Showing papers in "Journals of Gerontology Series A-biological Sciences and Medical Sciences in 2008"

ELISA and multiplex technologies for cytokine measurement in inflammation and aging research.

Abstract: Over the last decade there has been an enormous expansion of research focused on defining the role of inflammation in aging, age-related diseases, disability, and frailty. The availability of methods to measure cytokines and other inflammatory mediators or markers with high sensitivity and specificity is critically important. Enzyme-linked immunosorbent assay (ELISA), the most widely used and best validated method, is limited by its ability to measure only a single protein in each sample. Recent developments in serum cytokine quantification technology include multiplex arrays, which offer the potential of better evaluating the complexity and dynamic nature of inflammatory responses and offer substantial cost and sample savings over traditional ELISA measurements. Despite potential advantages of this new technology, experience with these techniques is limited, and it has not emerged to date as the gold standard in inflammatory mediator measurement. This article reviews ELISA and the emerging multiplex technologies, compares the cost and effectiveness of recently developed multiplex arrays with traditional ELISA technology, and provides specific recommendations for investigators interested in measuring serum inflammatory mediators in older adults.

Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence.

Abstract: Deficits in cholinergic function have been postulated to cause delirium and cognitive decline. This review examines current understanding of the cholinergic deficiency hypothesis in delirium by synthesizing evidence on potential pathophysiological pathways. Acetylcholine synthesis involves various precursors, enzymes, and receptors, and dysfunction in these components can lead to delirium. Insults to the brain, like ischemia and immunological stressors, can precipitously alter acetylcholine levels. Imbalances between cholinergic and other neurotransmitter pathways may result in delirium. Furthermore, genetic, enzymatic, and immunological overlaps exist between delirium and dementia related to the cholinergic pathway. Important areas for future research include identifying biomarkers, determining genetic contributions, and evaluating response to cholinergic drugs in delirium. Understanding how the cholinergic pathway relates to delirium may yield innovative approaches in the diagnosis, prevention, and treatment of this common, costly, and morbid condition.

Functional Impact of 10 Days of Bed Rest in Healthy Older Adults

Abstract: Background. Many older individuals decline functionally during hospitalization, and the deleterious consequences of bed rest may be one cause. This study reports on the effect of 10 days of bed rest on multiple functional parameters in healthy older adults. Methods. Healthy older men and women (n ¼ 11, 67 6 5 years old) remained on bed rest for 10 days continuously, and consumed a eucaloric diet providing the Recommended Dietary Allowance for protein. Measures of lower extremity strength and power, aerobic capacity and physical performance, as well as physical activity were performed before and after bed rest. Results. All measures of lower extremity strength were significantly lower after bed rest including isotonic knee extensor strength (� 13.2 6 4.1%, p ¼ .004) and stair-climbing power (� 14 6 4.1%, p ¼ .01). Maximal aerobic capacity was 12% lower after bed rest (p ¼ .04), whereas measures of physical performance (Short Physical Performance Battery, and a five-item physical performance test) were not significantly different. Voluntary physical activity decreased after bed rest, and the percentage of time spent inactive increased (7.6 6 1.8%, p ¼ .004). There were no medical complications. Conclusions. In healthy older adults, 10 days of bed rest results in a substantial loss of lower extremity strength, power, and aerobic capacity, and a reduction in physical activity, but has no effect on physical performance. Identification of interventions to maintain muscle function during hospitalization or periods of bed rest in older adults should be a high priority.

Initial Manifestations of Frailty Criteria and the Development of Frailty Phenotype in the Women's Health and Aging Study II

Abstract: Background. Understanding points of onset of the frailty syndrome is vital to early identification of at-risk individuals and to targeting intervention efforts to those components that are first affected, when reversal may be most possible. This study aims to characterize natural history by which commonly used frailty criteria manifest and to assess whether the rate of progression to frailty depends on initial manifestations. Methods. The investigation was based on a 7.5-year observational study of 420 community-dwelling women aged 70–79 years who were not frail at baseline, with frailty defined as meeting � 3 of 5 criteria: weight loss, slow walking speed, weakness, exhaustion, and low physical activity level. Results. The 7.5-year incidence of frailty was 9% among women who were nonfrail at baseline. Despite significant heterogeneity, weakness was the most common first manifestation, and occurrence of weakness, slowness, and low physical activity preceded exhaustion and weight loss in 76% of the women who were nonfrail at baseline. Women with exhaustion or weight loss as initial presenting symptoms were 3–5 times more likely to become frail than were women without any criterion (p , .05). Conclusions. Our findings suggest that weakness may serve as a warning sign of increasing vulnerability in early frailty development, and weight loss and exhaustion may help to identify women most at risk for rapid adverse progression.

