Showing papers in "Journals of Gerontology Series A-biological Sciences and Medical Sciences in 2006"

The Loss of Skeletal Muscle Strength, Mass, and Quality in Older Adults: The Health, Aging and Body Composition Study

Abstract: BACKGROUND: The loss of muscle mass is considered to be a major determinant of strength loss in aging. However, large-scale longitudinal studies examining the association between the loss of mass and strength in older adults are lacking. METHODS: Three-year changes in muscle mass and strength were determined in 1880 older adults in the Health, Aging and Body Composition Study. Knee extensor strength was measured by isokinetic dynamometry. Whole body and appendicular lean and fat mass were assessed by dual-energy x-ray absorptiometry and computed tomography. RESULTS: Both men and women lost strength, with men losing almost twice as much strength as women. Blacks lost about 28% more strength than did whites. Annualized rates of leg strength decline (3.4% in white men, 4.1% in black men, 2.6% in white women, and 3.0% in black women) were about three times greater than the rates of loss of leg lean mass ( approximately 1% per year). The loss of lean mass, as well as higher baseline strength, lower baseline leg lean mass, and older age, was independently associated with strength decline in both men and women. However, gain of lean mass was not accompanied by strength maintenance or gain (ss coefficients; men, -0.48 +/- 4.61, p =.92, women, -1.68 +/- 3.57, p =.64). CONCLUSIONS: Although the loss of muscle mass is associated with the decline in strength in older adults, this strength decline is much more rapid than the concomitant loss of muscle mass, suggesting a decline in muscle quality. Moreover, maintaining or gaining muscle mass does not prevent aging-associated declines in muscle strength.

Aerobic Exercise Training Increases Brain Volume in Aging Humans

Abstract: Background The present study examined whether aerobic fitness training of older humans can increase brain volume in regions associated with age-related decline in both brain structure and cognition. Methods Fifty-nine healthy but sedentary community-dwelling volunteers, aged 60-79 years, participated in the 6-month randomized clinical trial. Half of the older adults served in the aerobic training group, the other half of the older adults participated in the toning and stretching control group. Twenty young adults served as controls for the magnetic resonance imaging (MRI), and did not participate in the exercise intervention. High spatial resolution estimates of gray and white matter volume, derived from 3D spoiled gradient recalled acquisition MRI images, were collected before and after the 6-month fitness intervention. Estimates of maximal oxygen uptake (VO2) were also obtained. Results Significant increases in brain volume, in both gray and white matter regions, were found as a function of fitness training for the older adults who participated in the aerobic fitness training but not for the older adults who participated in the stretching and toning (nonaerobic) control group. As predicted, no significant changes in either gray or white matter volume were detected for our younger participants. Conclusions These results suggest that cardiovascular fitness is associated with the sparing of brain tissue in aging humans. Furthermore, these results suggest a strong biological basis for the role of aerobic fitness in maintaining and enhancing central nervous system health and cognitive functioning in older adults.

Strength, But Not Muscle Mass, Is Associated With Mortality in the Health, Aging and Body Composition Study Cohort

Abstract: Background. Although muscle strength and mass are highly correlated, the relationship between direct measures of low muscle mass (sarcopenia) and strength in association with mortality has not been examined. Methods. Total mortality rates were examined in the Health, Aging and Body Composition (Health ABC) Study in 2292 participants (aged 70–79 years, 51.6% women, and 38.8% black). Knee extension strength was measured with isokinetic dynamometry, grip strength with isometric dynamometry. Thigh muscle area was measured by computed tomography (CT) scan, and leg and arm lean soft tissue mass were determined by dual energy x-ray absorptiometry (DXA). Both strength and muscle size were assessed as in gender-specific Cox proportional hazards models, with age, race, comorbidities, smoking status, level of physical activity, fat area by CT or fat mass by DXA, height, and markers of inflammation, including interleukin-6, C-reactive protein, and tumor necrosis factor-a considered as potential confounders. Results. There were 286 deaths over an average of 4.9 (standard deviation ¼ 0.9) years of follow-up. Both quadriceps and grip strength were strongly related to mortality. For quadriceps strength (per standard deviation of 38 Nm), the crude hazard ratio for men was 1.51 (95% confidence interval, 1.28–1.79) and 1.65 (95% confidence interval, 1.19–2.30) for women. Muscle size, determined by either CT area or DXA regional lean mass, was not strongly related to mortality. In the models of quadriceps strength and mortality, adjustment for muscle area or regional lean mass only slightly attenuated the associations. Further adjustment for other factors also had minimal effect on the association of quadriceps strength with mortality. Associations of grip strength with mortality were similar. Conclusion. Low muscle mass did not explain the strong association of strength with mortality, demonstrating that muscle strength as a marker of muscle quality is more important than quantity in estimating mortality risk. Grip strength provided risk estimates similar to those of quadriceps strength.

