Showing papers in "Journals of Gerontology Series A-biological Sciences and Medical Sciences in 2007"
TL;DR: Although based on a simple count, the frailty index shows several interesting properties, including a characteristic rate of accumulation, a submaximal limit, and characteristic changes with age in its distribution.
Abstract: This review article summarizes how frailty can be considered in relation to deficit accumulation. Recalling that frailty is an age-associated, nonspecific vulnerability, we consider symptoms, signs, diseases, and disabilities as deficits, which are combined in a frailty index. An individual's frailty index score reflects the proportion of potential deficits present in that person, and indicates the likelihood that frailty is present. Although based on a simple count, the frailty index shows several interesting properties, including a characteristic rate of accumulation, a submaximal limit, and characteristic changes with age in its distribution. The frailty index, as a state variable, is able to quantitatively summarize vulnerability. Future studies include the application of network analyses and stochastic analytical techniques to the evaluation of the frailty index and the description of other state variables in relation to frailty.
1,998 citations
TL;DR: The 2006 Second International Working Meeting on Frailty and Aging as mentioned in this paper discussed the distinction between frailty and aging, its relationship with chronic disease, and the critical domains in its operational definition.
Abstract: Clinicians and researchers have shown increasing interest in frailty. Yet, there is still considerable uncertainty regarding the concept and its definition. In this article, we present perspectives on key issues and controversies discussed by scientists from 13 different countries, representing a diverse range of disciplines, at the 2006 Second International Working Meeting on Frailty and Aging. The following fundamental questions are discussed: What is the distinction, if any, between frailty and aging? What is its relationship with chronic disease? Is frailty a syndrome or a series of age-related impairments that predict adverse outcomes? What are the critical domains in its operational definition? Is frailty a useful concept? The implications of different models and approaches are examined. Although consensus has yet to be attained, work accomplished to date has opened exciting new horizons. The article concludes with suggested directions for future research.
1,030 citations
TL;DR: The phenotypic definition of frailty, which offers ready clinical operationalization, discriminates broad levels of risk but requires additional clinical translation, but allows the risk of adverse outcomes to be defined more precisely.
Abstract: Background. Many definitions of frailty exist, but few have been directly compared. We compared the relationship between a definition of frailty based on a specific phenotype with one based on an index of deficit accumulation. Methods. The data come from all 2305 people 70 years old and older who composed the clinical examination cohort of the second wave of the Canadian Study of Health and Aging. We tested convergent validity by correlating the measures with each other and with other health status measures, and analyzed cumulative index distributions in relation to phenotype. To test criterion validity, we evaluated survival (institutionalization and all-cause mortality) by frailty index (FI) score, stratified by the phenotypic definitions as ‘‘robust,’’ ‘‘pre-frail,’’ and ‘‘frail.’’ Results. The measures correlated moderately well with each other (R ¼ 0.65) and with measures of function (phenotypic definition R ¼0.66; FI R ¼0.73) but less well with cognition (phenotypic definition R ¼� 0.35; FI R ¼� 0.58). The median FI scores increased from 0.12 for the robust to 0.30 for the pre-frail and 0.44 for the frail. Survival was also lower with increasing frailty, and institutionalization was more common, but within each phenotypic class, there were marked differences in outcomes based on the FI values—e.g., among robust people, the median 5-year survival for those with lower FI values was 85%, compared with 55% for those with higher FI values. Conclusion. The phenotypic definition of frailty, which offers ready clinical operationalization, discriminates broad levels of risk. The FI requires additional clinical translation, but allows the risk of adverse outcomes to be defined more precisely.
1,007 citations
TL;DR: Frailty is an independent predictor of adverse health outcomes in older women, including very elderly women and older obese women.
Abstract: Methods. To determine whether a standard frailty phenotype was independently associated with risk of adverse health outcomes in older women and to evaluate the consistency of associations across risk subgroups defined by age and body mass index (BMI), we ascertained frailty status in a cohort of 6724 women � 69 years and followed them prospectively for incident falls, fractures, and mortality. Frailty was defined by the presence of three or more of the following criteria: unintentional weight loss, weakness, self-reported poor energy, slow walking speed, and low physical activity. Incident recurrent falls were defined as at least two falls during the subsequent year. Incident fractures (confirmed with x-ray reports), including hip fractures, and deaths were ascertained during an average of 9 years of follow-up. Results. After controlling for multiple confounders such as age, health status, medical conditions, functional status, depressive symptoms, cognitive function, and bone mineral density, frail women were subsequently at increased risk of recurrent falls (multivariate odds ratio ¼1.38, 95% confidence interval [CI], 1.02‐1.88), hip fracture (multivariate hazards ratio [MHR] ¼ 1.40, 95% CI, 1.03‐1.90), any nonspine fracture (MHR ¼ 1.25, 95% CI, 1.05‐1.49), and death (MHR ¼ 1.82, 95% CI, 1.56‐2.13). The associations between frailty and these outcomes persisted among women � 80 years. In addition, associations between frailty and an increased risk of falls, fracture, and mortality were consistently observed across categories of BMI, including BMI � 30 kg/m 2 .
617 citations
TL;DR: Central nervous system drugs, especially psychotropics, seem to be associated with an increased risk of falls.