Dual-Task Decrements in Gait: Contributing Factors Among Healthy Older Adults

Abstract: Background. The factors that contribute to the dual tasking (DT) changes in performance that occur when older adults walk while simultaneously performing other tasks are not well known. We hypothesized that cognitive and motor reserve (e.g., executive function [EF], postural control, and walking abilities) and affect (e.g., anxiety, depressive symptoms) influence the DT decrements (DTDs) in gait. Methods. Two hundred twenty-eight community-living, healthy older adults (mean: 76.2 6 4.2 years; 59% women) walked with and without DT, for example, subtracting 7s and phoneme monitoring. Mobility (e.g., the Dynamic Gait Index), cognitive function (e.g., memory, EF), and affect (e.g., Geriatric Depression Scale) were quantified. Bivariate and multivariate analyses identified factors associated with the DTD in gait speed (a general measure of locomotor function), swing time, (reflecting balance during gait), and swing time variability (a measure of stride-to-stride consistency). Results. Gait speed and swing time decreased (p , .001) and swing time variability increased (became worse) (p , .001) during all DTs. The DTD in gait speed was correlated with comfortable walking gait speed, but not with tests of mobility or cognitive function. The DTD in swing time variability was correlated with EF, mobility, and affect (e.g., depressive symptoms). Much of the variance in the DTDs was unexplained. Conclusions. Usual walking abilities and cognitive function contribute to the DT effects on gait, but these relationships depend on specifics of the DT, the gait feature being studied, and the particulars of the cognitive domain. Meeting the everyday challenges of walking while dual tasking apparently relies on multiple factors including a consistent gait pattern and EF.

Frailty Among Community-Dwelling Elderly People in France: The Three-City Study

Abstract: BACKGROUND: To better understand the contribution of frailty to health-related outcomes in elderly persons, it seems valuable to explore data from cohort studies across the world in an attempt to establish a comprehensive definition. The purpose of this report is to show the characteristics of frailty and observe its prognosis in a large sample of French community-dwelling elderly persons. METHODS: We used data from 6078 persons 65 years old or older participating in the Three-City Study (3C). Frailty was defined as having at least three of the following criteria: weight loss, weakness, exhaustion, slowness, and low activity. Principal outcomes were incident disability, hospitalization, and death. Multiple covariates were used to test the predictive validity of frailty on these outcomes. RESULTS: Four hundred twenty-six individuals (7%) met frailty criteria. Participants classified as frail were significantly older, more likely to be female, and less educated and reported more chronic diseases, lower income, and poorer self-reported health status in comparison to nonfrail participants. In multivariate analysis, frailty was significantly associated with 4-year incidence of disability in activities of daily living (ADL) and instrumental ADL. However, frailty was marginally associated with incident hospitalization and was not a statistically significant predictor of incident mobility disability or mortality adjusting for potential confounding factors. CONCLUSIONS: Frailty is not specific to a subgroup or region of the world. The construct proposed by Fried and colleagues confirms its predictive validity for adverse-health outcomes, particularly for certain components of disability, thus suggesting that it may be useful in population screening and predicting service needs.

Life Course Social and Health Conditions Linked to Frailty in Latin American Older Men and Women

Abstract: Background Gender, social conditions, and health throughout the life course affect functional health in later life. This article addresses two specific hypotheses: i) life-course social and health conditions are associated with frailty; and ii) differential exposure and/or vulnerability of women and men to life-course conditions may account for gender differences in frailty. Methods Data originated from a cross-national survey of older adults living in five large Latin American cities. Frailty was defined as the presence of three or more of five criteria: unintentional weight loss (10 pounds during the past year), self-reported exhaustion/poor endurance, weakness (grip strength), limitations in lower extremities, and low physical activity; a prefrail state was defined as the presence of one or two of the above criteria. Associations between frailty and social and health indicators were examined using a proportional odds ordinal logistic regression. Results Prevalence of frailty varied from 0.30 to 0.48 in women and from 0.21 to 0.35 in men. Childhood (hunger, poor health, and poor socioeconomic conditions), adulthood (little education and non-white-collar occupation), and current social conditions (insufficient income) were associated with higher odds of frailty in both men and women. Comorbidity and body mass index were related to frailty, but their effects differed in women and men. Male/female age-adjusted odds of frailty varied from 1.55 (Bridgetown) to 2.77 (Havana). Differential exposure and vulnerability partially explained differences between women and men. Conclusion Theoretical models to explain gender and social differences in frailty should use a life-course perspective.

Force Platform Balance Measures as Predictors of Indoor and Outdoor Falls in Community-Dwelling Women Aged 63–76 Years

Abstract: Background. Inability to maintain balance while standing increases risk of falls in older people. The present study assessed whether center of pressure (COP) movement measured with force platform technology predicts risk for falls among older people with no manifest deficiency in standing balance. Methods. Participants were 434 community-dwelling women, aged 63-76 years. COP was measured in six stances on a force platform. Following balance tests, participants reported their falls with 12 monthly calendars. Incidence rate ratios (IRR) with 95% confidence intervals (CI) were computed from negative binomial regression models. For the analysis, those with>/=1 fall indoors were coded"indoor fallers,"those with>/=1 fall outdoors, but no indoor falls, were coded"outdoor fallers."Outcome in the models was number of falls. Analyses were repeated including only participants without fall history prior to follow-up. Results. Among 198 fallers, there were 57 indoor and 132 outdoor fallers. The participants in the highest COP movement tertile, irrespective of the balance test, had a two- to fourfold risk for indoor falls compared to participants in the lowest COP tertile of the test. Inability to complete the tandem stance was also a significant predictor of the fall risk. The trend for increased risk for indoor falls was found also for participants in the highest COP movement tertile and without fall history. The COP movement in balance tests was not associated with outdoor falls. Conclusion. Force platform balance tests provide valid information of postural control that can be used to predict fall risk even among older people without apparent balance problems or fall history. When the force platform is not available, tandem stance provides a screening tool to show increased fall risk in community-dwelling older people. Language: en

Physical Exercise at Midlife and Risk of Dementia Three Decades Later: A Population-Based Study of Swedish Twins

