Banerjee R.,University of Michigan |
Yung R.,Geriatrics Research
Aging Cell | Year: 2014
Regulatory T-cell (Treg, CD4+CD25+) dysfunction is suspected to play a key role in immune senescence and contributes to increased susceptibility to diseases with age by suppressing T-cell responses. FoxP3 is a master regulator of Treg function, and its expression is under control of several epigenetically labile promoters and enhancers. Demethylation of CpG sites within these regions is associated with increased FoxP3 expression and development of a suppressive phenotype. We examined differences in FoxP3 expression between young (3-4 months) and aged (18-20 months) C57BL/6 mice. DNA from CD4+ T cells is hypomethylated in aged mice, which also exhibit increased Treg numbers and FoxP3 expression. Additionally, Treg from aged mice also have greater ability to suppress effector T-cell (Teff) proliferation in vitro than Tregs from young mice. Tregs from aged mice exhibit greater redox remodeling-mediated suppression of Teff proliferation during coculture with DCs by decreasing extracellular cysteine availability to a greater extent than Tregs from young mice, creating an adverse environment for Teff proliferation. Tregs from aged mice produce higher IL-10 levels and suppress CD86 expression on DCs more strongly than Tregs from young mice, suggesting decreased T-cell activity. Taken together, these results reveal a potential mechanism of higher Treg-mediated activity that may contribute to increased immune suppression with age. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
Harada C.N.,Geriatrics Research |
Natelson Love M.C.,University of Alabama at Birmingham |
Triebel K.L.,University of Alabama at Birmingham
Clinics in Geriatric Medicine | Year: 2013
Even those who do not experience dementia or mild cognitive impairment may experience subtle cognitive changes associated with aging. Normal cognitive changes can affect an older adult's everyday function and quality of life, and a better understanding of this process may help clinicians distinguish normal from disease states. This article describes the neurocognitive changes observed in normal aging, followed by a description of the structural and functional alterations seen in aging brains. Practical implications of normal cognitive aging are then discussed, followed by a discussion of what is known about factors that may mitigate age-associated cognitive decline. © 2013.
Espinoza S.E.,Gerontology and Palliative Medicine |
Espinoza S.E.,University of Texas Health Science Center at San Antonio |
Espinoza S.E.,Geriatrics Research |
Hazuda H.P.,Clinical Epidemiology |
Hazuda H.P.,University of Texas Health Science Center at San Antonio
Journal of the American Geriatrics Society | Year: 2015
OBJECTIVES: To examine the association between neighborhood residence and frailty prevalence in older Mexican Americans (MAs). DESIGN: Cross-sectional, observational study. SETTING: Socioeconomically and ethnically diverse neighborhoods in San Antonio, Texas. PARTICIPANTS: Community-dwelling older MA adults (aged ≥65) who completed the baseline examination of the San Antonio Longitudinal Study of Aging (SALSA) (1992-1996) (N = 394). MEASUREMENTS: Subjects were randomly sampled from three types of neighborhoods that varied in ethnic composition and economic environment: barrio (low-income, exclusively MA), transitional (middle-income, equal proportion MAs and European Americans (EAs)) and suburban (upper-income, predominantly EA). Frailty was classified using the Fried criteria. Frailty odds were estimated according to neighborhood using logistic regression, with the suburban neighborhood as the reference category. Covariates included age, sex, diseases, depressive symptoms, and cognitive function. RESULTS: Frailty prevalence was 15.6% in the barrio, 9.4% in the transitional neighborhood, and 3.5% in the suburbs (P = .01). After adjusting for sociodemographic characteristics and disease covariates, odds of frailty were 4.15 times as high for MAs residing in the barrio as for those residing in the suburbs (P = .03). After adjustment for depression and cognition, this association was no longer significant. Diabetes mellitus and depression accounted for the higher odds of frailty in the barrio. Although odds of frailty in the transitional neighborhood were 1.95 times as high as those in the suburbs, the difference was not statistically significant. CONCLUSION: The ethnic composition and economic environment of the neighborhoods in which MA older adults reside are strongly associated with their odds of being frail. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.
Hung W.W.,Mount Sinai School of Medicine |
Hung W.W.,Geriatrics Research |
Egol K.A.,New York University |
Zuckerman J.D.,New York University |
And 2 more authors.
JAMA - Journal of the American Medical Association | Year: 2012
Hip fracture is a potentially devastating condition for older adults. Hip fracture leads to pain and immobilization with complications ranging from delirium to functional loss and death. Although a mainstay of treatment is orthopedic repair, a multidisciplinary comanagement approach, including medical specialistsandrehabilitation,maymaximizepatient recovery. Using the case of Mr W, an older man who sustained a fallandhip fracture,wepresent evidence-based components of care both in the hospital and outpatient settings. Preoperatively, clinicians should correct medical abnormalities and consider the appropriateness, timing, and type of surgical repair in the context of the patient's life expectancyandgoals of care. Perioperative careshouldinclude prophylaxis with antibiotics, chemoprophylaxis for venous thromboembolism, and correction of major clinical abnormalities prior to surgery. Pain control, delirium, and pressure ulcer prevention are important inpatient care elements. Multidisciplinary models incorporating these care elements can decrease complications during inpatient stay. Rehabilitation strategies should be tailored to patient needs; early mobilization followed by rehabilitation exercises in institutional, home, and group settings should be considered to maximize restoration of locomotive abilities. Attention to care transitions is necessary and treatment for osteoporosis should be considered. The road to recovery for hip fracture patients is long and most patientsmaynot regain their prefracture functional status. Understanding and anticipating issues that may arise in the older patient with hip fracture, while delivering evidence-based care components, is necessary to maximize patient recovery. ©2012 American Medical Association. All rights reserved.
