Geriatrics Commons^™

Rapamycin Rescues Vascular, Metabolic And Learning Deficits In Apolipoprotein E4 Transgenic Mice With Pre-Symptomatic Alzheimer’S Disease, Ai-Ling Lin, Jordan B. Jahrling, Wei Zhang, Nicholas Derosa, Vikas Bakshi, Peter Romero, Veronica Galvan, Arlan Richardson

Sanders-Brown Center on Aging Faculty Publications

Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that apolipoprotein E ɛ4 mice treated with rapamycin had restored cerebral blood flow, blood–brain barrier integrity and glucose metabolism, compared …

The Happy Older Latinos Are Active (Hola) Health Promotion And Prevention Study: Study Protocol For A Pilot Randomized Controlled Trial, Daniel E. Jimenez, Charles F. Reynolds, Margarita Alegría, Philip Harvey, Stephen Bartels

Dartmouth Scholarship

Results of previous studies attest to the greater illness burden of common mental disorders (anxiety and depression) in older Latinos and the need for developing preventive interventions that are effective, acceptable, and scalable. Happy Older Latinos are Active (HOLA) is a newly developed intervention that uses a community health worker (CHW) to lead a health promotion program in order to prevent common mental disorders among at-risk older Latinos. This pilot study tests the feasibility and acceptability of delivering HOLA to older, at-risk Latinos.

Methods/Design: HOLA is a multi-component, health promotion intervention funded by the National Institute of Mental Health (NIMH). …

Pharmacists On The Front Lines Of Polypharmacy: The Individualized Medication Assessment And Planning (Imap) Project To Improve Medication Use In Senior Adults With Cancer, Ginah Nightingale Pharmd, Bcop, Laura T. Pizzi Pharmd, Mph, Emily Hajjar Pharmd, Bcps, Bcacp, Cgp, Elizabeth Pigott, Margaret Wang, Shannon Doherty, Kristine Swartz Md, Andrew Chapman Do, Facp

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

Using An Automated Model To Identify Older Patients At Risk For 30-Day Hospital Readmission And 30-Day Mortality, Ariba Khan, Mary L. Hook, Maharaj Singh, Marsha Vollbrecht, Aaron Malsch, Michael L. Malone

Journal of Patient-Centered Research and Reviews

Background: A real-time electronic health record (EHR) predictive model that identifies older patients at risk for readmission and mortality may assist the health care team in improved patient care.

Purpose: This study was performed to generate an automated 30-day readmission and 30-day mortality risk model using data from the EHR in hospitalized older adults.

Methods: This was a retrospective cohort study. Included were patients age 65 years and older admitted to the hospital from July 2012 to December 2013. An automated predictive model was derived from variables collected from the EHR including socioeconomic factors, medical diagnoses and health care utilization. …

An Automated Model Using Electronic Health Record Data To Identify Delirium Among Hospitalized Older Adults: A Pilot Project, Ariba Khan, Maharaj Singh, Hina Singh, Ayesha Maria, Michelle Simpson

Journal of Patient-Centered Research and Reviews

Background: Delirium is a serious change in mental status with adverse outcomes, but remains underrecognized. The electronic health record (EHR) may assist in the identification of delirium.

Purpose: This study was performed to generate an automated delirium identification model using data from the EHR among hospitalized older adults.

Methods: Inpatients 65 years and older were included in this cross-sectional study. The researchers used “confusion assessment method” as the gold standard to identify delirium. Four categories of variables were obtained from the EHR on the day of and the day prior to researcher assessment: 1) hypoactive delirium (any one of the …

Prognostic Indices For Hospitalized Older Adults: A Meta-Analysis And Systematic Review, Ariba Khan, Ayesha Maria, James Hocker, Maharaj Singh, Michelle Simpson

Journal of Patient-Centered Research and Reviews

Background: A prognostication predictive model incorporated into the electronic health record (EHR) may be useful in assisting the health care team in accurately predicting mortality and may be used in appropriately allocating palliative care services.

Purpose: To systematically review and summarize current medical literature regarding the factors predictive of mortality in an inpatient population above 65 years of age.