Abstract: Background With the number of people with dementia increasing, identifying potential protective factors has become more important. We explored the association between physical exercise at midlife and subsequent risk of dementia among members of the HARMONY study. Methods Measures of exercise were obtained by the Swedish Twin Registry an average of 31 years prior to dementia assessment. Dementia was diagnosed using a two-stage procedure--screening for cognitive impairment followed by full clinical evaluation. We used two study designs: case-control analyses included 264 cases with dementia (176 had Alzheimer's disease) and 2870 controls; co-twin control analyses included 90 twin pairs discordant for dementia. Results In case-control analyses, controlling for age, sex, education, diet (eating fruits and vegetables), smoking, drinking alcohol, body mass index, and angina, light exercise such as gardening or walking and regular exercise involving sports were associated with reduced odds of dementia compared to hardly any exercise (odds ratio [OR] = 0.63, 95% confidence interval [CI], 0.43-0.91 for light exercise; OR = 0.34, 95% CI, 0.16-0.72 for regular exercise). Findings were similar for Alzheimer's disease alone. In co-twin control analyses, controlling for education, the association between higher levels of exercise and lower odds of dementia approached significance (OR = 0.50, 95% CI, 0.23-1.06; p =.072). Conclusions Exercise at midlife may reduce the odds of dementia in older adulthood, suggesting that exercise interventions should be explored as a potential strategy for delaying disease onset.

Strength Versus Muscle Power-Specific Resistance Training in Community-Dwelling Older Adults

Abstract: Background. Loss of muscle power due to normal aging has greater functional impact than loss of strength alone. The present study compared two resistance training programs, one aimed at enhancing muscle power and one at increasing muscle strength, on muscle function and functional performance in older adults. Methods. Sixty-seven healthy, independent older adults (65‐84 years) were randomized to a high-velocity varied resistance (HV), constant resistance (ST), or nontraining control (CO) group. Participants trained twice weekly for 24 weeks using six exercises. Dynamic and isometric muscle strength, muscle power, movement velocity, muscle endurance, and a battery of functional performance tasks were assessed. Secondary outcomes included body composition, quality of life, and balance confidence. Results. Muscle strength increased significantly ( p , .001) and similarly in the training groups compared to controls (HV, 51.0 6 9.0%; ST, 48.3 6 6.8%; CO, 1.2 6 5.1%). Peak muscle power also increased with training ( p , .05), with no difference between training groups. The change in peak power was 50.5 6 4.1%, 33.8 6 3.8%, and � 2.5 6 3.9% in the HV, ST, and CO groups, respectively. Training also improved selected functional performance tasks in the HV and ST groups compared to controls ( p , .05), and the HV group reported improved quality of life ( p ¼ .018). Conclusion. Muscle power and muscle strength improved similarly using either resistance training protocol, and these changes were accompanied by improvements in several functional performance tasks. However, improvements in the HV group occurred with less total work performed per training session.

Multidimensional preventive home visit programs for community-dwelling older adults: a systematic review and meta-analysis of randomized controlled trials.

Abstract: BACKGROUND: Multidimensional preventive home visit programs aim at maintaining health and autonomy of older adults and preventing disability and subsequent nursing home admission, but results of randomized controlled trials (RCTs) have been inconsistent. Our objective was to systematically review RCTs examining the effect of home visit programs on mortality, nursing home admissions, and functional status decline. METHODS: Data sources were MEDLINE, EMBASE, Cochrane CENTRAL database, and references. Studies were reviewed to identify RCTs that compared outcome data of older participants in preventive home visit programs with control group outcome data. Publications reporting 21 trials were included. Data on study population, intervention characteristics, outcomes, and trial quality were double-extracted. We conducted random effects meta-analyses. RESULTS: Pooled effects estimates revealed statistically nonsignificant favorable, and heterogeneous effects on mortality (odds ratio [OR] 0.92, 95% confidence interval [CI], 0.80-1.05), functional status decline (OR 0.89, 95% CI, 0.77-1.03), and nursing home admission (OR 0.86, 95% CI, 0.68-1.10). A beneficial effect on mortality was seen in younger study populations (OR 0.74, 95% CI, 0.58-0.94) but not in older populations (OR 1.14, 95% CI, 0.90-1.43). Functional decline was reduced in programs including a clinical examination in the initial assessment (OR 0.64, 95% CI, 0.48-0.87) but not in other trials (OR 1.00, 95% CI, 0.88-1.14). There was no single factor explaining the heterogenous effects of trials on nursing home admissions. CONCLUSION: Multidimensional preventive home visits have the potential to reduce disability burden among older adults when based on multidimensional assessment with clinical examination. Effects on nursing home admissions are heterogeneous and likely depend on multiple factors including population factors, program characteristics, and health care setting.

The Baltimore Longitudinal Study of Aging (BLSA): a 50-year-long journey and plans for the future.