Korenstein D.,Mount Sinai School of Medicine |
Keyhani S.,Mount Sinai School of Medicine |
Keyhani S.,Geriatrics Research |
Ross J.S.,Mount Sinai School of Medicine |
Ross J.S.,Geriatrics Research
Archives of Surgery | Year: 2010
Objectives: To explore attitudes of physicians from all specialties toward gifts from and interactions with the pharmaceutical and medical device industries. Design: Anonymous, cross-sectional survey distributed and collected between June 1 and September 1, 2008. Setting: Hospitals in the Mount Sinai School of Medicine consortium in the New York, New York, metropolitan area. Participants: Faculty and trainee physicians from all clinical departments. Main Outcome Measures: Attitudes toward industry interactions and gifts and their appropriateness measured on 4-point Likert scales. Results: A total of 590 physicians and medical students completed the survey (response rate,67.0%); 351 (59.5%) were male, 230 (39.0%) were attending physicians, and 131 (23.7%) of 553 (excluding medical students) were from surgical specialties. Attitudes toward industry and gifts were generally positive: 72.2% found sponsored lunches appropriate, whereas 25.4% considered large gifts appropriate. Surgeons, trainees, and those unfamiliar with institutional policies on industry interactions held more positive attitudes than others and were more likely to deem some gifts appropriate, including industry funding of residency programs and, among surgeons, receiving meals, travel expenses, and payments for attending lectures. Nonattending physicians held more positive attitudes toward receiving meals in clinical settings, textbooks, and samples. Conclusions: Physicians continue to hold positive attitudes toward marketing-oriented activities of the pharmaceutical and device industries. Changes in medical culture and physician education focused on surgeons and trainees may align physician attitudes with current policy trends. ©2010 American Medical Association. All rights reserved.
Ornstein K.A.,Mount Sinai School of Medicine |
Aldridge M.D.,Mount Sinai School of Medicine |
Garrido M.M.,Mount Sinai School of Medicine |
Garrido M.M.,Geriatrics Research |
And 4 more authors.
JAMA Internal Medicine | Year: 2015
IMPORTANCE Family caregivers of individuals with serious illness are at risk for depressive symptoms and depression. Hospice includes the provision of support services for family caregivers, yet evidence is limited regarding the effect of hospice use on depressive symptoms among surviving caregivers. OBJECTIVE To determine the association between hospice use and depressive symptoms in surviving spouses. DESIGN, SETTING, AND PARTICIPANTS We linked data from the Health and Retirement Study, a nationally representative longitudinal survey of community-dwelling US adults 50 years or older, to Medicare claims. Participants included a propensity score-matched sample of 1016 Health and Retirement Study decedents with at least 1 serious illness and their surviving spouses interviewed between August 2002 and May 2011.We compared the spouses of individuals enrolled in hospice with the spouses of individuals who did not use hospice, performing our analysis between January 30, 2014, and January 16, 2015. EXPOSURES Hospice enrollment for at least 3 days in the year before death. MAIN OUTCOMES AND MEASURES Spousal depressive symptom scores measured 0 to 2 years after death with the Center for Epidemiologic Studies Depression Scale, which is scored from 0 (no symptoms) to 8 (severe symptoms). RESULTS Of the 1016 decedents in the matched sample, 305 patients (30.0%) used hospice services for 3 or more days in the year before death. Of the 1016 spouses, 51.9% had more depressive symptoms over time (mean [SD] change, 2.56 [1.65]), with no significant difference related to hospice use. A minority (28.2%) of spouses of hospice users had improved Center for Epidemiologic Studies Depression Scale scores compared with 21.7%of spouses of decedents who did not use hospice, although the difference was not statistically significant (P = .06). Among the 662 spouses who were the primary caregivers, 27.3%of spouses of hospice users had improved Center for Epidemiologic Studies Depression Scale scores compared with 20.7%of spouses of decedents who did not use hospice; the difference was not statistically significant (P = .10). In multivariate analysis, the odds ratio for the association of hospice enrollment with improved depressive symptoms after the spouse's death was 1.63 (95%CI, 1.00-2.65). CONCLUSIONS AND RELEVANCE After bereavement, depression symptoms increased overall for surviving spouses regardless of hospice use. A modest reduction in depressive symptoms was more likely among spouses of hospice users than among spouses of nonhospice users.