Phenotype of Frailty: Characterization in the Women's Health and Aging Studies

Abstract: Background "Frailty" is an adverse, primarily gerontologic, health condition regarded as frequent with aging and having severe consequences. Although clinicians claim that the extremes of frailty can be easily recognized, a standardized definition of frailty has proved elusive until recently. This article evaluates the cross-validity, criterion validity, and internal validity in the Women's Health and Aging Studies (WHAS) of a discrete measure of frailty recently validated in the Cardiovascular Health Study (CHS). Methods The frailty measure developed in CHS was delineated in the WHAS data sets. Using latent class analysis, we evaluated whether criteria composing the measure aggregate into a syndrome. We verified the criterion validity of the measure by testing whether participants defined as frail were more likely than others to develop adverse geriatric outcomes or to die. Results The distributions of frailty in the WHAS and CHS were comparable. In latent class analyses, the measures demonstrated strong internal validity vis a vis stated theory characterizing frailty as a medical syndrome. In proportional hazards models, frail women had a higher risk of developing activities of daily living (ADL) and/or instrumental ADL disability, institutionalization, and death, independently of multiple potentially confounding factors. Conclusions The findings of this study are consistent with the widely held theory that conceptualizes frailty as a syndrome. The frailty definition developed in the CHS is applicable across diverse population samples and identifies a profile of high risk of multiple adverse outcomes.

Effects of a physical activity intervention on measures of physical performance: Results of the lifestyle interventions and independence for Elders Pilot (LIFE-P) study.

Abstract: BACKGROUND: The Short Physical Performance Battery (SPPB), which includes walking, balance, and chair stands tests, independently predicts mobility disability and activities of daily living disability. To date, however, there is no definitive evidence from randomized controlled trials that SPPB scores can be improved. Our objective was to assess the effect of a comprehensive physical activity (PA) intervention on the SPPB and other physical performance measures. METHODS: A total of 424 sedentary persons at risk for disability (ages 70-89 years) were randomized to a moderate-intensity PA intervention or a successful aging (SA) health education intervention and were followed for an average of 1.2 years. RESULTS: The mean baseline SPPB score on a scale of 0-12, with 12 corresponding to highest performance, was 7.5. At 6 and 12 months, the PA versus SA group adjusted SPPB (+/- standard error) scores were 8.7 +/- 0.1 versus 8.0 +/- 0.1, and 8.5 +/- 0.1 versus 7.9 +/- 0.2, respectively (p < .001). The 400-meter walking speed was also significantly improved in the PA group. The PA group had a lower incidence of major mobility disability defined as incapacity to complete a 400-meter walk (hazard ratio = 0.71, 95% confidence interval = 0.44-1.20). CONCLUSIONS: A structured PA intervention improved the SPPB score and other measures of physical performance. An intervention that improves the SPPB performance may also offer benefit on more distal health outcomes, such as mobility disability.

Interleukin-6 in aging and chronic disease: a magnificent pathway.

Abstract: The human interleukin IL-6 was originally cloned in 1986. In 1993, William Ershler, in his article "IL-6: A Cytokine for Gerontologists," indicated IL-6 as one of the main signaling pathways modulating the complex relationship between aging and chronic morbidity. Over the last 12 years, our understanding of the role of IL-6 in human physiology and pathology has substantially grown, although some of the questions originally posed by Ershler are still debated. In this review, we will focus on IL-6 structure, IL-6 signaling, and trans signaling pathways, and the role of IL-6 in geriatric syndromes and chronic disease. In the final section of this review, we dissect the critical elements of the IL-6 signaling pathway and point out targets for intervention that are targeted by emerging drugs, some still on the horizon and others already being tested in clinical trials.

Low Nutrient Intake Is an Essential Component of Frailty in Older Persons

Abstract: Frailty is a syndrome associated with reduced functional reserve, impairment in multiple physiological systems, and reduced ability to regain physiological homeostasis after a stressful, destabilizing event. Frail older persons are at high risk of accelerated physical and cognitive functional decline, disability, and death (1–4). Identification of frailty in its early stage is important because interventions may, potentially, prevent or delay its clinical consequences. Recently, Fried and colleagues (2) defined frailty as a vicious cycle connecting specific signs and symptoms. Using data from the Cardiovascular Health Study, these authors developed and validated an operational definition of frailty as a clinical syndrome characterized by three or more of the following criteria: low muscle strength, unintentional weight loss, feeling of exhaustion, poor physical performance, and reduced physical activity. This definition of frailty was proposed and adopted at a recent American Geriatrics Society- and National Institute on Aging-sponsored national conference on the research agenda on frailty. In conceptualizing frailty, Fried and colleagues postulated that inadequate dietary intake is a component of the syndrome, which may trigger and/or sustain the cascade of the other processes that lead to frailty. Because nutritional data were not available in the Cardiovascular Health Study, weight loss was used as a proxy measure for inadequate dietary intake. However, because weight loss may be caused by diseases that increase catabolism (5), this measure may not be specific enough or sensitive to reduced energy and nutrient intakes. Additionally, when energy intake is adequate but the diet is deficient in certain nutrients, weight loss may not result. Muscle strength and exercise tolerance are at the core of the Fried and colleagues definition of frailty. Nutritional intake may affect muscle strength and exercise tolerance through a number of different mechanisms such as the proficiency of energy production in the aerobic metabolism, the regulation of muscle protein synthesis and/or breakdown, and scavenging of free radicals that may produce muscle damage and atrophy (6). The purpose of this study was to establish whether frailty as a syndrome and its components are associated with inadequate diet independent of major confounders. The InCHIANTI (Invecchiare in Chianti, aging in the Chianti area) study is particularly suited to address this gap in knowledge because it includes complete information on the Fried and colleagues frailty criteria as well as a detailed assessment of dietary intake. This study will help to refine the definition of frailty and, as a consequence, to improve the chances of its prevention and treatment.