Abstract: Background. Falls in older people are associated with poor prognosis. Medication use is a potential cause of falls. Our aim was to systemically review all original articles examining medication use as a risk factor for falls or fall-related fractures in people aged � 60 years. Methods. We searched English articles in Medline (1996–2004) indexed under ‘‘falls’’ or ‘‘accidental falls’’ and ‘‘pharmaceutical preparations’’ or specific groups of drugs. We excluded studies not meeting the age criterion, not controlled with nonusers of target medicines or nonfallers, or with no clear definition of target medication. Results. Twenty-eight observational studies and one randomized controlled trial met the inclusion criteria. The number of participants ranged from 70 to 132,873. The outcome measure was a fall in 22 studies and a fracture in 7 studies. The main group of drugs associated with an increased risk of falling was psychotropics: benzodiazepines, antidepressants, and antipsychotics. Antiepileptics and drugs that lower blood pressure were weakly associated with falls. Conclusions. Central nervous system drugs, especially psychotropics, seem to be associated with an increased risk of falls. The quality of observational studies needs to be improved, for many appear to lack even a clear definition of a fall, target medicines, or prospective follow-up. Many drugs commonly used by older persons are not systematically studied as risk factors for falls.
589 citations
TL;DR: Circulating indicators of AGEs (CML and MG derivatives), although elevated in older participants, correlate with indicators of inflammation and OS across all ages, and reduced consumption of these oxidants may prove a safe economic policy to prevent age-related diseases, especially in an aging population.
Abstract: Background—Oxidative stress (OS) and inflammatory mediators increase with aging. The levels of advanced glycation endproducts (AGEs), prooxidant factors linked to chronic diseases such as diabetes, cardiovascular disease, and renal disease, also increase with aging. AGEs are readily derived from heat-treated foods. We propose that the excess consumption of certain AGEs via the diet enhances OS and inflammatory responses in healthy adults, especially in elderly persons. Methods—We examined 172 young ( 60 years old) healthy individuals to determine whether the concentration of specific serum AGEs (N e -carboxymethyl-lysine [CML] or methylglyoxal [MG] derivatives) were higher in older compared to younger persons and whether, independent of age, they correlated with the intake of dietary AGEs, as well as with circulating markers of OS and inflammation. Results—Body weight, body mass index (BMI), and serum AGE, CML, and MG derivatives were higher in older participants, independent of gender. Serum CML correlated with levels of 8isoprostanes (r =0.448, p =.0001) as well as with Homeostasis Model Assessment index (HOMA), an index of insulin resistance (r = 0.247, p = .044). The consumption of dietary AGEs, but not of calories, correlated independently with circulating AGEs (CML: r =0.415, p = .0001 and MG: r = 0.282, p = .002) as well as with high sensitivity C-reactive protein (hsCRP) (r = 0.200, p = .042). Conclusions—Circulating indicators of AGEs (CML and MG derivatives), although elevated in older participants, correlate with indicators of inflammation and OS across all ages. Indicators of both AGEs and OS are directly influenced by the intake of dietary AGEs, independent of age or energy intake. Thus, reduced consumption of these oxidants may prove a safe economic policy to prevent age-related diseases, especially in an aging population.
466 citations
TL;DR: In this cohort, HIV infection was associated with an earlier occurrence of a phenotype that resembles the phenotype of frailty in older adults without HIV infection, and studies of frailt in the setting of HIV infection may help to clarify the biological mechanism ofFrailty.
Abstract: Background. Older healthy and HIV-infected adults exhibit physiological similarities. Frailty is a clinical syndrome associated with aging that identifies a subset of older adults at high risk of mortality and other outcomes. We investigated whether HIV infection increases the prevalence of a frailty-related phenotype (FRP) that approximates a clinical definition of frailty. Methods. We first defined the FRP and assessed its prevalence among HIV-uninfected men followed in the Multicenter AIDS Cohort Study (MACS) between 1994 and 2004. Using repeated measurements logistic regression models, we then assessed the association between FRP and HIV infection before the era of highly active antiretroviral therapies, adjusting for covariates among HIV-uninfected (N ¼ 1905) and incident HIV cases (N ¼ 245). Results. HIV infection was strongly associated with FRP prevalence. Compared to HIV-uninfected men of similar age, ethnicity and education, HIV-infected men were more likely to have the FRP for all durations of infection: for � 4 years, the adjusted odds ratio (OR) was 3.38, with 95% confidence interval (CI), 1.25‐9.11, and for 4.01‐8 years and 8.01‐12 years the corresponding figures were (OR ¼ 12.95, 95% CI, 6.60‐25.40) and (OR ¼ 14.68, 95% CI, 7.60‐28.35), respectively. The FRP prevalence for 55-year-old men infected with HIV for � 4 years (3.4%; 95% CI, 1.3‐8.6) was similar to that of uninfected men � 65 years old (3.4%; 95% CI, 1.5‐7.6). Conclusion. In this cohort, HIV infection was associated with an earlier occurrence of a phenotype that resembles the phenotype of frailty in older adults without HIV infection. Studies of frailty in the setting of HIV infection may help to clarify the biological mechanism of frailty.
378 citations
TL;DR: The association of ECF with gait speed decline is attenuated by comorbid conditions, particularly depression, and may point to new pathways for the treatment of physical decline associated with diminished cognitive function.
Abstract: BACKGROUND Emerging evidence indicates an association between cognitive function and physical performance in late life. This study examines the relationship between cognitive function and subsequent gait speed decline among high-functioning older adults. METHODS Measures of global cognitive function (Modified Mini Mental State Examination [3MS]) and executive control function (ECF) (a clock drawing task [CLOX 1] and the 15-item Executive Interview [EXIT 15]) were obtained in the Health, Aging, and Body Composition Study in 1999-2000. Gait-speed (meters/second) was assessed over 20 meters at usual pace. Using a mixed model, we assessed the relationship between baseline cognitive function and gait-speed change over 3 years. RESULTS Two thousand, three hundred forty-nine older adults (mean age 75.6 +/- 2.9 years) completed the assessments. After adjustment for baseline gait speed, a 1-standard-deviation (SD) lower performance on each cognitive test was associated with greater gait-speed decline over 3 years: 0.016 m/s for the 3MS (SD = 8.1), 0.009 m/s for CLOX 1 (SD = 2.4), and 0.012 m/s for EXIT 15 (SD = 4.1) (p <.0005 for all). After adjustment for comorbidities, the effect size was attenuated for 3MS and CLOX 1, and the association for EXIT 15 was no longer significant. Depression score was most strongly associated with the EXIT 15 effect reduction. CONCLUSION Global and executive cognitive functions predict declines in gait speed. The association of ECF with gait speed decline is attenuated by comorbid conditions, particularly depression. Elucidation of the mechanisms underlying these associations may point to new pathways for the treatment of physical decline associated with diminished cognitive function.