Methods: Nondisease-specific prognostication indices that predict 1-year mortality in an inpatient population of adults over age 65 were included. We excluded studies that estimated intensive care unit, disease-specific or in-hospital mortality. A MEDLINE, CINAHL, Ovid and Cochrane literature search of English-language …

Delirium Recognition In Hospitalized Older Patients: A Quality Improvement Project, Jodi Punke, Ariba Khan, Michael L. Malone

Journal of Patient-Centered Research and Reviews

Background: We noted a low reported prevalence of delirium (3%) in hospitalized older patients at a community teaching hospital in north central Wisconsin.

Purpose: This was a quality improvement project to report recognition of delirium by nurses before and after an educational intervention.

Methods: This project was performed on one medical unit in our hospital. Quality improvement data was collected at baseline and after the educational intervention. Data collected included observation by a geriatrician attending weekly interdisciplinary rounds to note any mention by nurses of delirium or confusion. The patient’s electronic health record (EHR) was reviewed to note delirium assessment …

Early Shifts Of Brain Metabolism By Caloric Restriction Preserve White Matter Integrity And Long-Term Memory In Aging Mice, Janet Guo, Vikas Bakshi, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

Preservation of brain integrity with age is highly associated with lifespan determination. Caloric restriction (CR) has been shown to increase longevity and healthspan in various species; however, its effects on preserving living brain functions in aging remain largely unexplored. In the study, we used multimodal, non-invasive neuroimaging (PET/MRI/MRS) to determine in vivo brain glucose metabolism, energy metabolites, and white matter structural integrity in young and old mice fed with either control or 40% CR diet. In addition, we determined the animals’ memory and learning ability with behavioral assessments. Blood glucose, blood ketone bodies, and body weight were also measured. We …

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 …

Engaging Older Adults To Build Social Capital, Beverly K. Lunsford, Danielle Janes

Nursing Faculty Publications

Countries are considering the healthcare implications as the proportion of older adults increases, including rising healthcare costs and resources needed as more adults want to "age in place" or continue living in the community. More in home resources and support services will be needed for older adults to continue living independently at homes. Older adults are an incredibly untapped resource with a continuing need to contribute to society and a willingness to help others. Older adults are working longer than ever before, so they have the potential to build their own social capital for meeting the needs of aging colleagues. …

Abcc9/Sur2 In The Brain: Implications For Hippocampal Sclerosis Of Aging And A Potential Therapeutic Target, Peter T. Nelson, Gregory A. Jicha, Wang-Xia Wang, Eseosa T. Ighodaro, Sergey C. Artiushin, Colin G. Nichols, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium (“K _ATP ”) channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The K _ATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is …

Topical Administration Of Psychotropic Medications In Pluronic Lecithin Organogel To Treat Patients With Dementia: A Retrospective Observational Study, Cornelius W. Thomas, Md, Suzanne Holroyd, Md. Chair, Department Of Psychiatry

Marshall Journal of Medicine

OBJECTIVE: Treatment of mood and behavioral symptoms in geriatric patients with advanced dementia may be impeded by poor compliance with oral medications. Pluronic lecithin organogel (PLO) is a compounding substrate that can be used for the topical administration of psychotropic medications.

METHODS: Charts of patients treated with psychotropic medications compounded with PLO cream were reviewed for treatment outcomes. All patients were treated by a nursing home outreach service.

RESULTS: Records from twenty-four patients, mean age 86.8 + 5.9, were reviewed. Common psychiatric symptoms included agitation, aggressive behavior, and depression. Medications most commonly administered as a PLO cream included quetiapine and …

Dynapenic Obesity And The Effect On Long-Term Physical Function And Quality Of Life: Data From The Osteoarthritis Initiative, John A. Batsis, Alicia J. Zbehlik, Dawna Pidgeon, Stephen J. Bartels

Dartmouth Scholarship

Obesity is associated with functional impairment, institutionalization, and increased mortality risk in elders. Dynapenia is defined as reduced muscle strength and is a known independent predictor of adverse events and disability. The synergy between dynapenia and obesity leads to worse outcomes than either independently. We identified the impact of dynapenic obesity in a cohort at risk for and with knee osteoarthritis on function.