Abstract: W ITH these words, President Dwight D. Eisenhower announced the creation of the National Aeronautics and Space Administration on March 26, 1958, thereby launching a project that, in a little over a decade, would bring humankind to walk on the moon. While every American watched the unfolding of this adventure into outer space with enthusiasm and trepidation, scientists at the National Institutes of Health (NIH) were beginning a different journey, perhaps less glamorous and far from the clamor of the media, but certainly no less important for humankind. That same momentous year, the foundation for another milestone was being poured when Nathan Shock, William W. Peter, and Arthur Norris at the National Institute on Aging advanced the idea that the aging process would be better understood by studying the same individuals throughout their life span, collecting serial assessments at multiple time points rather than by comparing individuals of different ages who may have been exposed to different historical events and environmental conditions. Although the idea of longitudinal study was not completely new, it was the first time that it was applied to the study of aging. The NIH group called for volunteers to join the Baltimore Longitudinal Study of Aging (BLSA), remain in the study throughout the rest of their lives, and donate their bodies to science after their death. While today, this study design appears straightforward, in 1958, the notion of following individuals for life to study aging was an extraordinary leap forward in the field, a jump that would transform aging research forever. Although questions about the nature of the aging process are probably as old as humankind, never before had anyone postulated that chronological and biological age could be dissected, and that aging and pathology may evolve along separate, although somewhat parallel, pathways. Today, 50 years later, the BLSA is one of the largest and longest-running longitudinal studies of aging in the United States and is still addressing the same question. What a vision! Over many years, the BLSA has made major contributions to our understanding of normal aging in humans. I cannot even begin to summarize here the fruits of 50 years of labor, hundreds of scientific publications, and generous contributions of more than 3000 participants. This is common knowledge. Data from the BLSA have helped scientists explore age-associated changes in anatomical integrity and function across all physiological systems, including musculoskeletal, cardiovascular, endocrine, and renal, just to name a few examples (1–4). By analyzing long-term personality data, BLSA scientists were able to refute the popular belief that, as people age, they become irritable and sad, and found that, in fact, personality doesn’t change much after puberty (1,5). By exploring how the ability to think, learn, and remember changes over time in specific BLSA participants, scientists were able to show that those who experienced an accelerated decline in memory, verbal intelligence, and executive function were more likely to develop dementia (6). Above all, the BLSA indicated that, although aging and longevity are affected by genetic factors, the quality of our own aging is strongly affected by following a few simple rules, such as watching our weight and waist, eating a healthy diet, exercising regularly, and maintaining an active role in society (1,7–16). Curiously, the BLSA has both rewarded and, in some sense, disappointed the scientists who designed it. There is absolutely no doubt that most of the deterioration in physiological, physical, and cognitive function that occurs in many aging individuals is attributable to disease, suggesting that perhaps aging and diseases evolve along separate biological paths. However, as medical technology has advanced, and measurement tools have become more precise and accurate, the line of demarcation between aging and disease has started to blur (2). Subtle structural and functional changes that previously escaped the ‘‘pathology’’ filter are now considered (subclinical) risk factors for diseases (17–19). We are discovering that aging is a progressive dysregulation of our homeostatic network, and that life is maintained owing to the incredible adaptability and resiliency that the network allows at all levels of integration, from mitochondrial function to societal and community adaptations. This circuitry of signals, receptors, and effectors is extremely complex because of the need to detect and characterize thousands of different stressors and build the most effective, rapid, and parsimonious homeostatic response (20). There is evidence that, with aging, this

Executive Functions Are Associated With Gait and Balance in Community-Living Elderly People

Abstract: Background. Cognition influences gait and balance in elderly people. Executive functions seem to play a key role in this mechanism. Previous studies used only a single test to probe executive functions, and outcome measures were restricted to gait variables. We extend this prior work by examining the association between two different executive functions and measures of both gait and balance, with and without two different cognitive dual tasks. Methods. This is a cross-sectional study with randomly selected community-living elderly people. Executive functions were tested with the Trail Making Test Parts A and B and the Stroop Color Word Test; memory with Cambridge Neuropsychological Test Automated Battery (CANTAB) subtests. Patients walked without and with two dual tasks (subtracting serial sevens and animal naming). Main outcomes focused on gait (velocity, stride length, and stride time variability), measured on an electronic walkway, and balance, measured as trunk movements during walking. Associations were assessed with multiple regression models. Results. One hundred elderly people, with a mean age 80.6 years (range 75–93 years) participated. Both dual tasks decreased gait velocity and increased variability and trunk sway. Executive functions were associated with only stride length variability and mediolateral trunk sway during performance of animal naming as the dual task. Memory was not associated with the gait and balance variables. Conclusions. In community-living elderly people, executive functions are associated with gait and balance impairment during a challenging dual-task condition that also depends on executive integrity. Next steps will be to explore the value of executive functions in defining fall-risk profiles and in fall-prevention interventions for frail patients.

Special Article Gait Measures Indicate Underlying Focal Gray Matter Atrophy in the Brain of Older Adults