Pappas S.S.,University of Michigan |
Leventhal D.K.,University of Michigan |
Albin R.L.,University of Michigan |
Albin R.L.,Geriatrics Research |
Dauer W.T.,University of Michigan
Current Topics in Developmental Biology | Year: 2014
This chapter focuses on neurodevelopmental diseases that are tightly linked to abnormal function of the striatum and connected structures. We begin with an overview of three representative diseases in which striatal dysfunction plays a key role-Tourette syndrome and obsessive-compulsive disorder, Rett's syndrome, and primary dystonia. These diseases highlight distinct etiologies that disrupt striatal integrity and function during development, and showcase the varied clinical manifestations of striatal dysfunction. We then review striatal organization and function, including evidence for striatal roles in online motor control/action selection, reinforcement learning, habit formation, and action sequencing. A key barrier to progress has been the relative lack of animal models of these diseases, though recently there has been considerable progress. We review these efforts, including their relative merits providing insight into disease pathogenesis, disease symptomatology, and basal ganglia function. © 2014 Elsevier Inc.
Kuchibhatla M.N.,Duke University |
Fillenbaum G.G.,Duke University |
Fillenbaum G.G.,Geriatrics Research
American Journal Geriatric Pharmacotherapy | Year: 2011
Objective: The objective of this article was to determine whether, in drug intervention trials, growth mixture modeling (GMM) is able to identify drug-responsive trajectory classes that are not evident in traditional growth modeling approaches. Methods: We reanalyzed acute phase (biweekly data up to 7 occasions) and longitudinal (12 months) data on the 469 patients in the SADHART-CHF study of the safety and efficacy of sertraline for depression in patients with heart failure. GMM was used to identify the trajectory classes present in the treatment and placebo groups, based on Hamilton Depression Rating Scale scores. Results:Two distinct trajectory classes were identified in the treatment group: (1) chronic depressives (12%), who remained depressed through the treatment phase; and (2) responders (88%), who had scores indicating nondepression at the conclusion of the acute phase. At baseline, chronic depressives were distinguished by higher Hamilton Depression Rating Scale scores, the presence of implantable cardioverter defibrillators, and a history of anxiety. During follow-up, they were more likely to have unstable angina. Only responders remitted (70%). Three distinct trajectories were identified in the placebo group: (1) moderating depressives (19%), (2) temporary improvers (13%), and (3) responders (68%). At baseline, the classes differed in mean Hamilton Depression Rating Scale scores, responders' scores falling between the other 2 classes, and the proportion with renal disease. Only remission differed at follow-up: responders (76%), moderating depressives (21%), and temporary improvers (3%). Where the traditional analytic approach found improvement from moderate to mild depression but no significant treatment effect, GMM found response in 20% more people in the treatment group than in the placebo group. Conclusions: Unlike conventionally used, standard analytic approaches, which focus on intervention impact at study end or change from baseline to study end, GMM enables maximum use of repeated data to identify unique trajectories of latent classes that are responsive to the intervention. ClinicalTrials.gov identifier: NCT00078286. © 2011 Elsevier HS Journals, Inc. All rights reserved.
Johnson K.S.,Duke University |
Johnson K.S.,Geriatrics Research
Journal of Palliative Medicine | Year: 2013
Racial and ethnic disparities in health care access and quality are well documented for some minority groups. However, compared to other areas of health care, such as disease prevention, early detection, and curative care, research in disparities in palliative care is limited. Given the rapidly growing population of minority older adults, many of whom will face advanced serious illness, the availability of high-quality palliative care that meets the varied needs of older adults of all races and ethnicities is a priority. This paper reviews existing data on racial and ethnic disparities in use of and quality of palliative care and outlines priorities for future research. © Copyright 2013, Mary Ann Liebert, Inc. 2013.
Valencia W.M.,Geriatrics Research |
Valencia W.M.,University of Miami |
Florez H.,Geriatrics Research |
Florez H.,University of Miami
Diabetes, Obesity and Metabolism | Year: 2014
The pharmacological management of diabetes in older people is complex and challenging. It requires a comprehensive understanding of the individual beyond the diabetes itself. Through the ageing years, the older individual presents with diabetes-related and non-related comorbidities and complications, develops functional limitations and psychological issues, and may lack social support and access to care. A disturbance in these categories, known as the four geriatric domains, will negatively affect diabetes self-management and self-efficacy, leading to poor outcomes and complications. Furthermore, older people with diabetes may be more interested in the management of other chronic conditions such as pain or impaired mobility, and diabetes may be lower in their list of priorities. Proper education must be provided to the older individual and caregivers, with continuous monitoring and counselling, especially when pharmacological interventions offer risks of side effects, adverse reactions and interactions with other medications. Informed shared medical decisions will help to improve adherence to the regimen; however, such discussions ought to be based on the best evidence available, which is unfortunately limited in this age group. We performed a review focused on pharmacological agents and summarize current evidence on their use for the treatment of diabetes in older people. We encourage clinicians to investigate and incorporate the four geriatrics domains in the selection and monitoring of these agents. © 2014 John Wiley & Sons Ltd.