355 citations
TL;DR: Vitamin D status was inversely associated with poor physical performance and additional studies examining the association between vitamin D status and physical function are needed.
Abstract: With a growing older population, there is an increasing need to identify potentially modifiable risk factors for the onset of disability. In the past two decades, it has become evident that the role of vitamin D extends beyond calcium homeostasis and includes modulation of skeletal and cardiac muscle function, immune cell function, and anticancer activity (1). Within the muscle cell, vitamin D plays an important role in the regulation of calcium transport and protein synthesis (2,3). In older adults, low serum vitamin D (serum 25OHD) levels have been associated with muscle weakness, poor physical performance, balance problems, and falls, although findings from different studies are somewhat inconsistent (4–11). Thus, vitamin D deficiency may not only affect the onset of chronic conditions, which are frequent causes of disability, but may also directly affect functional status through vitamin D’s role in muscle function.
Consensus to define a cut-point for vitamin D insufficiency based on serum 25OHD levels is lacking. Various cut-points have been proposed based on population-based reference limits or biological indices, such as parathyroid hormone (PTH), calcium absorption, or bone mineral density, with cut-points for serum 25OHD insufficiency ranging from 50 to 80 nmol/L (12–14). Regardless, low levels of serum 25OHD are common in older populations with wide variability in prevalence depending on geographic location, season, and the cut-points used to define insufficiency and/or deficiency (15–19). Older adults are at risk for low serum 25OHD because of reduced exposure to ultraviolet B (UVB) radiation and reduced efficiency of previtamin D synthesis in the skin (20). Dietary intake of vitamin D is also often inadequate, as there are few natural food sources of vitamin D (16).
Low serum 25OHD may also indirectly affect muscle function via hyperparathyroidism secondary to vitamin D deficiency (17). Primary hyperparathyroidism is characterized by muscle weakness that is improved by treatment (21,22). It has been demonstrated that administration of PTH negatively affects skeletal muscle function in animal models (2,3,17). PTH has also been shown to induce the production of serum interleukin-6 (IL-6) (23). Observational studies have shown that elevated IL-6 levels are associated with lower muscle strength and poor physical performance (24,25). However, few studies have examined the joint effect of vitamin D and PTH on physical performance (9,10).
The objective of this study was to examine the associations between vitamin D status and physical performance using data from the InCHIANTI study. Comparisons between different serum 25OHD cut-points and physical performance were examined. Additionally, the association between PTH and physical performance and the role of PTH as a potential mediator in the association between serum 25OHD and physical performance was examined.
348 citations
TL;DR: Compared to women with no impairment, women with executive function impairment had significantly worse ADL and IADL function cross-sectionally and over 6 years, suggesting that screening of executive function can help to identify women at risk for functional decline and decreased survival.
Abstract: Background
Functional impairment in community-dwelling older adults is common and is associated with poor outcomes. Our goal was to compare the contribution of impairment in executive function or global cognitive function to predicting functional decline and mortality.
308 citations
TL;DR: It was found that only one diet was appropriate for DR experiments, indicating that much of the published work on fly "DR" may have included adverse effects of food composition.
Abstract: Dietary restriction (DR) extends life span in many organisms, through unknown mechanisms that may or may not be evolutionarily conserved. Because different laboratories use different diets and techniques for implementing DR, the outcomes may not be strictly comparable. This complicates intra- and interspecific comparisons of the mechanisms of DR and is therefore central to the use of model organisms to research this topic. Drosophila melanogaster is an important model for the study of DR, but the nutritional content of its diet is typically poorly defined. We have compared fly diets composed of different yeasts for their effect on life span and fecundity. We found that only one diet was appropriate for DR experiments, indicating that much of the published work on fly "DR" may have included adverse effects of food composition. We propose procedures to ensure that diets are suitable for the study of DR in Drosophila.
TL;DR: The results show that, after correcting for body mass and phylogeny, basal metabolic rate does not correlate with longevity in eutherians or birds, although it negatively correlates with marsupial longevity and time to maturity, and it is confirmed that age at maturity is typically proportional to adult life span.
Abstract: Comparative studies of aging are often difficult to interpret because of the different factors that tend to correlate with longevity. We used the AnAge database to study these factors, particularly metabolism and developmental schedules, previously associated with longevity in vertebrate species. Our results show that, after correcting for body mass and phylogeny, basal metabolic rate does not correlate with longevity in eutherians or birds, although it negatively correlates with marsupial longevity and time to maturity. We confirm the idea that age at maturity is typically proportional to adult life span, and show that mammals that live longer for their body size, such as bats and primates, also tend to have a longer developmental time for their body size. Lastly, postnatal growth rates were negatively correlated with adult life span in mammals but not in birds. Our work provides a detailed view of factors related to species longevity with implications for how comparative studies of aging are interpreted.
TL;DR: In this paper, the effects of 1-year whole-body vibration (WBV) training on isometric and explosive muscle strength and muscle mass in community-dwelling men older than 60 years were investigated.