Time-Dependent Effects Of Cx3cr1 In A Mouse Model Of Mild Traumatic Brain Injury, Heidi Y. Febinger, Hannah E. Thomasy, Maria N. Pavlova, Kristyn M. Ringgold, Paulien R. Barf, Amrita M. George, Jenna N. Grillo, Adam D. Bachstetter, Jenny A. Garcia, Astrid E. Cardona, Mark R. Opp, Carmelina Gemma

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Neuroinflammation is an important secondary mechanism that is a key mediator of the long-term consequences of neuronal injury that occur in traumatic brain injury (TBI). Microglia are highly plastic cells with dual roles in neuronal injury and recovery. Recent studies suggest that the chemokine fractalkine (CX3CL1, FKN) mediates neural/microglial interactions via its sole receptor CX3CR1. CX3CL1/CX3CR1 signaling modulates microglia activation, and depending upon the type and time of injury, either protects or exacerbates neurological diseases.

METHODS: In this study, mice deficient in CX3CR1 were subjected to mild controlled cortical impact injury (CCI), a model of TBI. We evaluated …

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 …

Albumin Administration In Acute Ischemic Stroke: Safety Analysis Of The Alias Part 2 Multicenter Trial, Michael D. Hill, Renee H. Martin, Yuko Y. Palesch, Claudias S. Moy, Diego Tamariz, Karla J. Ryckborst, Elizabeth B. Jones, David Weisman, L. Creed Pettigrew, Myron D. Ginsberg

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Albumin treatment of ischemic stroke was associated with cardiopulmonary adverse events in previous studies and a low incidence of intracranial hemorrhage. We sought to describe the neurological and cardiopulmonary adverse events in the ALIAS Part 2 Multicenter Trial.

METHODS: Ischemic stroke patients, aged 18-83 and a baseline NIHSS ≥ 6, were randomized to treatment with ALB or saline control within 5 hours of stroke onset. Neurological adverse events included symptomatic intracranial hemorrhage, hemicraniectomy, neurological deterioration and neurological death. Cardiopulmonary adverse events included pulmonary edema/congestive heart failure, acute coronary syndromes, atrial fibrillation, pneumonia and pulmonary thromboembolism.

RESULTS: …

Novel Human Abcc9/Sur2 Brain-Expressed Transcripts And An Eqtl Relevant To Hippocampal Sclerosis Of Aging, Peter T. Nelson, Wang-Xia Wang, Bernard R. Wilfred, Angela Wei, James Dimayuga, Qingwei Huang, Eseosa T. Ighodaro, Sergey C. Artiushin, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

ABCC9 genetic polymorphisms are associated with increased risk for various human diseases including hippocampal sclerosis of aging. The main goals of this study were 1 > to detect the ABCC9 variants and define the specific 3′ untranslated region (3′UTR) for each variant in human brain, and 2 > to determine whether a polymorphism (rs704180) associated with risk for hippocampal sclerosis of aging pathology is also associated with variation in ABCC9 transcript expression and/or splicing. Rapid amplification of ABCC9 cDNA ends (3′RACE) provided evidence of novel 3′ UTR portions of ABCC9 in human brain. In silico and experimental studies were performed focusing on …

Insights Into Alzheimer’S Disease: The Levels Of Signaling Proteins In Brain Of Control Subjects Versus Brain From Subjects With Mild Cognitive Impairment, Georgianne F. Tiu

Kaleidoscope

The purpose of this study was to measure the expression levels of key signaling proteins in brain tissue from subjects with mild cognitive impairment (MCI) compared to control subjects. MCI is considered to be the beginning phase of Alzheimer’s disease (AD). Tumor necrosis factor alpha (TNF-α), nuclear factor kappa beta (NF-κβ), phospho Bad (pBad), and ubiquitin C-terminal hydrolase-L1 (UCH-L1) are four of the proteins that were investigated. Trends of either decreases or increases in protein expression levels in MCI vs. control brain were investigated. Western blot analysis was used in order to identify these trends. These signaling protein levels are …

Communication Between Family Carers And Health Professionals About End-Of-Life Care For Older People In The Acute Hospital Setting: A Qualitative Study, Glenys Caswell, Kristian Pollock, Rowan Harwood, Davina Porock

Publications and Research

Background: This paper focuses on communication between hospital staff and family carers of patients dying on acute hospital wards, with an emphasis on the family carers’ perspective. The age at which people in the UK die is increasing and many continue to die in the acute hospital setting. Concerns have been expressed about poor quality end of life care in hospitals, in particular regarding communication between staff and relatives. This research aimed to understand the factors and processes which affect the quality of care provided to frail older people who are dying in hospital and their family carers.

