of ADHD appears stable across generations and does not appear to be associated with MCI or dementia …

Risk Factors For Driving Cessation Vary By Race And Ethnicity, Elizabeth Dugan, Frank Porell, Chae Man Lee

Gerontology Institute Publications

Driving is related to our identity and independence as well as allowing us to get needed goods, services, and social opportunities that enrich daily life. Yet with increasing age, the risk for developing threats to medical fitness to drive increases. Driving cessation is related to a long list of negative outcomes, such as: depression, social isolation, diminished access to health care, and diminished quality of life. We investigated risks for driving cessation, paying close attention to racial differences. This study used data from the Health and Retirement Study (HRS), 1998-2008. The study included N=46, 528 older people (age 65 and …

Conformation Dependent Monoclonal Antibodies Distinguish Different Replicating Strains Or Conformers Of Prefibrillar Aβ Oligomers, Rakez Kayed, Isabel Canto, Leonid Breydo, Suhail Rasool, Tamas Lukacsovich, Jessica Wu, Ricardo Albay, Anna Pensalfini, Stephen Yeung, Elizabeth Head, J. Lawrence Marsh, Charles Glabe

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Age-related neurodegenerative diseases share a number of important pathological features, such as accumulation of misfolded proteins as amyloid oligomers and fibrils. Recent evidence suggests that soluble amyloid oligomers and not the insoluble amyloid fibrils may represent the primary pathological species of protein aggregates.

RESULTS: We have produced several monoclonal antibodies that specifically recognize prefibrillar oligomers and do not recognize amyloid fibrils, monomer or natively folded proteins. Like the polyclonal antisera, the individual monoclonals recognize generic epitopes that do not depend on a specific linear amino acid sequence, but they display distinct preferences for different subsets of prefibrillar oligomers. Immunological …

Deficient Liver Biosynthesis Of Docosahexaenoic Acid Correlates With Cognitive Impairment In Alzheimer's Disease, Giuseppe Astarita, Kwang-Mook Jung, Nicole C. Berchtold, Vinh Q. Nguyen, Daniel L. Gillen, Elizabeth Head, Carl W. Cotman, Daniele Piomelli

Sanders-Brown Center on Aging Faculty Publications

Reduced brain levels of docosahexaenoic acid (C22:6n-3), a neurotrophic and neuroprotective fatty acid, may contribute to cognitive decline in Alzheimer's disease. Here, we investigated whether the liver enzyme system that provides docosahexaenoic acid to the brain is dysfunctional in this disease. Docosahexaenoic acid levels were reduced in temporal cortex, mid-frontal cortex and cerebellum of subjects with Alzheimer's disease, compared to control subjects (P = 0.007). Mini Mental State Examination (MMSE) scores positively correlated with docosahexaenoic/α-linolenic ratios in temporal cortex (P = 0.005) and mid-frontal cortex (P = 0.018), but not cerebellum. Similarly, liver docosahexaenoic acid content was lower in Alzheimer's …

Program Evaluation Of A Community-Based Door-Through-Door Medical Escort Service, Lauren A. Martin

Gerontology Institute Publications

This report summarizes the program evaluation findings of a Boston-based organization’s Medical Escort program. This “door-through-door” service strives to provide medical transportation, physical assistance, and emotional support to elders on their way to the doctor’s office, during medical appointments and on the way back home again. By offering added assistance the program attempts to remove environmental barriers associated with access to health care. This evaluation combines previously collected program statistics with surveys (32) from program volunteers and phone interviews (78) with recipients.

Omega-3 Fatty Acids: Potential Role In The Management Of Early Alzheimer's Disease, Gregory A. Jicha, William R. Markesbery

Sanders-Brown Center on Aging Faculty Publications

Omega-3 fatty acids are essential for brain growth and development. They play an important role throughout life, as critical modulators of neuronal function and regulation of oxidative stress mechanisms, in brain health and disease. Docosahexanoic acid (DHA), the major omega-3 fatty acid found in neurons, has taken on a central role as a target for therapeutic intervention in Alzheimer's disease (AD). A plethora of in vitro, animal model, and human data, gathered over the past decade, highlight the important role DHA may play in the development of a variety of neurological and psychiatric disorders, including AD. Cross sectional and prospective …

Assessing Stakeholder Opinions Of Medical Review Of Impaired Drivers And Fitness To Drive: Recommendations For Massachusetts, Nina M. Silverstein, Kelli Barton