Abstract: Background. This randomized controlled study investigated the effects of 1-year whole-body vibration (WBV) training on isometric and explosive muscle strength and muscle mass in community-dwelling men older than 60 years. Methods. Muscle characteristics of the WBV group (n ¼31, 67.3 6 0.7 years) were compared with those of a fitness (FIT) group (n ¼ 30, 67.4 6 0.8 years) and a control (CON) group (n ¼ 36, 68.6 6 0.9 years). Isometric strength of the knee extensors was measured using an isokinetic dynamometer, explosive muscle strength was assessed using a counter movement jump, and muscle mass of the upper leg was determined by computed tomography. Results. Isometric muscle strength, explosive muscle strength, and muscle mass increased significantly in the WBV group (9.8%, 10.9%, and 3.4%, respectively) and in the FIT group (13.1%, 9.8%, and 3.8%, respectively) with the training effectsnotsignificantlydifferentbetweenthegroups.NosignificantchangesinanyparameterwerefoundintheCONgroup. Conclusion. WBV training is as efficient as a fitness program to increase isometric and explosive knee extension strength and muscle mass of the upper leg in community-dwelling older men. These findings suggest that WBV training has potential to prevent or reverse the age-related loss in skeletal muscle mass, referred to as sarcopenia.
TL;DR: The findings support the use of individualized nonpharmacological interventions to treat agitation in persons with dementia and underscore the importance for clinicians of searching for underlying reasons for agitated behaviors.
Abstract: Objective. The objective of this study was to examine the efficacy of a systematic algorithm for providing individualized, nonpharmacological interventions for reducing agitated behaviors in nursing home residents with dementia. Methods. This placebo-controlled study combined nomothetic and ideographic methodologies. The study was conducted in 12 nursing home buildings in Maryland; 6 were used as treatment facilities, and 6 as control facilities. Participants were 167 elderly nursing home residents with dementia. Interventions were tailored to the individual profiles of agitated participants using a systematic algorithm that considered type of agitation and unmet needs. Interventions were then designed to fulfill the need in a manner that matched the person’s cognitive, physical, and sensory abilities, and their lifelong habits and roles. Interventions were provided for 10 days during the 4 hours of greatest agitation. Direct observations of agitation were recorded by trained research assistants via the Agitated Behavior Mapping Instrument (ABMI). Evaluation of positive and negative affect was also based on direct observation and assessed via Lawton’s Modified Behavior Stream. Data analysis was performed via SPSS software. Results. The implementation of personalized, nonpharmacological interventions resulted in statistically significant decreases in overall agitation in the intervention group relative to the control group from baseline to treatment (F1,164 ¼ 10.22, p ¼ .002). In addition, implementation of individualized interventions for agitation resulted in statistically significant increases in pleasure and interest (F1,164 ¼ 24.22, p , .001; F1,164 ¼ 20.66, p , .001). Conclusions. The findings support the use of individualized nonpharmacological interventions to treat agitation in persons with dementia and underscore the importance for clinicians of searching for underlying reasons for agitated behaviors.
TL;DR: Community occupational therapy should be advocated both for dementia patients and their caregivers, because it improves their mood, quality of life, and health status and caregivers' sense of control over life.
Abstract: Background. Cure of dementia is not possible, but quality of life of patients and caregivers can be improved. Our aim is to investigate effects of community occupational therapy on dementia patients’ and caregivers’ quality of life, mood, and health status and caregivers’ sense of control over life. Methods. Community-dwelling patients aged 65 years or older, with mild-to-moderate dementia, and their informal caregivers (n ¼ 135 couples of patients with their caregivers) were randomly assigned to 10 sessions of occupational therapy over 5 weeks or no intervention. Cognitive and behavioral interventions were used to train patients in the use of aids to compensate for cognitive decline and caregivers in coping behaviors and supervision. Outcomes, measured at baseline, 6 weeks, and 12 weeks, were patients’ and caregivers’ quality of life (Dementia Quality of Life Instrument, Dqol), patients’ mood (Cornell Scale for Depression, CSD), caregivers’ mood (Center for Epidemiologic Studies Depression Scale, CES-D), patients’ and caregivers’ health status (General Health Questionnaire, GHQ-12), and caregivers’ sense of control over life (Mastery Scale). Results. Improvement on patients’ Dqol overall (0.8; 95% confidence interval [CI], 0.6–.1, effect size 1.3) and caregivers’ Dqol overall (0.7; 95% CI, 0.5–.9, effect size 1.2) was significantly better in the intervention group as compared to controls. Scores on other outcome measures also improved significantly. This improvement was still significant at 12 weeks. Conclusion. Community occupational therapy should be advocated both for dementia patients and their caregivers, because it improves their mood, quality of life, and health status and caregivers’ sense of control over life. Effects were still present at follow-up.
TL;DR: Stance time variability is an independent predictor of future mobility disability and future efforts are needed to determine whether interventions that decrease stance time variability will also delay mobility disability.
Abstract: Background. Gait speed is a strong predictor of incident walking disability. The objective was to determine if gait variability adds to the prediction of incident mobility disability independent of gait speed. Methods. Participants included 379 older adults (mean age ¼ 79 years; 78% Caucasian, and 40% men) in the Cardiovascular Health Study at the Pittsburgh site. All could ambulate independently and reported no difficulty walking a half mile. Gait characteristics were determined from a 4-meter computerized walkway. For each gait parameter, variability was definedasthestandarddeviationfromtheindividualstepsfromtwopasses.Incidentwalkingdisabilitywasobtainedbyphone interviewevery6monthsfor54monthsand wasdefinedasnewdifficultywalkingahalfmileorinability towalkahalf mile. Results. Of the 379 participants, 222 (58.6%) developed incident mobility disability. In unadjusted Cox proportional hazards models gait speed, mean step length, mean stance time, and stance time variability were associated with incident mobility disability. After adjusting for gait speed, demographics, chronic conditions, prescription medications, health status, and physical activity level, only stance time variability remained an important indicator of disability. In the adjusted model, an increase in stance time variability of 0.01 seconds was associated with a 13% higher incidence of mobility disability (hazard ratio 1.13, 95% confidence interval, 1.01‐1.27). Conclusions. Stance time variability is an independent predictor of future mobility disability. Future efforts are needed to determine whether interventions that decrease stance time variability will also delay mobility disability.