Abstract: THERE is consistent evidence that older adults experiencing mobility impairment are more likely to have underlying impairment in the structure (1-10) and function (11-14) of the brain. Previous brain-imaging studies of older adults have shown that global brain atrophy and white matter hyperintensities (WMHs) within the connections that spread around the ventricles and under the frontal cortex are associated with clinical measures of poor balance and slow gait (2,4-7,15-17) and also with longer double support time (10). We have also shown that brain infarcts, mostly located in the basal ganglia (10), are associated with shorter steps. These previous imaging studies relied on semiquantitative estimates of diffuse brain structural changes rather than on quantitative measures of focal and region-specific abnormalities. The measures of overall brain volume and diffuse WMHs are not specific for mobility impairment, and they are associated with changes in several other functional domains besides mobility (e.g., with mood and cognition). The objective of this study is to identify the spatial distribution of focal, region-specific neuronal loss in association with individual quantitative gait characteristics independently of other risk factors of gait abnormalities, including peripheral (peripheral neuropathy, obesity, or arthritis) and central (markers of diffuse brain structural abnormalities and cognitive function measures) risk factors. Aside from studies conducted in patient populations with overt neurological diseases, the spatial distribution of region-specific abnormalities associated with individual characteristics of gait has not been well explored in community-dwelling older adults. Our recent region-specific volumetric study suggested the presence of such spatial distribution for crude measures of mobility, such as gait speed and difficulty holding the semitandem stand (18), but it did not examine the relationship with distinct, quantitative measures of spatial and temporal gait characteristics. In this study, we measure the association between the gray matter volume of individual brain regions and spatial (step width, step length) and temporal (double support time, stance time, step time) characteristics of gait. We hypothesize that wider steps, which are related to balance control (19), are associated with smaller volumes of regions important for balance regulation (basal ganglia and cerebellum). Based on evidence from previous studies (2,4-7,10,15-17), we hypothesize that longer steps are associated with smaller volumes in the basal ganglia and with regions connected to these via the cortico-striato-thalamic loops (primary motor and sensorimotor regions) and that double support time is associated with those regions that are connected through the periventricular cortico-thalamic connections (thalamus, primary motor, and sensorimotor regions). In secondary analyses, we examine the associations with regions important for visuospatial attention (inferior and superior posterior parietal lobules; 20), cognitive processing speed/executive control function (dorsolateral prefrontal cortex [dLPFC]), memory (hippocampus), and motor imagery (precuneus, posterior cingulated cortex, parahippocampus). Finally, we test the hypothesis that the association between brain regions and gait characteristics is partially explained by lower scores on the Digit Symbol Substitution Test (DSST), a test of visuospatial attention and cognitive processing speed. The rationale for this hypothesis is that lower scores on executive control function tests are associated with structural and functional abnormalities of these regions and also with gait.

Effects of Moderate-Intensity Exercise on Polysomnographic and Subjective Sleep Quality in Older Adults With Mild to Moderate Sleep Complaints

Abstract: Background. This study sought to determine the 12-month effects of exercise increases on objective and subjective sleep quality in initially inactive older persons with mild to moderate sleep complaints. Methods. A nonclinical sample of underactive adults 55 years old or older (n ¼ 66) with mild to moderate chronic sleep complaints were randomly assigned to a 12-month program of primarily moderate-intensity endurance exercise (n ¼ 36) or a health education control program (n ¼ 30). The main outcome measure was polysomnographic sleep recordings, with additional measures of subjective sleep quality, physical activity, and physical fitness. Directional hypotheses were tested. Results. Using intent-to-treat methods, at 12 months exercisers, relative to controls, spent significantly less time in polysomnographically measured Stage 1 sleep (between-arm difference ¼ 2.3, 95% confidence interval [CI], 0.7‐4.0; p ¼ .003), spent more time in Stage 2 sleep (between-arm difference ¼ 3.2, 95% CI, 0.6‐5.7; p ¼ .04), and had fewer awakenings during the first third of the sleep period (between-arm difference ¼ 1.0, 95% CI, 0.39‐1.55; p ¼ .03). Exercisers also reported greater 12-month improvements relative to controls in Pittsburgh Sleep Quality Index (PSQI) sleep disturbance subscale score (p ¼ .009), sleep diary‐based minutes to fall asleep (p ¼ .01), and feeling more rested in the morning (p ¼ .02). Conclusions. Compared with general health education, a 12-month moderate-intensity exercise program that met current physical activity recommendations for older adults improved some objective and subjective dimensions of sleep to a modest degree. The results suggest additional areas for investigation in this understudied area.

Early effects of "Guided Care" on the quality of health care for multimorbid older persons: a cluster-randomized controlled trial.

Abstract: Background. The quality of health care for older Americans with multiple chronic conditions is suboptimal. We designed ‘‘Guided Care’’ (GC) to enhance quality of care by integrating a registered nurse, intensively trained in chronic care, into primary care practices to work with physicians in providing comprehensive chronic care to 50–60 multimorbid older patients. Methods. We hypothesized that GC would improve the quality of health care for this population. In 2006, we began a cluster-randomized controlled trial of GC at eight practices (n ¼ 49 physicians). Older patients of these practices were eligible to participate if they were at risk for using health services heavily during the coming year. Teams of two to five physicians and their at-risk older patients were randomized to either GC or usual care (UC). Six months after baseline, participants rated the quality of their health care by answering validated closed-ended questions from telephone interviewers who were masked to group assignment. Results. Of the 13,534 older patients screened, 2391 (17.7%) were eligible to participate in the study, of which 904 (37.8%) gave informed consent and were cluster-randomized. After 6 months, 93.8% and 93.2% of the GC and UC participants who remained alive and eligible completed telephone interviews. GC participants were more likely than UC participants to rate their care highly (adjusted odds ratio ¼ 2.0, 95% confidence interval, 1.2-3.4, p ¼ .006), and primary care physicians were more likely to be satisfied with their interactions with chronically ill older patients and their families (p , .05). Conclusions. GC improves important aspects of the quality of health care for multimorbid older persons. Additional data will become available as this trial continues.