Foot and Ankle Risk Factors for Falls in Older People: A Prospective Study

Abstract: BACKGROUND: Foot problems are common in older people and are associated with impaired balance and functional ability. Few prospective studies, however, have been undertaken to determine whether foot problems are a risk factor for falls. METHODS: One hundred seventy-six people (56 men and 120 women, mean age 80.1, standard deviation 6.4 years) residing in a retirement village underwent tests of foot and ankle characteristics (including foot posture, range of motion, strength, and deformity) and physiological falls risk factors (including vision, sensation, strength, reaction time, and balance) and were followed for 12 months to determine the incidence of falls. RESULTS: Seventy-one participants (41%) reported falling during the follow-up period. Compared to those who did not fall, fallers exhibited decreased ankle flexibility, more severe hallux valgus deformity, decreased plantar tactile sensitivity, and decreased toe plantarflexor strength; they were also more likely to have disabling foot pain. Discriminant function analysis revealed that decreased toe plantarflexor strength and disabling foot pain were significantly and independently associated with falls after accounting for physiological falls risk factors and age. CONCLUSIONS: Foot and ankle problems increase the risk of falls in older people. Interventions to address these factors may hold some promise as a falls prevention strategy. Language: en

Effects of Exercise on Mitochondrial Content and Function in Aging Human Skeletal Muscle

Abstract: Skeletal muscle mitochondria are implicated with age-related loss of function and insulin resistance. We examined the effects of exercise on skeletal muscle mitochondria in older (age=67.3±0.6 yr) men (n=5) and women (n=3). Similar increases in (P<0.01) cardiolipin (88.2±9.0 to 130.6±7.5 μg/mU creatine kinase activity (CK)) and the total mitochondrial DNA (1264±170 to 1895±273 copies per diploid of nuclear genome) reflected increased mitochondria content. Succinate oxidase activity, complexes 2–4 of the electron transport chain (ETC), increased from 0.13±0.02 to 0.20±0.02 U/mU CK (P<0.01). This improvement was more pronounced (P<0.05) in SS (127±48%) compared to IMF (56±12%) mitochondria. NADH oxidase activity, representing total ETC activity, increased from 0.51±0.09 to 1.00±0.09 U/mU CK (P<0.01). In conclusion, exercise enhances mitochondria ETC activity in older human skeletal muscle, particularly in SS mitochondria, which is likely related to the concomitant increases in mitochondria biogenesis.

Poor Sleep Is Associated With Impaired Cognitive Function in Older Women: The Study of Osteoporotic Fractures

Abstract: Background. The association between objectively measured sleep and cognition among community-dwelling elderly persons remains understudied. This observational, cross-sectional analysis examined this association. Methods. Results are from 2932 women (mean age 83.5 years) in the Study of Osteoporotic Fractures between 2002 and 2004. Cognitive function was measured by Mini-Mental State Examination (MMSE) and Trail Making B Test (Trails B). Cognitive impairment was definedas MMSE ,26 or Trails B .278 seconds. Sleep parameters measuredobjectively using actigraphy included total sleep time, sleep efficiency, sleep latency, wake after sleep onset (WASO), and total nap time. Results. There were 305 women (10.6%) with MMSE , 26 and 257 women (9.3%) with Trails B . 278 seconds. Compared with women with sleep efficiency � 70%, those with ,70% had a higher risk of cognitive impairment (MMSE , 26 multivariate odds ratio [MOR] ¼1.61; 95% confidence interval [CI], 1.20‐2.16; Trails B . 278 MOR ¼1.96; 95% CI, 1.43‐2.67). Higher sleep latency was associated with higher risk of cognitive impairment (per half hour: MMSE , 26 MOR ¼1.23; 95% CI, 1.13‐1.33; Trails B . 278 MOR ¼1.13; 95% CI, 1.04‐1.24), as was higher WASO (per half hour: MMSE , 26 MOR ¼1.15; 95% CI, 1.06‐1.23; Trails B . 278 MOR ¼1.24; 95% CI, 1.15‐1.34). Women who napped � 2 hours per day had a higher risk (MMSE , 26 MOR ¼1.42; 95% CI, 1.05‐1.93; Trails B . 278 MOR ¼1.74; 95% CI, 1.26‐2.40). There was no significant relationship for total sleep time. Conclusion. Objectively measured disturbed sleep was consistently related to poorer cognition, whereas total sleep time was not. This finding may suggest that it is disturbance of sleep rather than quantity that affects cognition.