TL;DR: In very healthy older adults, performance-based measures better predict early cognitive decline than do subjective measures, and tasks requiring greater functional reserve, such as fast-paced walking, appear to be the most sensitive in assessing these relationships.
Abstract: BACKGROUND: Recent evidence suggests that physical decline and slower gait may be associated with early signs of dementia, but more information on healthy older adults is needed. METHODS: We determined associations between cognitive function, gait speed, and self-reported measures of physical function in 3035 healthy mobile participants of the Ginkgo Evaluation of Memory Study evaluated in 2000-2001. Gait speed was measured over a 15-foot course with participants walking at both their usual and rapid pace. Self-reported difficulties with Activities of Daily Living (ADLs) and other physical function tasks were also collected. Results of the Modified Mini-Mental State Examination (3MSE) determined cognitive function. RESULTS: The average age of the cohort was 78.6 years (standard deviation [SD] 3.3), and 53.9% of participants were men. Mean gait speed was 0.95 (SD 0.23) m/s at a usual pace and 1.35 (SD 0.58) m/s at a rapid pace. More than three-fourths of participants had 3MSE scores > 90. In multiple logistic models adjusted for demographics and comorbidities, risk of low cognition (defined as 3MSE score of 80-85) was almost twice as great for participants in the slowest quartile of the rapid-paced walking task than for the fastest walkers (odds ratio: 1.96, 95% confidence interval, 1.25-3.08). Associations between cognition and usual-paced walking were borderline, and no relationships were found with self-reported measures of physical function, including ADLs. CONCLUSIONS: In very healthy older adults, performance-based measures better predict early cognitive decline than do subjective measures, and tasks requiring greater functional reserve, such as fast-paced walking, appear to be the most sensitive in assessing these relationships. Language: en
TL;DR: Serum CRP and cytokines increased drastically in postop hip-fracture elderly patients, whereas cytokines significantly increased only in IMS patients, raising questions about possible effects that cytokine generation, after hip- fracture repair, might have on cognition and complications.
Abstract: BACKGROUND The study aim was to determine the kinetics of serum pro- and anti-inflammatory cytokines and C-reactive protein (CRP) in hip-fracture patients over a month postfracture, and their relationship to postoperative (postop) complications and cognitive level. METHODS Forty-one elderly hip-fracture patients were prospectively followed. Serum was obtained during the first 10 hours postfracture and presurgery, 48-60 hours postop, 7 and 30 days postop, measuring CRP, interleukin-1beta (IL-1beta), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), IL-10, and IL-1 receptor antagonist (IL-1RA). RESULTS A significant increase was found postop for CRP, IL-6, TNF-alpha, IL-1RA (p <.001), IL-10 (p <.002), and IL-8 (p =.05). CRP kinetics curves were higher in patients with complications as a group, and in those suffering from infections, delirium, and cardiovascular complications (p <.05). IL-6 increase in patients with complications approached significance. Additional complications appeared in patients with impaired mental status (IMS) versus cognitively normal patients (p =.037). Higher kinetics curves in the IMS patients were found for CRP and IL-6 (p <.05). Analyzing the interaction effect of complications and IMS on CRP and cytokines production demonstrated that the increase in CRP was independently related to complications and IMS. IL-6, IL-8, and IL-10 were higher in IMS patients but not in patients with complications without IMS (p <.05). CONCLUSIONS Serum CRP and cytokines increased drastically in postop hip-fracture elderly patients. Only CRP significantly and independently increased in IMS patients and in patients with complications, whereas cytokines significantly increased only in IMS patients. This study raises questions about possible effects that cytokine generation, after hip-fracture repair, might have on cognition and complications.
TL;DR: Investment in aging research has been greater in the United States than the United Kingdom, particularly in population studies investigating healthy aging or frailty and their determinants, or cohort changes in health and functioning, but this is beginning to change.
Abstract: OVER the last 25 years, investment in aging research has been greater in the United States than the United Kingdom, particularly in population studies investigating healthy aging or frailty and their determinants, or cohort changes in health and functioning. It is still unclear, in the U.K. context, whether age-related declines in health and functioning of cohorts now in late middle age will differ from that of current older people, and whether socioeconomic and gender differences in aging and expectations of life at older ages are changing. In 2005, a House of Lords scientific report on aging (1) called for new research to address these questions with a focus on the underlying lifetime process of biological aging that could integrate the rather separate research on specific age-related diseases, and translate evidence into policy and practice. Investment in U.K. aging research is beginning to change. Healthy aging has become a preoccupation of the British government. For example, the U.K. Treasury, as part of the 2007 Spending Review, highlighted aging as one of the Grand Challenges faced by the U.K.; it is concerned with the economic and social consequences of the rapid increase in the old age dependency ratio as the baby boom generation reaches retirement age (2). There are calls for a step change in multidisciplinary research to understand healthy aging and how to maintain a population that remains healthy and productive longer (3). Policymakers recognize that healthy, independent, and active aging not only enhances individual lives but also addresses the social and economic implications of an aging population, and relieves pressure on public spending (4). U.K. research councils are making available new funding streams for aging initiatives, often spanning several councils, to address these concerns. The New Dynamics of Ageing research program (5) and the recent call for Medical Research Council Centres for Lifelong Health and Wellbeing (6) epitomize the growing interest in multidisciplinarity, life course approaches to aging, and expectations for knowledge transfer and user engagement. These calls for research highlight the consensus that the aging process operates from the beginning of life, driven by the rate of accumulation of molecular and cellular damage. Growing evidence from life course and historical cohort studies that adult function and age-related chronic diseases have their origins in early life experience and share common risk factors and causative mechanisms support this consensus (7,8). Modifiable factors such as nutrition and activity and chance events acting across the life course can alter exposure to sources of damage and the effectiveness of body systems for maintenance and repair (9). While genes have traditionally been seen as a nonmodifiable factor, there is growing evidence linking epigenetic DNA modification through environmental exposures to a wide range of aging phenotypes. This focus on early life and life course determinants of aging is stronger in the U.K. than the U.S. It partly arises from greater opportunities in the U.K. to capitalize on the maturing birth cohort studies and the historical cohort studies that have imaginatively linked development and early environment to later health outcomes (10,11). Investigators of maturing birth cohort and aging cohort studies increasingly share a common interest in characterizing aging trajectories and the extent of variation between individuals and across gender or social groups. They are interested in how dynamic relationships between different aging trajectories unfold over time and the common mechanisms or sources of risk, and in relating aging trajectories and their determinants to disease incidence, quality of life, and survival. The advantage of birth cohort studies is that they permit exploration of how biological, psychological, and social risk factors or risk factor trajectories, acting independently, cumulatively, or interactively across the whole life course, influence aging trajectories. This growing focus on life course determinants of aging has implications for studies of capability, the mechanisms of biological aging, and the clinical syndrome of frailty.