The Association of Race, Gender, and Comorbidity With Mortality and Function After Hip Fracture

Abstract: BACKGROUND: Few studies of hip fracture have large enough samples of men, minorities, and persons with specific comorbidities to examine differences in their mortality and functional outcomes. To address this problem, we combined three cohorts of hip fracture patients to produce a sample of 2692 patients followed for 6 months. METHOD: Data on mortality, mobility, and other activities of daily living (ADLs) were available from all three cohorts. We used multiple regression to examine the association of race, gender, and comorbidity with 6-month survival and function, controlling for prefracture mobility and ADLs, age, fracture type, cohort, and admission year. RESULTS: The mortality rate at 6 months was 12%: 9% for women and 19% for men. Whites and women were more likely than were nonwhites and men to survive to 6 months, after adjusting for age, comorbidities, and prefracture mobility and function. Whites were more likely than were nonwhites to walk independently or with help at 6 months compared to not walking, after adjusting for age, comorbidities, and prefracture mobility and function. Dementia had a negative impact on survival, mobility, and ADLs at 6 months. The odds of survival to 6 months were significantly lower for people with chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), and/or cancer. Parkinson's disease and stroke had negative impacts on mobility and ADLs, respectively, among survivors at 6 months. CONCLUSIONS: The finding of higher mortality and worse mobility for nonwhite patients with hip fractures highlights the need for more research on race/ethnicity disparities in hip fracture care. Language: en

Does a Geriatric Oncology Consultation Modify the Cancer Treatment Plan for Elderly Patients

Abstract: Background This study was performed to describe the treatment plan modifications after a geriatric oncology clinic Assessment of health and functional status and cancer assessment was performed in older cancer patients referred to a cancer center Patients and methods Between June 2004 and May 2005, 105 patients 70 years old or older referred to a geriatric oncology consultation at the Institut Curie cancer center were included Functional status, nutritional status, mood, mobility, comorbidity, medication, social support, and place of residence were assessed Oncology data and treatment decisions were recorded before and after this consultation Data were analyzed for a possible correlation between one domain of the assessment and modification of the treatment plan Results Patient characteristics included a median age of 79 years and a predominance of women with breast cancer About one half of patients had an independent functional status Nearly 15% presented severe undernourishment Depression was suspected in 531% of cases One third of these patients had >2 chronic diseases, and 74% of patients took > or =3 medications Of the 93 patients with an initial treatment decision, the treatment plan was modified for 387% of cases after this assessment Only body mass index and the absence of depressive symptoms were associated with a modification of the treatment plan Conclusion The geriatric oncology consultation led to a modification of the cancer treatment plan in more than one third of cases Further studies are needed to determine whether these modifications improve the outcome of these older patients

The Physical and Biological Characterization of a Frail Mouse Model

Abstract: Background. The development of animal models that approximate human frailty is necessary to facilitate etiologic and treatment-focused frailty research. The genetically altered IL-10 tm/tm mouse does not express the antiinflammatory cytokine interleukin 10 (IL-10) and is, like frail humans, more susceptible to inflammatory pathway activation. We hypothesized that with increasing age, IL-10 tm/tm mice would develop physical and biological characteristics similar to those of human frailty as compared to C57BL/6J control mice. Methods. Strength, activity, serum IL-6, and skeletal muscle gene expression were compared between age-matched and gender-matched IL-10 tm/tm mice on C57BL/6J background and C57BL/6J control mice using a longitudinal design for physical characteristics and cross-sectional design for biological characteristics. Results. Strength levels declined significantly faster in IL-10 tm/tm compared to control mice with increasing age. Serum IL-6 levels were significantly higher in older compared to younger IL-10 tm/tm mice and were significantly higher in older IL-10 tm/tm compared to age- and gender-matched C57BL/6J control mice. One hundred twenty-five genes, many related to mitochondrial biology and apoptosis, were differentially expressed in skeletal muscle between 50-week-old IL-10 tm/tm and 50-week-old C57BL/6J mice. No expression differences between IL-10 tm/tm age groups were identified by quantitative polymerase chain reaction. Conclusion. These physical and biological findings suggest that the IL-10 tm/tm mouse develops inflammation and strength decline consistent with human frailty at an earlier age compared to C57BL/6J control type mice. This finding provides rationale for the further development and utilization of the IL-10 tm/tm mouse to study the biological basis

A randomized study of a multidisciplinary program to intervene on geriatric syndromes in vulnerable older people who live at home (Dutch EASYcare Study).

Abstract: Background The effectiveness of community-based geriatric intervention models for vulnerable older adults is controversial We evaluated a problem-based multidisciplinary intervention targeting vulnerable older adults at home that promised efficacy through better timing and increased commitment of patients and primary care physicians This study compared the effects of this new model to usual care Methods Primary care physicians referred older people for problems with cognition, nutrition, behavior, mood, or mobility One hundred fifty-one participants (mean age 822 years, 748% women) were included in a pseudocluster randomized trial with 6-month follow-up for the primary outcomes Eighty-five participants received the new intervention, and 66 usual care In the intervention arm, geriatric nurses visited patients at home for geriatric assessment and management in cooperation with primary care physicians and geriatricians Modified intention-to-treat analyses focused on differences between treatment arms in functional abilities (Groningen Activity Restriction Scale-3) and mental wellbeing (subscale mental health Medical Outcomes Study [MOS]-20), using a mixed linear model Results After 3 months, treatment arms showed significant differences in favor of the new intervention Functional abilities improved 22 points (95% confidence interval [CI], 03–42) and well-being 58 points (95% CI, 01–114) After 6 months, the favorable effect increased for well-being (91; 95% CI, 24–159), but the effect on functional abilities was no longer significant (16; 95% CI, � 07 to 39) Conclusions This problem-based geriatric intervention improved functional abilities and mental well-being of vulnerable older people Problem-based interventions can increase the effectiveness of primary care for this population

Chemokines Are Associated With Delirium After Cardiac Surgery

Abstract: Background Delirium has been hypothesized to be a central nervous system response to systemic inflammation during a state of blood brain barrier compromise. The purpose of this study was to compare postoperative changes in groups of inflammatory markers in subjects who developed delirium following cardiac surgery and matched controls without delirium.