Gerontology Institute Publications

Driving is the main mode of travel for Americans age 65 and older, and although older adults are generally found to be safe drivers, aging often brings about functional limitations and an increase in medications that can impede safe driving and fitness to drive (Rosenbloom, 2003; Kissinger, 2008; Adler & Silverstein, 2008). Effective licensing policies and Medical Advisory Board practices are critical components in identifying medically at-risk drivers and may even have a role in the transition to alternative transportation options; yet, states vary greatly in their approach to licensing and renewal practices and in the utilization, composition, and function …

Using Internet‐Based Vignette Methods To Understand Elder Residential Choices, Francis G. Caro, Teck Ho, Daniel Mcfadden, Alison Gottlieb, Christine Yee, Taizan Chan, Joachim Winter

Gerontology Institute Publications

This paper illustrates an innovative method of administering fractional factorial surveys (vignettes) using the internet. The approach makes it possible to use video clips to deliver information. The method also provides subjects with interactive options before making judgments. A study to determine the views of older people regarding residential options is used to illustrate the method. The study found that the following characteristics of vignette persons affected subject recommendations: personal introduction, functional status, social network, and current housing characteristics. However, characteristics of retirement community features and personal financial status did not affect recommendations.

Focal Cerebral Ischemia In The Tnfalpha-Transgenic Rat, L. Creed Pettigrew, Mark S. Kindy, Stephen W. Scheff, Joe E. Springer, Richard J. Kryscio, Yizhao Li, David S. Grass

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: To determine if chronic elevation of the inflammatory cytokine, tumor necrosis factor-alpha (TNFalpha), will affect infarct volume or cortical perfusion after focal cerebral ischemia.

METHODS: Transgenic (TNFalpha-Tg) rats overexpressing the murine TNFalpha gene in brain were prepared by injection of mouse DNA into rat oocytes. Brain levels of TNFalpha mRNA and protein were measured and compared between TNFalpha-Tg and non-transgenic (non-Tg) littermates. Mean infarct volume was calculated 24 hours or 7 days after one hour of reversible middle cerebral artery occlusion (MCAO). Cortical perfusion was monitored by laser-Doppler flowmetry (LDF) during MCAO. Cortical vascular density was quantified by stereology. …

Living With Alzheimer’S Disease: A Study Of Adult Day Health Services In Massachusetts, Nina M. Silverstein, Cathy M. Wong, Kristen E. Brueck

Gerontology Institute Publications

The role of adult day health care (ADHC) is gaining increased attention as the nation prepares for the large cohort of baby boomers entering their later years. Many boomers are aging with physical and cognitive impairments, including Alzheimer's disease and related dementias. Projections indicate that Massachusetts, along with the nation as a whole, is experiencing an increasing rate of older persons as baby boomers enter late-life. The Commonwealth can expect that persons with Alzheimer's disease and their care partners will need community-based services that are specifically designed for adults with cognitive impairments. However, a report by the Robert Wood Johnson …

Neuropathological Findings Processed By Artificial Neural Networks (Anns) Can Perfectly Distinguish Alzheimer's Patients From Controls In The Nun Study, Enzo Grossi, Massimo P. Buscema, David Snowdon, Piero Antuono

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Many reports have described that there are fewer differences in AD brain neuropathologic lesions between AD patients and control subjects aged 80 years and older, as compared with the considerable differences between younger persons with AD and controls. In fact some investigators have suggested that since neurofibrillary tangles (NFT) can be identified in the brains of non-demented elderly subjects they should be considered as a consequence of the aging process. At present, there are no universally accepted neuropathological criteria which can mathematically differentiate AD from healthy brain in the oldest old. The aim of this study is to discover …

Similar Promotion Of Abeta1-42 Fibrillogenesis By Native Apolipoprotein E Epsilon3 And Epsilon4 Isoforms, David Sweeney, Ralph Martins, Harry Levine, Jonathan D. Smith, Sam Gandy

Sanders-Brown Center on Aging Faculty Publications

The apolipoprotein E epsilon4 allele contributes to the genetic susceptibility underlying a large proportion (~40-60%) of typical, sporadic Alzheimer disease. Apolipoprotein E deficient mice made transgenic for human apolipoprotein E epsilon4 accumulate excess cerebral amyloid when compared to similarly prepared mice expressing human apolipoprotein E epsilon3. Therefore, it is important to search for relevant interactions(s) between apolipoprotein E epsilon4 and Abeta in order to clarify the biological role for apolipoprotein E epsilon4 in Alzheimer disease. Using a thioflavine T (ThT)-based assay, we have investigated the effects of native human apolipoprotein E isoforms on the kinetics of Abeta fibrillogenesis. No obvious …