TL;DR: Gait changes following a physical fatiguing task agree with changes previously found in older persons at risk of falling, suggesting that physical fatigue may represent a risk factor for falls in elderly persons.
Abstract: Background. Fatigue affects self-reported functioning in older persons. Balance and gait problems increase fall risk. The effect of physical fatigue in the elderly population in general, and on balance control during walking in particular is not well known. This study investigates how a repeated sit-to-stand task affects gait control in older persons. Methods. Twenty-two persons (mean age 78 years) took part in a fatigue group (FG), and 22 persons (mean age 80 years) in a matched control group (CG). Participants walked back and forth on a walkway at different walking speeds. Gait data were adjusted for pretest–posttest differences in walking speed. The FG participants were physically fatigued by a repeated sit-to-stand task. Trunk data were obtained by a triaxial accelerometer and foot level data by an electronic walkway. Results. There were no group differences in preferred gait speed (p ¼ .96) or in step length (p ¼ .47) following the fatiguing task, but there were significant increases in step width (p ¼ .023) and in mediolateral trunk acceleration amplitude (p ¼ .038) in the FG group. Step-length variability (p ¼ .004) and interstride trunk acceleration variability in the vertical direction (p ¼ .002) increased, and tended to increase in the anteroposterior direction (p ¼ .10) and to decrease in the mediolateral direction (p ¼ .10) in the FG only. Conclusion. Gait changes following a physical fatiguing task agree with changes previously found in older persons at risk of falling, suggesting that physical fatigue may represent a risk factor for falls in elderly persons.
TL;DR: The data indicate that lifelong reduction in Gpx4 increased life span and reduced/retarded age-related pathology most likely through alterations in sensitivity of tissues to apoptosis.
Abstract: Glutathione peroxidase 4 (Gpx4) is an antioxidant defense enzyme that plays an important role in detoxification of oxidative damage to membrane lipids. Because oxidative stress is proposed to play a causal role in aging, we compared the life spans of Gpx4 heterozygous knockout mice (Gpx4 +/- mice) and wild-type mice (WT mice). To our surprise, the median life span of Gpx4 4/- mice (1029 days) was significantly longer than that of WT mice (963 days) even though the expression of Gpx4 was reduced approximately 50% in all tissues of Gpx4 +/- mice. Pathological analysis revealed that Gpx4 +/- mice showed a delayed occurrence of fatal tumor lymphoma and a reduced severity of glomerulonephritis. Compared to WT mice, Gpx4 +/- mice showed significantly increased sensitivity to oxidative stress-induced apoptosis. Our data indicate that lifelong reduction in Gpx4 increased life span and reduced/retarded age-related pathology most likely through alterations in sensitivity of tissues to apoptosis.
TL;DR: Measurements indicate that age-induced mtDNA deletion mutations expand within individual muscle fibers, eliciting fiber dysfunction and breakage.
Abstract: Although mitochondrial mutation abundance has been recognized to increase in an age-dependent manner, the impact of mutation has been more difficult to establish. Using quantitative polymerase chain reaction, we measured the intracellular abundance of mutant and wild-type mitochondrial genomes along the length of individual laser-captured microdissected muscle fibers from aged rat quadriceps. Aged muscle fibers possessed segmental, clonal intracellular expansions of unique somatically derived mitochondrial DNA (mtDNA) deletion mutations. When the mutation abundance surpassed 90% of the total mitochondrial genomes, the fiber lost cytochrome c oxidase activity and exhibited an increase in succinate dehydrogenase activity. In addition to the mitochondrial enzymatic abnormalities, some fibers displayed abnormal morphology such as fiber splitting, atrophy, and breakage. Deletion mutation accumulation was linked to these aberrant morphologies with more severe cellular pathologies resulting from higher deletion mutation abundance. In summary, our measurements indicate that age-induced mtDNA deletion mutations expand within individual muscle fibers, eliciting fiber dysfunction and breakage.
TL;DR: A community-based multifaceted intervention was effective in improving balance, mobility, and leg strength, all known fall risk factors in community-living older adults.