Higher Levels and Blunted Diurnal Variation of Cortisol in Frail Older Women

Abstract: Background Frailty is an important geriatric condition with increased vulnerability to stressors (e.g., infection and injury) and for developing functional dependence and mortality. Impairments in signaling pathways, including neuroendocrine alterations, are thought to be involved in the etiology of frailty, but have not been well characterized to date. We evaluated whether higher levels and blunted diurnal variation of salivary cortisol are cross-sectionally associated with frailty burden. Methods Two hundred fourteen community-dwelling women, 80-90 years old, from the Women's Health and Aging Study participated in this study between 2004 and 2005. Seven saliva samples were collected for cortisol measurement over a 24-hour period. Main outcomes were awakening, evening, and overall mean cortisol; diurnal amplitude; and rate of decline of cortisol level during morning hours. All cortisol concentrations were log-transformed. Frailty burden was calculated, based on a previously validated tool, as the number (0-5) of the following criteria present: weakness, exhaustion, weight loss, slowness, and inactivity. Results Significant positive associations were found between frailty burden and evening cortisol (beta = 0.11, p =.04), and between frailty burden and 24-hour mean cortisol (beta = 0.07, p =.03). Increasing frailty burden was significantly associated with smaller declines in cortisol during morning hours (beta = 0.04, p =.02). Frailty burden of > or =2 was associated with a smaller diurnal amplitude (beta = -0.34, p =.03). Awakening cortisol was not significantly associated with frailty burden (beta = 0.01, p =.8). All analyses included adjustments for several important confounders. Conclusions Our findings provide the first epidemiological evidence that higher levels and blunted diurnal variation of cortisol may be involved in the vulnerability and clinical presentation observed in frail older women.

Performance-Based Functional Assessment in Older Hospitalized Patients: Feasibility and Clinical Correlates

Abstract: Background. Functional evaluation is a cornerstone of multidimensional geriatric assessment; however, little is known of the clinical value of standardized performance-based assessment in the acute care setting. The aim of this study was to evaluate the clinical correlates and short-term predictive value of the Short Physical Performance Battery (SPPB) in older patients admitted to the hospital for an acute medical event. Methods. We enrolled 92 women and men 65 years old or older who were able to walk, who had a Mini-Mental State Examination (MMSE) score � 18, and who were admitted to the hospital with a clinical diagnosis of congestive heart failure, pneumonia, chronic obstructive pulmonary disease (COPD), or minor stroke. The SPPB was assessed at hospital admission and discharge. Self-report functional assessment included basic activities of daily living (ADL) and instrumental activities of daily living (IADL). Spearman’s rank correlation coefficients and multivariable linear regression analyses were used to study the association of SPPB score and functional and clinical characteristics, including length of hospital stay. Results. The mean age was 77.7 years (range 65–94 years), 49% were female, 64.1% had congestive heart failure, 16% COPD, 13.1% pneumonia, and 6.5% minor stroke. At hospital admission the mean SPPB score was 6.0 6 2.7. SPPB scores were inversely correlated with age, the severity of the index disease, and IADL and ADL difficulty 2 weeks before hospital admission (p , .01), and were directly correlated with MMSE score (p ¼ .002). On average, SPPB score increased 1 point (þ0.97, standard error of the mean ¼ 0.2; p for paired t test , .001) from baseline to hospital discharge assessment. After adjustment for potential confounders, baseline SPPB score was significantly associated with the length of hospital stay (p , .007). Conclusion. In older acute care inpatients, SPPB is a valid indicator of functional and clinical status. SPPB score at hospital admission is an independent predictor of the length of hospital stay.

Second and third generation assessment instruments: the birth of standardization in geriatric care

Abstract: The systematic adoption of "second-generation" comprehensive geriatric assessment instruments, initiated with the Minimum Data Set (MDS) implementation in U.S. nursing homes, and continued with the uptake of related MDS instruments internationally, has contributed to the creation of large patient-level data sets. In the present special article, we illustrate the potential of analyses using the MDS data to: (a) identify novel prognostic factors; (b) explore outcomes of interventions in relatively unselected clinical populations; (c) monitor quality of care; and (d) conduct comparisons of case mix, outcomes, and quality of care. To illustrate these applications, we use a sample of elderly patients admitted to home care in 11 European Home Health Agencies that participated in the AgeD in HOme Care (AD-HOC) project, sponsored by the European Union. The participants were assessed by trained staff using the MDS for Home Care, 2.0 version. We argue that the harmonization by InterRAI of the MDS forms for different health settings, referred to as "the third generation of assessment," has produced the first scientific, standardized methodology in the approach to effective geriatric care.