Power Training Improves Balance in Healthy Older Adults

Abstract: Background. Age-related decline in muscle power may be an early indicator of balance deficits and fall risk, even in nonfrail adults. This study examined the dose-dependent effect of power training on balance performance in healthy older adults. Methods. One hundred twelve community-dwelling healthy older adults (69 6 6 years) were randomized to 8‐12 weeks of power training at 20% (LOW), 50% (MED), or 80% (HIGH) of maximal strength, or a nontraining control (CON) group. Participants trained twice weekly (five exercises; three sets of eight rapid concentric/slow eccentric repetitions) using pneumatic resistance machines. Balance, muscle performance (strength, power, endurance, contraction velocity), and body composition were measured. Results. Power training significantly improved balance performance (p ¼ .006) in participants who underwent power training compared to controls. Low intensity power training produced the greatest improvement in balance performance (p ¼ .048). Average contraction velocity at low load (40% one repetition maximum [1RM]) at baseline independently predicted improvement in balance following training (r ¼� .29, p ¼ .004). Conclusions. Power training improves balance, particularly using a low load, high velocity regimen, in older adults with initial lower muscle power and slower contraction. Further studies are warranted to define the mechanisms underlying this adaptation, as well as the optimum power training intensity for a range of physiological and clinical outcomes in older adults with varying levels of health status and functional independence.

A System of Integrated Care for Older Persons With Disabilities in Canada: Results From a Randomized Controlled Trial

Abstract: Background. Care for elderly persons with disabilities is usually characterized by fragmentation, often leading to more intrusive and expensive forms of care such as hospitalization and institutionalization. There has been increasing interest in the ability of integrated models to improve health, satisfaction, and service utilization outcomes. Methods. A program of integrated care for vulnerable community-dwelling elderly persons (SIPA [French acronym for System of Integrated Care for Older Persons]) was compared to usual care with a randomized control trial. SIPA offered community-based care with local agencies responsible for the full range and coordination of community and institutional (acute and long-term) health and social services. Primary outcomes were utilization and public costs of institutional and community care. Secondary outcomes included health status, satisfaction with care, caregiver burden, and out-of-pocket expenses. Results. Accessibility was increased for health and social home care with increased intensification of home health care. There was a 50% reduction in hospital alternate level inpatient stays (‘‘bed blockers’’) but no significant differences in utilization and costs of emergency department, hospital acute inpatient, and nursing home stays. For all study participants, average community costs per person were C$3390 higher in the SIPA group but institutional costs were C$3770 lower with, as hypothesized, no difference in total overall costs per person in the two groups. Satisfaction was increased for SIPA caregivers with no increase in caregiver burden or out-of-pocket costs. As expected, there was no difference in health outcomes. Conclusions. Integrated systems appear to be feasible and have the potential to reduce hospital and nursing home utilization without increasing costs.

Handgrip Strength and Cognitive Decline in Older Mexican Americans

Abstract: Background Cognitive decline and dementia are associated with disability and premature death in old age We examined whether low handgrip strength predicts subsequent cognitive decline in older Mexican Americans Methods We worked with a 7-year prospective cohort of 2160 noninstitutionalized Mexican Americans aged 65 years or older from the Hispanic Established Population for the Epidemiological Study of the Elderly (H-EPESE) who had a Mini-Mental State Examination (MMSE) score � 21 at baseline Measures included: (i) sociodemographic factors (age, gender, and education), handgrip strength, and near and distant visual impairment from baseline interview; and (ii) MMSE, body mass index (BMI), and medical conditions (stroke, heart attack, diabetes, depression, and hypertension) from four waves of data collection Results Using general linear mixed models, we found a significant trend with scores in the lowest quartile of handgrip strength at baseline to be associated with lower MMSE scores over time (estimate ¼� 128, standard error ¼ 016; p , 0001) There was a significant handgrip Strength-by-Time interaction with MMSE scores Participants in the lowest handgrip strength quartile had a greater cognitive decline over time (estimate ¼� 026, standard error ¼ 007; p , 001) than did those participants in the highest quartile This association remained statistically significant after controlling for potential confounding factors Conclusion Older Mexican Americans with reduced handgrip strength at baseline demonstrated a statistically significant decline in cognitive function over a 7-year period By contrast, participants in the highest handgrip strength quartile maintained a higher level of cognitive function