Abstract: Objective The purpose of this study was to evaluate the effectiveness of a 12-month community-based intervention on falls and risk factors (balance, lower extremity strength, and mobility) in community-living older adults. Methods Four hundred fifty-three sedentary adults (65 years old or older) were randomized to either a multifaceted intervention (3 times a week group exercise, 6 hours of fall prevention education, comprehensive falls risk assessment results sent to primary health care provider) or control group (written materials on falls prevention). Primary outcome was fall incidence rates calculated from self-reported falls reported monthly for 12 months. Secondary outcomes were tests of leg strength, balance, and mobility prior to and following the 12-month intervention. Results Twelve-month follow-up was completed on 95% of participants. Intent-to-treat analysis found that the incidence rate of falls was 25% lower among those in the intervention group compared with control group (1.33 vs 1.77 falls/person-year, rate ratio 0.75, 95% confidence interval [CI], 0.52-1.09). This difference was not statistically significant. The risk ratio for any fall was 0.96 (95% CI, 0.82-1.13). Small but significant improvements were found on the Berg Balance Test (adjusted mean difference +1.5 points, 95% CI, 0.8-2.3), the Chair Stand Test (adjusted mean difference +1.2, 95% 0.6-1.9), and the Timed Up and Go Test (adjusted mean difference -0.7, 95% CI, -1.2 to -0.2). Conclusions A community-based multifaceted intervention was effective in improving balance, mobility, and leg strength, all known fall risk factors. Although the incidence of falls was lower, the confidence interval included the possibility of no intervention effect on falls.
TL;DR: This report summarizes Task Force discussions held in Bethesda, Maryland and serves as an introduction to the following three articles that address specific issues such as the nosological classification of impairment for the construction of comorbidity measures, staging and classification of disease severity, and methodological and analytical issues.
Abstract: The National Institute on Aging (NIA) Geriatrics and Clinical Gerontology (GCG) Program convened an interdisciplinary Task Force on Comorbidity to foster the development of a research agenda on the multiple concurrent health problems that often occur in older persons. This report summarizes Task Force discussions held in Bethesda, Maryland (October 21–22, 2003; July 20–21, 2004) and serves as an introduction to the following three articles that address specific issues such as the nosological classification of impairment for the construction of comorbidity measures, staging and classification of disease severity, and methodological and analytical issues.
The risk of developing concomitant chronic illnesses and physiological limitations escalates with aging. Diabetes, respiratory diseases, cancer, cardiovascular problems, arthritis, hypertension, and certain other chronic conditions are more common in older than in younger persons. As a consequence, a new diagnosis of any common chronic health condition is likely to be made in the context of preexisting health problems.
TL;DR: More disability-free years were gained than total life years in persons free of stroke, cognitive impairment, arthritis, and/or visual impairment at baseline, suggesting that elimination of these conditions would result in a compression of disability.
Abstract: Background. The consequences of diseases in later life have been judged predominantly through mortality, resulting in an emphasis on the fatal rather than the nonfatal disabling conditions. We use a longitudinal study with follow-up at 2, 6, and 10 years to assess the impact of different diseases on both total life expectancy (TLE) and disability-free life expectancy (DFLE). Methods. The Medical Research Council Cognitive Function and Ageing Study investigators interviewed 13,004 people aged 65 years and older from five U.K. centers starting in 1991. Persons aged 75 years and older were oversampled. Disability (mild, moderate, and severe) was assessed through basic Activities of Daily Living (ADL) and Instrumental ADL (IADL) scales at baseline and at follow-ups at 2, 6, and 10 years. TLE and DFLE were compared for persons with and without each of nine conditions. Results. At age 65, men had a TLE of 15.3 years of which 12.1 (79%) were free of any disability, whereas women of the same age had an average TLE of 19.4 years, 11.0 years (57%) disability-free. Men (women) aged 65 years without
TL;DR: Smaller gray matter volumes in regions crucial for motor control are associated with slower gait and poorer balance, and the association appears to be independent of other diffuse brain abnormalities such as white matter hyperintensities.
Abstract: Background. In community-dwelling older adults, greater mobility impairment is associated with greater burden of diffuse brain structural abnormalities, such as higher white matter hyperintensities. This study examined the association between gray matter volumes of regions related to motor control, gait, and balance and whether this association is independent of burden of white matter hyperintensities. Methods. A random sample of 327 participants of the Cardiovascular Health Study (78.3 6 4.1 years old, 57% women) contributed brain magnetic resonance imaging (MRI) and mobility data. A brain imaging automated method measured gray matter volume in cerebellum, basal ganglia, and prefrontal and parietal cortex in both hemispheres. Gait speed was measured while walking 15 feet at usual pace. Standing balance was assessed by timing tandem stance. Associations between each region’s volume and gait speed or balance were measured before and after adjustment for demographics, head size, cardiovascular risk factors, and 0–9 grading scores of white matter hyperintensities. Results. Smaller left cerebellum and left prefrontal regions were associated with slower gait, independently of covariates and of white matter hyperintensities. Smaller right putamen, right posterior superior parietal cortex, and both left and right cerebellum were associated with balance difficulty, independently of covariates and white matter hyperintensities. Conclusions. Smaller gray matter volumes in regions crucial for motor control are associated with slower gait and poorer balance, and the association appears to be independent of other diffuse brain abnormalities such as white matter hyperintensities.
TL;DR: Heterogeneity between studies indicates that the Morse Falls Scale and STRATIFY may still be useful in particular settings, but that widespread adoption of either is unlikely to generate benefits significantly greater than that of nursing staff clinical judgment.
Abstract: Introduction. Fall risk screening tools are frequently used as a part of falls prevention programs in hospitals. Design-related bias in evaluations of tool predictive accuracy could lead to overoptimistic results, which would then contribute to program failure in practice. Methods. A systematic review was undertaken. Two blind reviewers assessed the methodology of relevant publications into a four-point classification system adapted from multiple sources. The association between study design classification and reported results was examined using linear regression with clustering based on screening tool and robust variance estimates with point estimates of Youden Index (= sensitivity + specificity - 1) as the dependent variable. Meta-analysis was then performed pooling data from prospective studies. Results. Thirty-five publications met inclusion criteria, containing 51 evaluations of fall risk screening tools. Twenty evaluations were classified as retrospective validation evaluations, 11 as prospective (temporal) validation evaluations, and 20 as prospective (external) validation evaluations. Retrospective evaluations had significantly higher Youden Indices (point estimate [95% confidence interval]: 0.22 [0.11, 0.33]). Pooled Youden Indices from prospective evaluations demonstrated the STRATIFY, Morse Falls Scale, and nursing staff clinical judgment to have comparable accuracy. Discussion. Practitioners should exercise caution in comparing validity of fall risk assessment tools where the evaluation has been limited to retrospective classifications of methodology. Heterogeneity between studies indicates that the Morse Falls Scale and STRATIFY may still be useful in particular settings, but that widespread adoption of either is unlikely to generate benefits significantly greater than that of nursing staff clinical judgment. Copyright 2007 by The Gerontological Society of America.