Methods: The …

Reversal Of Aging-Related Neuronal Ca2+ Dysregulation And Cognitive Impairment By Delivery Of A Transgene Encoding Fk506-Binding Protein 12.6/1b To The Hippocampus, John C. Gant, Kuey-Chu Chen, Inga Kadish, Eric M. Blalock, Olivier Thibault, Nada M. Porter, Philip W. Landfield

Pharmacology and Nutritional Sciences Faculty Publications

Brain Ca(2+) regulatory processes are altered during aging, disrupting neuronal, and cognitive functions. In hippocampal pyramidal neurons, the Ca(2+)-dependent slow afterhyperpolarization (sAHP) exhibits an increase with aging, which correlates with memory impairment. The increased sAHP results from elevated L-type Ca(2+) channel activity and ryanodine receptor (RyR)-mediated Ca(2+) release, but underlying molecular mechanisms are poorly understood. Previously, we found that expression of the gene encoding FK506-binding protein 12.6/1b (FKBP1b), a small immunophilin that stabilizes RyR-mediated Ca(2+) release in cardiomyocytes, declines in hippocampus of aged rats and Alzheimer's disease subjects. Additionally, knockdown/disruption of hippocampal FKBP1b in young rats augments neuronal Ca(2+) responses. …

Altered Lysosomal Proteins In Neural-Derived Plasma Exosomes In Preclinical Alzheimer Disease, Edward J. Goetzl, Adam Boxer, Janice B. Schwartz, Erin L. Abner, Ronald C. Petersen, Bruce L. Miller, Dimitrios Kapogiannis

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVE: Diverse autolysosomal proteins were quantified in neurally derived blood exosomes from patients with Alzheimer disease (AD) and controls to investigate disordered neuronal autophagy.

METHODS: Blood exosomes obtained once from patients with AD (n = 26) or frontotemporal dementia (n = 16), other patients with AD (n = 20) both when cognitively normal and 1 to 10 years later when diagnosed, and case controls were enriched for neural sources by anti-human L1CAM antibody immunoabsorption. Extracted exosomal proteins were quantified by ELISAs and normalized with the CD81 exosomal marker.

RESULTS: Mean exosomal levels of cathepsin D, lysosome-associated membrane …

Performance-Based Tools For Assessing Functional Performance In Individuals With Mild Cognitive Impairment, Patricia Da Cunha Belchior, Melanie Holmes, Nathalie Bier, Carolina Bottari, Barbara Mazer, Alexandra Robert, Navaldeep Kaur

The Open Journal of Occupational Therapy

Background: It is now recognized that individuals with mild cognitive impairment (MCI) face subtle functional declines that can compromise performance in everyday tasks. However, it is still not clear how to capture these declines in the clinical setting. Thus, the goal of this study was to conduct a scoping review to identify performance-based tools for which the psychometric properties have been evaluated with the MCI population.

Methods: A scoping review of the scientific literature was performed with the guidance of a health science librarian in searching the MEDLINE, PsychINFO, CINAHL, and EMBASE databases from their inception until May 2014.

Results: …

Role Of Mitochondria In Regulating Microrna Activity And Its Relevance To The Central Nervous System, Wang-Xia Wang, Joe E. Springer

Physical Medicine and Rehabilitation Faculty Publications

No abstract provided.

Is The Geriatric Impact Ipad Test A Valid Measurement Of Cognitive Function In Older Adults?, Heather Elise O'Dell

Graduate Theses and Dissertations

The number of older adults will rapidly increase within the next generation (Brookmeyer, Johnson, Ziegler-Graham, & Arrighi, 2007). Alzheimer’s disease risk increases with age, especially after age 60 (NIA, n.d.). Aging leads to a decrease in functional independence, and this side effect is exacerbated by cognitive decline (Johnson, Lui, & Yaffe, 2007). Executive function is a predictor of Alzheimer’s disease onset and progression (Zhang, Han, Verhaeghen, & Nilsson, 2007). The Geriatric ImPACTTM test is a potential new and more convenient testing methods than traditional methods used. The purpose of this research is to validate the Geriatric ImPACTTM test by comparing …