Anemia in Old Age Is Associated With Increased Mortality and Hospitalization

Abstract: Background. Anemia is common in old age and has been shown to affect older persons' physical function. To more fully understand the detrimental health effects of anemia, we examined the relationship of anemia with death and hospitalization outcomes in a large community-based sample of older persons. Methods. Data are from 3607 persons, aged 71 years or older, participating in the National Institute on Aging (NIA)-sponsored Established Populations for Epidemiologic Studies of the Elderly (EPESE) study. Anemia was defined according to World Health Organization (WHO) criteria as a hemoglobin concentration below 12 g/dL in women and below 13 g/dL in men. Data on subsequent mortality and hospital admissions over 4 years were obtained from death records and the Medicare database. Results. Anemia was present in 451 of the 3607 (12.5%) participants. During the follow-up period, anemic persons were more likely to die than were nonanemic persons (37.0% vs 22.1%, p < .001). Also, anemic persons were more often hospitalized (65.9% vs 54.6%, p < .001) and spent more days in hospital (25.0 vs 13.7, p < .001). After adjustment for demographics and baseline comorbidities, anemia significantly predicted subsequent mortality and hospitalization (relative risk = 1.61, 95% confidence interval, 1.34-1.93; and relative risk = 1.27, 95% confidence interval, 1.12-1.45, respectively). After excluding persons with prevalent diseases at baseline, anemia remained significantly associated with increased risks of mortality and hospitalization. A higher hemoglobin level was significantly associated with lower risks of mortality and hospitalization (p for trend < .001 for both). Conclusions. These findings indicate that late-life anemia characterizes persons at risk for important clinical health outcomes, and demonstrate the importance of clinical awareness of anemia even if the person is without apparent clinical disease.

The Influence of Age on the Effects of Lifestyle Modification and Metformin in Prevention of Diabetes

Abstract: Background The incidence of type 2 diabetes increases with age. It is unknown whether interventions to prevent diabetes are as effective in elderly persons as in younger adults.

Low Serum Micronutrient Concentrations Predict Frailty Among Older Women Living in the Community

Abstract: BACKGROUND Micronutrient deficiencies are common among older adults. We hypothesized that low serum micronutrient concentrations were predictive of frailty among older disabled women living in the community. METHODS We studied 766 women, aged 65 and older, from the Women's Health and Aging Study I, a population-based study of moderately to severely disabled community-dwelling women in Baltimore, Maryland. Serum vitamins A, D, E, B(6), and B(12), carotenoids, folate, zinc, and selenium were measured at baseline. Frailty status was determined at baseline and during annual visits for 3 years of follow-up. RESULTS At baseline, 250 women were frail and 516 women were not frail. Of 463 nonfrail women who had at least one follow-up visit, 205 (31.9%) became frail, with an overall incidence rate of 19.1 per 100 person-years. Compared with women in the upper three quartiles, women in the lowest quartile of serum carotenoids (hazard ratio [HR] 1.39; 95% confidence interval [CI], 1.01-1.92), alpha-tocopherol (HR 1.39; 95% CI, 1.02-1.92), and 25-hydroxyvitamin D (HR 1.34; 95% CI, 0.94-1.90) had an increased risk of becoming frail. The number of nutritional deficiencies (HR 1.10; 95% CI, 1.01-1.20) was associated with an increased risk of becoming frail, after adjusting for age, smoking status, and chronic pulmonary disease. Adjusting for potential confounders, we found that women in the lowest quartile of serum carotenoids had a higher risk of becoming frail (HR 1.54; 95% CI, 1.11-2.13). CONCLUSIONS Low serum micronutrient concentrations are an independent risk factor for frailty among disabled older women, and the risk of frailty increases with the number of micronutrient deficiencies.

One Year of Caloric Restriction in Humans: Feasibility and Effects on Body Composition and Abdominal Adipose Tissue

Abstract: Background. Caloric restriction (CR) increases maximal life span in short-lived organisms, and its effects are being explored in nonhuman primates. The objectives of this study were to determine the feasibility of prolonged CR in nonobese adults and to compare the effects of CR- and exercise-induced weight loss on body composition and abdominal adiposity. Methods. A randomized, controlled trial was conducted with 48 healthy, nonobese women and men, aged 57 6 1 (mean 6 standard error [SE]) years, with body mass index 27.3 6 0.3 kg/m 2 . Participants were randomly assigned to a 20% calorically-restricted diet (CR, n ¼ 19), exercise designed to produce a similar energy deficit (EX, n ¼ 19), or a healthy lifestyle control group (HL, n ¼ 10) for 1 year. Assessments included weight, body composition by dual-energy x-ray absorptiometry, abdominal adipose tissue by magnetic resonance imaging, and energy intake by doubly labeled water. Results. The average level of CR achieved by the CR group was 11.5 6 2.1%, and the EX group completed 59 6 6.7% of their prescribed exercise. Weight changes were greater (p � .0005) in the CR (� 8.0 6 0.9 kg) and EX (� 6.4 6 0.9) groups as compared to the HL group (� 1.3 6 0.9 kg), corresponding to reductions of 10.7%, 8.4%, and 1.7% of baseline weights, respectively. Whole-body fat mass and visceral and subcutaneous abdominal adipose tissue decreased significantly (p , .005) and comparably in the CR and EX groups, but did not change in the HL group. Conclusions. CR for 1 year was feasible, but the level of CR achieved was less than prescribed. CR and exercise were equally effective in reducing weight and adiposity.