TL;DR: Data show that the regulation of ubiquitin proteasome-related genes involved with muscle atrophy are altered in very old women (>80 years).
Abstract: Background. Skeletal muscle atrophy in rodents is associated with increased gene expression of proteolytic markers muscle-RING-finger protein 1 (MuRF-1) and atrogin-1. In humans with age-related muscle atrophy, known as sarcopenia, little is known about these key proteolytic biomarkers. Therefore, the purpose of this investigation was 2-fold: (i) measure messenger RNA (mRNA) expression of proteolytic genes MuRF-1, atrogin-1, forkhead box (FOXO)3A, and tumor necrosis factor-a (TNF-a) in young and old women at rest, and (ii) measure these proteolytic genes in response to an acute resistance exercise (RE) bout, a known hypertrophic stimulus. Methods. A group of old women (OW: n ¼ 6, 85 6 1 years, thigh muscle ¼ 89 6 4c m 2 ) and young women (YW: n ¼ 8, 23 6 2 years, thigh muscle ¼ 122 6 6c m 2 ) performed three sets of 10 knee extensions at 70% of one-repetition maximum. Muscle biopsies were taken from the vastus lateralis before and 4 hours after RE. Using real-time reverse transcription‐polymerase chain reaction (RT‐PCR), mRNA was amplified and normalized to GAPDH. Results. At rest, OW expressed higher mRNA levels of MuRF-1 ( p ¼ .04) and FOXO3A ( p ¼ .001) compared to YW. In response to RE, there was an age effect ( p ¼ .01) in the induction of atrogin-1 (OW: 2.5-fold). Both YW and OW had an induction ( p ¼ .001) in MuRF-1 (YW: 3.6-fold; OW: 2.6-fold) with RE. Conclusions. These data show that the regulation of ubiquitin proteasome-related genes involved with muscle atrophy are altered in very old women (. 80 years). This finding is manifested both at rest and in response to RE, which may contribute to the large degree of muscle loss with age.
TL;DR: Involving older patients in setting chronic disease goals and decision-making appears to be especially important for self-care areas that demand more behaviorally complex lifestyle adjustments such as exercise, diet, and blood glucose monitoring.
Abstract: Background. Effective chronic disease self-management among older adults is crucial for improved clinical outcomes. We assessed the relative importance of two dimensions of physician communication-provision of information (PCOM) and participatory decision-making (PDM)-for older patients' diabetes self-management and glycemic control. Methods. We conducted a national cross-sectional survey among 1588 older community-dwelling adults with diabetes (response rate: 81%). Independent associations were examined between patients' ratings of their physician's PCOM and PDM with patients' reported diabetes self-management (medication adherence, diet, exercise, blood glucose monitoring, and foot care), adjusting for patient sociodemographics, illness severity, and comorbidities. Among respondents for whom hemoglobin A1c (HbAlc) values were available (n = 1233), the relationship was assessed between patient self-management and HbAlc values. Results. In separate multivariate regressions, PCOM and PDM were each associated with overall diabetes self-management (p <.001) and with all self-management domains (p <.001 in all models), with the exception of PDM not being associated with medication adherence. In models with both PCOM and PDM, PCOM alone predicted medication adherence (p -.001) and foot care (p -.002). PDM alone was associated with exercise and blood glucose monitoring (both p <.001) and was a stronger independent predictor than PCOM of diet. Better patient ratings of their diabetes self-management were associated with lower HbAlc values (B = -.10, p =.005). Conclusion. Among these older adults, both their diabetes providers' provision of information and efforts to actively involve them in treatment decision-making were associated with better overall diabetes self-management. Involving older patients in setting chronic disease goals and decision-making, however, appears to be especially important for self-care areas that demand more behaviorally complex lifestyle adjustments such as exercise, diet, and blood glucose monitoring.
TL;DR: The results indicate that the ACTN3 R577X polymorphism influences the response of quadriceps muscle power to ST in older adults.
Abstract: Background. The alpha-actinin-3 (ACTN3) R577X polymorphism has been associated with muscle power performance in cross-sectional studies. Methods. We examined baseline knee extensor concentric peak power (PP) and PP change with ;10 weeks of unilateral knee extensor strength training (ST) using air-powered resistance machines in 71 older men (65 [standard deviation ¼ 8] years) and 86 older women (64 [standard deviation ¼ 9] years). Results. At baseline in women, the XX genotype group had an absolute (same resistance) PP that was higher than the RR (p ¼ .005) and RX genotype groups (p ¼ .02). The women XX group also had a relative (70% of one-repetition maximum [1-RM]) PP that was higher than that in the RR (p ¼.002) and RX groups (p ¼.008). No differences in baseline absolute or relative PP were observed between ACTN3 genotype groups in men. In men, absolute PP change with ST in the RR (n ¼16) group approached a significantly higher value than in the XX group (n ¼9; p ¼.07). In women, relative PP change with ST in the RR group (n ¼ 16) was higher than in the XX group (n ¼ 17; p ¼ .02). Conclusions. The results indicate that the ACTN3 R577X polymorphism influences the response of quadriceps muscle power to ST in older adults.