Consumer Perspectives On Quality In Adult Day Care, Amy Leventhal Stern, Francis G. Caro

Gerontology Institute Publications

Purpose: The purpose of this project was to gain insight into the quality of care and services provided through adult day care from the user’s perspective. Design and Methods: The project utilized 13 focus groups to explore aspects associated with user needs, preferences, and satisfaction with adult day care centers. Results: Focus group participants described aspects of adult day care that are important in delivering quality care, program features that are effective, and key areas in need of improvement. Ensuring the safety of clients; having caring, friendly, and compassionate staff available to provide one-on-one attention; engaging clients in stimulating activities; …

Back To The Future: The Future Of Long-Term Care In Massachusetts, Deborah H. Thomson, John J. Ford

Gerontology Institute Publications

The state of Massachusetts, like the rest of the United States, is facing an approaching crisis in long-term care. Over the next few decades the number of Massachusetts residents age 65 and older will soar. As these numbers increase, so will the need for long-term care.

Massachusetts is ill prepared to provide the services that will be needed. Our current system of health care benefits leaves many elders with gaps in coverage. Those individuals who need long-term services often impoverish themselves and their spouses before the state pays for their care. Others languish on waiting lists to receive services. Our …

Long-Term Care: Informed By Research, Francis G. Caro

Gerontology Institute Publications

Health services research has contributed to health policy and service developments that have led to major improvements in the quality of long-term care in the United States. This policy brief highlights a few areas in which publicly and privately funded research has informed the long-term care field.

Seniors Count Follow-Up Study, Nina M. Silverstein, Heather Connors, May Jawad

Gerontology Institute Publications

Seniors Count is an ongoing outreach initiative under the direction of Boston Mayor Thomas M. Menino with the leadership and support of Joyce Williams, Boston's Commissioner on Affairs of the Elderly. The program's purpose is to "identify and reach out to those members of the city's elderly population who live in private housing arrangements and help provide them with the information and services they [may] need" (Boston Commission on Affairs of the Elderly, 2002). Since the program's inception in 1999, it has reached over 5,500 community-dwelling elders in the City of Boston (Boston Commission on Affairs of the Elderly, 2002). …

Transportation: A Crucial Issue For Adult Day Care In Vermont, Francis G. Caro, Regula H. Robnett, Jennifer Higgins

Gerontology Institute Publications

Transportation arrangements are an integral but fragile element in the effectiveness of adult day care services in Vermont and nationwide. Almost by definition, adult day center participants generally cannot drive due to cognitive and/or physical limitations. Since adult day care services are congregate in nature and serve community-residing elders, this long-term care option is feasible only when there are arrangements to transport elders to and from service centers. Transportation is therefore a major issue for adult day care services.

The aim of this report is to call attention to transportation issues in adult day care services in Vermont. The report …

Working Paper: Elders In Massachusetts Prefer Paid Caregivers, Francis G. Caro

Gerontology Institute Publications

Older Massachusetts residents would rather have paid professionals provide their long-term care than their own children, according to a recent UMass Poll of 461 Massachusetts residents.

Toward Improved Support For Research On Delivery Of Home- And Community-Based Long-Term Care, Francis G. Caro

Gerontology Institute Publications

Stronger and more consistent support is needed for research on long-term care. A greater investment in research will strengthen the ability of public and private organizations to provide effective and efficient assistance to people with disabilities and their informal caregivers. This paper provides a rationale for stronger research funding for the field and outlines several options to strengthen research.

Nursing Home Ownership And Public Policy: An Historical Analysis, K. R. Kaffenberger

Graduate Doctoral Dissertations

In the early days of the United States, care of the disabled elderly outside the home meant the public almshouse. By the 1920s, private, nonprofit homes for the aged were prevalent. More recently, private, for-profit facilities have grown to dominate the field.

For-profit ownership has been controversial. Underlying the controversy is the concern that quality might be lowered in order to enhance profit.

This study asks why most nursing homes are privately owned and why most privately owned nursing homes are operated for profit. It does so with reference to The Nonprofit Economy, in which Burton Weisbrod describes a …

Grandparents Today: A Demographic Profile, Maximiliane E. Szinovacz

Sociology & Criminal Justice Faculty Publications

This article presents a demographic profile of grandparents, using the National Survey of Families and Households. Specific dimensions of grandparenthood addressed include grandparents' survival, the timing of grandparenthood, grandparents' involvement in other roles, surrogate parenting, and stepgrandparents. The data indicate considerable heterogeneity among grandparents of different genders and races or ethnicities. They also suggest modifications in previous descriptions of modern grandparenthood.