Incidence and predictors of all and preventable adverse drug reactions in frail elderly persons after hospital stay.

Abstract: Background Adverse drug reactions (ADR) negatively impact life quality and are sometimes fatal. This study examines the incidence and predictors of all and preventable ADRs in frail elderly persons after hospital discharge, a highly vulnerable but rarely studied population. Methods The design was a prospective cohort study involving 808 frail elderly persons who were discharged from 11 Veteran Affairs hospitals to outpatient care. The main outcome measure was number of ADRs per patient as determined by blinded geriatrician and geropharmacist pairs using Naranjo's ADR algorithm. For all ADRs (possible, probable, or definite), preventability was assessed. Discordances were resolved by consensus conferences. Results Overall, 33% of patients had one or more ADRs for a rate of 1.92 per 1000 person-days of follow-up. The rate for preventable ADRs was 0.71 per 1000 person-days of follow-up. Independent risk factors for all ADRs were number of medications (adjusted [Adj.] hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.05-1.10 per medication), use of warfarin (Adj. HR, 1.51; 95% CI, 1.22-1.87), and (marginally) the use of benzodiazepines (Adj. HR, 1.23; 95% CI, 0.95-1.58). Counterintuitively, use of sedatives and/or hypnotics was inversely related to ADR risk (Adj. HR, 0.14; 95% CI, 0.04-0.57). Similar trends were seen for number of medications and warfarin use as predictors of preventable ADRs. Conclusions ADRs are very common in frail elderly persons after hospital stay, and polypharmacy and warfarin use consistently increase the risk of ADRs.

The ACTIVE Cognitive Training Trial and Health-Related Quality of Life: Protection That Lasts for 5 Years

Abstract: Objective. We evaluated the ability of the three cognitive training interventions (memory, reasoning, or speed of processing) fielded in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) multisite randomized controlled trial to protect against two thresholds of extensive decline in health-related quality of life (HRQoL) at 2 and 5 years post-training. Method. Adults aged 65 years or older (2802) were enrolled and randomized to three cognitive interventions or a nocontact control group. Data on 1804 participants were available at both the 2- and 5-year follow-ups. HRQoL was measured by the eight MOS 36-Item Short-Form Health Survey (SF-36) scales. Clinically relevant decline on each scale was defined as a drop of � 0.5 standard deviations from baseline. Extensive HRQoL decline was defined as clinically relevant drops on (i) � 4 SF-36 scales, and (ii) � 3 SF-36 scales, and was assessed using multiple logistic regressions, weighted to adjust for potential attrition bias. Results. At 2 years post-training, 23.7% and 36.6% had clinically relevant drops on � 4 and � 3 SF-36 scales, respectively. At 5 years post-training, 32.9% and 47.3% had clinically relevant drops on � 4 and � 3 SF-36 scales, respectively. Participants in the speed of processing intervention arm were significantly less likely to have extensive HRQoL decline compared to participants in the control group regardless of the threshold or time period, whereas participants in the memory and reasoning intervention arms were significantly less like to have extensive HRQoL decline only at 5 years post-training and only at the lower threshold. Conclusion. The effect of the speed of processing intervention was stronger and evident earlier than those for the memory and reasoning interventions. This result stems from the speed of processing intervention being the most procedural intervention, operating through sensory-motor elaboration and repetition, bringing about a broader pattern of regional brain activation. At 5 years post-training, however, all three interventions were successful in protecting against a lower threshold of age-related extensive declines in HRQoL.