Attenuation of Sarcopenia by Dietary Restriction in Rhesus Monkeys

Abstract: Sarcopenia, the loss of muscle mass with normal aging, devastates quality of life-and related healthcare expenditures are enormous. The prevention or attenuation of sarcopenia would be an important medical advance. Dietary restriction (DR) is the only dietary intervention that consistently extends median and maximum life span, as well as health span in rodents. Evidence suggests that DR will have a similar effect in primates. Furthermore, DR opposes sarcopenia in rodents. We tested the hypothesis that DR will reduce age-related sarcopenia in a nonhuman primate. Thirty adult male rhesus monkeys, half fed a normal calorie intake and half reduced by 30% in caloric intake, were examined over 17 years for changes in dual-energy X-ray absorptiometry-estimated skeletal muscle mass. Body weight-adjusted skeletal muscle mass declined somewhat in both groups but was far more rapid in the control group. We have shown that moderate, adult-onset DR can attenuate sarcopenia in a nonhuman primate model.

Executive Function and Gait in Older Adults With Cognitive Impairment

Abstract: Background. Cognitive impairment has been shown to predict falls risk in older adults. The ability to step accurately is necessary to safely traverse challenging terrain conditions such as uneven or slippery surfaces. However, it is unclear how well persons with cognitive impairment can step accurately to avoid such hazards and what specific aspects of cognition predict stepping ability in different patient populations. Methods. Healthy older adults (NC), patients with Mild Cognitive Impairment with only memory impairment (MCI-EF) or memory and executive function impairments (MCI+EF) and early Alzheimer's patients (AD) were timed as they performed a stepping accuracy test with increasing cognitive demand (Walking Trail-Making Test; W-TMT), which required stepping on instrumented targets with either increasing sequential numbers (W-TMT A) or alternating sequential numbers and letters (W-TMT B). Results. After accounting for age and baseline walking speed, the AD and MCI+EF groups were significantly slower than the NC and MCI-EF groups on the task with the highest cognitive demand, W-TMT B (interaction effect F = 6.781, p <.0001). No group differences were noted on the W-TMT A task that was less cognitively demanding. Neuropsychological measures of executive functioning were associated with slower W-TMT B performance, whereas memory, visual attention and visual spatial skills were not (adjusted R 2 = 0.42). Conclusions. Executive function is important for stepping performance, particularly under more complex environmental conditions.

Efficacy and Effectiveness of a Balance-Enhancing Insole

Abstract: Background. Age-related loss of foot-sole cutaneous sensation is very common and is associated with impaired balance control. This study investigated the effect of a balance-enhancing insole (designed to facilitate foot-sole sensation) on lateral gait stability and evaluated its effectiveness in daily life. Methods. Forty community-dwelling older adults (age 65‐75) with moderate loss of foot-sole sensation (unrelated to neuropathy) were fitted with the same model of walking shoes. Half of the participants were assigned, at random, to wear the shoes with a facilitatory insole for 12 weeks; the other participants wore a conventional insole. A gait perturbation protocol, simulating uneven terrain, was performed at baseline and after wearing the assigned insoles for 12 weeks. Participants were tested with both types of insoles during each gait-testing session and sent in weekly postcards with information pertaining to insole comfort, hours of wear, and falls. Results. The facilitatory insole improved lateral stability during gait, and this benefit did not habituate after 12 weeks of wearing the insole in daily life. Nine participants who wore conventional insoles experienced one or more falls, whereas only five of the facilitatory group fell. Although there were initial reports of mild discomfort in 10 cases, all but one participant tolerated the facilitatory insole, and most indicated that they would like to continue wearing the insole on a long-term basis. Conclusions. A relatively simple change in insole design can help to counter effects of age-related (non-neuropathic) decline in foot-sole sensitivity, and is a viable intervention to enhance balance control.

Sex Modifies the Relationship Between Age and Gait: A Population-Based Study of Older Adults

Abstract: Background. Adequate mobility is essential to maintain an independent and active lifestyle. The aim of this cross-sectional study is to examine the associations of age with temporal and spatial gait variables in a population-based sample of older people, and whether these associations are modified by sex. Methods. Men and women aged 60–86 years were randomly selected from the Southern Tasmanian electoral roll (n = 223). Gait speed, step length, cadence, step width, and double-support phase were recorded with a GAITRite walkway. Regression analysis was used to model the relationship between age, sex, and gait variables. Results. For men, after adjusting for height and weight, age was linearly associated with all gait variables (p <.05) except cadence (p =.11). For women, all variables demonstrated a curvilinear association, with age-related change in these variables commencing during the 7th decade. Significant interactions were found between age and sex for speed (p =.04), cadence (p =.01), and double-support phase (p =.03). Conclusion. Associations were observed between age and a broad range of temporal and spatial gait variables in this study. These associations differed by sex, suggesting that the aging process may affect gait in men and women differently. These results provide a basis for further research into sex differences and mechanisms underlying gait changes with advancing age.

Aging and Inflammation in Two Epidemiological Worlds

Abstract: Humans evolved in a world with high levels of infection resulting in high mortality across the life span and few survivors to advanced ages. Under such conditions, a strong acute-phase inflammatory response was required for survival; however, inflammatory responses can also promote chronic diseases of aging. We hypothesize that global historical increases in life span at older ages are partly explained by reduced lifetime exposure to infection and subsequent inflammation. To begin a test of this hypothesis, we compare C-reactive protein (CRP); levels in two populations with different epidemiological environments: the Tsimane of Bolivia and persons in the United States. High CRP is significantly more prevalent among the Tsimane up through middle age; by age 35, the Tsimane have spent more years with high CRP than have Americans at age 55. Further testing of the links among infection, inflammation, and chronic diseases of aging among the Tsimane requires collection of age-specific indicators of atherosclerosis and cardiac function.