Low Neural Exosomal Levels Of Cellular Survival Factors In Alzheimer's Disease, Edward J. Goetzl, Adam Boxer, Janice B. Schwartz, Erin Abner, Ronald C. Petersen, Bruce L. Miller, Olga D. Carlson, Maja Mustapic, Dimitrios Kapogiannis

Sanders-Brown Center on Aging Faculty Publications

Transcription factors that mediate neuronal defenses against diverse stresses were quantified in plasma neural-derived exosomes of Alzheimer's disease or frontotemporal dementia patients and matched controls. Exosomal levels of low-density lipoprotein receptor-related protein 6, heat-shock factor-1, and repressor element 1-silencing transcription factor all were significantly lower in Alzheimer's disease patients than controls (P < 0.0001). In frontotemporal dementia, the only significant difference was higher levels of repressor element 1-silencing transcription factor than in controls. Exosomal transcription factors were diminished 2-10 years before clinical diagnosis of Alzheimer's disease. Low exosomal levels of survival proteins may explain decreased neuronal resistance to Alzheimer's disease neurotoxic proteins.

Staying Sharp: The Cutting Edge Of Research On Cognition And Aging, Regula H. Robnett

Occupational Therapy Faculty Presentations

Workshop PowerPoint presentation given June 11, 2015, for the 25th Maine Geriatrics Conference in Bar Harbor, Maine. Presentation reviews the latest evidence on cognition and aging. While there is an overwhelming amount of data out there, it is crucial to be informed consumers so the information can be used to enhance one's own life and the lives of others. As people age, changes occur in the brain that can impact learning, memory, and overall daily performance. However, techniques based on promoting preserved skills, embracing new learning, and providing contextual adaptations can be used to improve overall performance. Workshop presentation included …

Apoε2 And Education In Cognitively Normal Older Subjects With High Levels Of Ad Pathology At Autopsy: Findings From The Nun Study, Diego Iacono, Peter Zandi, Myron Gross, William R. Markesbery, Olga Pletnikova, Gay Rudow, Juan C. Troncoso

Sanders-Brown Center on Aging Faculty Publications

Asymptomatic Alzheimer's disease (ASYMAD) subjects are individuals characterized by preserved cognition before death despite substantial AD pathology at autopsy. ASYMAD subjects show comparable levels of AD pathology, i.e. β-amyloid neuritic plaques (Aβ-NP) and tau-neurofibrillary tangles (NFT), to those observed in mild cognitive impairment (MCI) and some definite AD cases. Previous clinicopathologic studies on ASYMAD subjects have shown specific phenomena of hypertrophy in the cell bodies, nuclei, and nucleoli of hippocampal pyramidal neurons and other cerebral areas. Since it is well established that the allele APOε4 is a major genetic risk factor for AD, we examined whether specific alleles of APOE …

Calcium Channel Blockers, Progression To Dementia, And Effects On Amyloid Beta Peptide Production, Mark A. Lovell, Erin Abner, Richard Kryscio, Liou Xu, Shuling X. Fister, Bert C. Lynn

Sanders-Brown Center on Aging Faculty Publications

Previous epidemiologic studies suggest that antihypertensive drugs may be protective against cognitive decline. To determine if subjects enrolled in the University of Kentucky longitudinal aging study who used antihypertensive drugs showed diminished progression to dementia, we used a 3-parameter logistic regression model to compare the rate of progression to dementia for subjects who used any of the five common categories of antihypertensive drugs to those with similar demographic characteristics but who did not use antihypertensives. Regression modeling showed that subjects who used calcium channel blockers (CCBs) but not the other classes of antihypertensives showed a significant decrease in the rate …

Implementation Of An Evidence-Based Educational Workshop And Toolkit: Menopausal Women's Healthcare Needs For The Primary Care Provider, Pamela Doerr-Kashani Dnp, Rn

Doctor of Nursing Practice (DNP) Projects

This evidence-based change of practice project involved the development of an educational workshop for primary care providers (PCPs). The intent of the project was to improve PCP’s knowledge of menopausal health, and to create their comfort level when discussing menopausal healthcare with clients. The workshop Menopausal Women’s Healthcare Needs for the Primary Care Provider (Doerr-Kashani, 2014) was created in response to an identified gap in knowledge among PCPs nationally on menopause-related health issues. The workshop was designed as a resource to support PCPs to competently address women’s menopause-related health issues, and enable them to provide comprehensive, evidence-based care within the …

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 …