Atrogin-1/MAFbx and MuRF1 Are Downregulated in Aging-Related Loss of Skeletal Muscle

Abstract: Muscle atrophy in many conditions share a common mechanism in the upregulation of the muscle-specific ubiquitin E3-ligases atrophy gene-1/muscle atrophy F-box (Atrogin-1/MAFbx) and muscle ring-finger protein 1 (MuRF1). E3-ligases are part of the ubiquitin proteasome pathway utilized for protein degradation during muscle atrophy. In this study, we provide new data to show that this is not the case in age-related loss of muscle mass (sarcopenia). On the contrary, Atrogin-1/MAFbx and MuRF1 are downregulated in skeletal muscle of 30-month-old rats, and our results suggest that AKT (protein kinase B)-mediated inactivation of forkhead box O 4 (FOXO4) underlies this suppression. The data also suggest that activation of AKT is mediated through the insulin-like growth factor-1 (IGF-1) receptor, signaling via ShcA-Grb2-GAB. Using dietary restriction, we find that it impedes sarcopenia as well as the effects of aging on AKT phosphorylation, FOXO4 phosphorylation, and Atrogin-1/MAFbx and MuRF1 transcript regulation. We conclude that sarcopenia is mechanistically different from acute atrophies induced by disuse, disease, and denervation.

Do Geriatric Interventions Reduce Emergency Department Visits? A Systematic Review

Abstract: Background Hospital emergency departments (EDs) serve an aging population with an increased burden on health resources. Few studies have examined the effects of comprehensive geriatric assessment interventions on ED use. This study aimed to systematically review the literature and compare the effects of these interventions on ED visits. Methods Relevant articles were identified through electronic databases and a search of reference lists and personal files. Inclusion criteria included: original research (written in English or French) on interventions conducted in noninstitutionalized populations 60 years old or older, not restricted to a particular medical condition, in which ED visits were a study outcome. Data were abstracted and checked by the first author and a research assistant using a standard protocol. Results Twenty-six relevant studies were identified, reported in 28 articles, with study samples obtained from EDs (9), hospitals (4), outpatient or primary care settings (10), home care (4), and community (1). The study designs included 17 randomized controlled trials, 3 trials with nonrandom allocation, 4 before-after studies, 1 quasi-experimental time-series study, and 1 cross-sectional study. Hospital-based interventions (mostly short-term assessment and/or liaison) had little overall effect on ED utilization, whereas many interventions in outpatient and/or primary care or home care settings (including geriatric assessment and management and case management) reduced ED utilization. Heterogeneity in study methods, measures of comorbidity, functional status, and ED utilization precluded meta-analysis of the results. Conclusion Further research, using improved methodologies and standardized measures, is needed to address the effects of innovative geriatric interventions on ED visits.

Physical activity status, but not age, influences inflammatory biomarkers and toll-like receptor 4.

Abstract: Background. Chronic inflammation has been implicated in the development of cardiovascular disease, diabetes mellitus, cachexia, and osteoporosis. Regular physical activity has been purported to possess ‘‘anti-inflammatory’’ properties which may limit chronic inflammation. Recently, we hypothesized that toll-like receptor 4 (TLR4) may play a role in activity-induced modulation of inflammation. Therefore, the purpose of this study was to determine the association between age, physical activity status, biomarkers of inflammation, and TLR4. Methods. Male and female participants (n ¼ 84) were recruited to fill one of the following groups: young (18‐30 years), active; young, inactive; old (60‐80 years), active; or old, inactive. To assess physical activity status, participants completed a Paffenbarger Physical Activity Questionnaire and a modified Balke submaximal treadmill test. After grouping and screening, participants were given a standard mixed diet to consume 24 hours prior to arriving at the laboratory. Participants were instructed to consume all food by 10 PM the night prior to blood sampling (8-hour fast). Following 30 minutes of seated rest in a quiet room, venous blood samples were collected. Lipopolysaccharide-stimulated inflammatory cytokine production and plasma high-sensitivity C-reactive protein (hsCRP) were determined by enzyme-linked immunosorbent assay, and TLR4 expression was determined by flow cytometry. Results. Lipopolysaccharide-stimulated interleukin-6, interleukin-1b, and tumor necrosis factor-a production, TLR4 expression, and hsCRP were significantly lower in active compared to inactive participants (p , .05). Also, older participants had significantly higher hsCRP than young participants had (p , .05). Conclusions. The findings of the present study support previous reports which infer that acute exercise or a physically active lifestyle may possess anti-inflammatory properties. Also this study, along with previous work from our laboratory, suggests that TLR4 may play a role in regulating the link between inflammatory cytokine production and a physically active lifestyle.

Functional Status of Centenarians in Tokyo, Japan: Developing Better Phenotypes of Exceptional Longevity

Abstract: Background. Centenarians are sometimes said to be representative of lifelong healthy aging. Whether they are, in fact, examples of healthy aging remains a subject of debate. The existence of heterogeneity in functional status has been reported repeatedly in previous studies of centenarians. However, there is as yet no standardized classification system with which to describe their functional phenotype. Methods. As part of a dynamic cohort study, we studied 304 centenarians (65 men and 239 women) living in Tokyo. Their functional status (sensory, physical, and cognitive), which we used to represent their phenotype, was assessed and subsequently classified by standard assessment methods (simple questionnaire, Barthel index, Mini-Mental State Examination, and the Clinical Dementia Rating, respectively). Results. We classified participants into 4 categories according to their functional status. Only 5 (2%) were classified as ‘‘Exceptional,’’ with all of their functions graded as excellent, and 56 (18%) were ‘‘Normal,’’ exhibiting maintenance of fine cognitive and physical functions. One hundred sixty-seven (55%) were ‘‘Frail,’’ exhibiting impairment of either cognitive or physical functions, and the remaining 76 (25%) were ‘‘Fragile,’’ exhibiting deterioration of both physical and cognitive functions. Conclusions. The relationships between biochemical marker, mortality rates, lifestyle, and functional phenotypes demonstrated by this classification method indicate that the system is reliable to address the functional status of extremely old persons. Thus, this framework would be a useful tool for exploring the factors that contribute to exceptional longevity as well as those that help to maintain the functional status of the extremely old population.

Effect of Alzheimer Caregiving Stress and Age on Frailty Markers Interleukin-6, C-Reactive Protein, and D-Dimer

Abstract: Background. Elevated plasma levels of interleukin (IL)-6, C-reactive protein (CRP), and D-dimer belong to the biological alterations of the ‘‘frailty syndrome,’’ defining increased vulnerability for diseases and mortality with aging. We hypothesized that, compatible with premature frailty, chronic stress and age are related in predicting inflammation and coagulation activity in Alzheimer caregivers. Methods. Plasma IL-6, CRP, and D-dimer levels were measured in 170 individuals (mean age 73 6 9 years; 116 caregivers, 54 noncaregiving controls). Demographic factors, diseases, drugs, and lifestyle variables potentially affecting inflammation and coagulation were obtained by history and adjusted for as covariates in statistical analyses. Results. Caregivers had higher mean levels of IL-6 (1.38 6 1.42 vs 1.00 6 0.92 pg/mL, p ¼ .032) and of D-dimer (723 6 530 vs 471 6 211 ng/mL, p , .001) than controls had. CRP levels were similar between groups (p ¼ .44). The relationship between caregiver status and D-dimer was independent of covariates (p ¼ .037) but affected by role overload. Age accounted for much of the relationship with IL-6. After controlling for covariates, the interaction between caregiver status and age was significant for D-dimer (b ¼ .20, p ¼ .029) and of borderline significance for IL-6 (b ¼ .17, p ¼ .090). Post hoc regression analyses indicated that, among caregivers, age was significantly correlated with both D-dimer (b ¼ .50, p , .001) and IL-6 (b ¼ .38, p ¼ .001). Among controls, however, no significant relationship was observed between age and either D-dimer or IL-6. Conclusions. The interaction between caregiving status and age for D-dimer and IL-6 suggests the possibility that older caregivers could be at risk of a more rapid transition to the frailty syndrome and clinical manifestations of cardiovascular diseases.

Childhood socioeconomic status predicts physical functioning a half century later

Abstract: Background. Socioeconomic status (SES) affects health outcomes at all stages of life. Relating childhood socioeconomic environment to midlife functional status provides a life course perspective on childhood factors associated with poor and good health status later in life. Methods. The British 1946 birth cohort was prospectively evaluated with periodic examinations from birth through age 53 years, when physical performance tests assessing strength, balance, and rising from a chair were administered. Early childhood socioeconomic factors were examined as predictors of low, middle, or high function at midlife. We tested the hypothesis that adulthood behavioral risk factors would explain the childhood SES–midlife physical function associations. Results. Multiple measures of childhood deprivation were associated with midlife function but in multivariate analyses only father’s occupation was associated with low function (relative risk [RR] for manual occupation ¼ 1.6; 95% confidence interval [CI], 1.1–2.3), and only mother’s education was associated with high function (RR for lower mother’s education ¼ 0.49; 95% CI, 0.34–0.72). Early adulthood behavioral risk factors and middle-age SES and disease status only modestly attenuated the relationship between father’s occupation and low function and had no impact on the relationship of mother’s education with high function. Conclusions. The social environment in which a child grows up has a strong association with midlife, objectively measured functional status, which is a reflection of the aging process and chronic diseases accumulated over the life course. Of particular interest is the role of higher maternal education in promoting high midlife functioning.

Pressure Ulcers Among Elderly Patients Early in the Hospital Stay

Abstract: Background. Pressure ulcers among elderly hospital patients diminish quality of life and increase the cost of hospital care. Evidence suggests that pressure ulcers can arise after only a few hours of immobility. The goals of this study were to estimate the incidence of hospital-acquired pressure ulcers in the first 2 days of the hospital stay and to identify patient characteristics associated with higher incidence. Methods. A prospective cohort study was performed between 1998 and 2001. A total of 3233 patients 65 years old or older admitted through the Emergency Department to the inpatient Medical Service at two study hospitals were examined by a research nurse on the third day of hospitalization. Pressure ulcers were ascertained using standard criteria and were classified as either preexisting, possibly hospital-acquired, or definitely hospital-acquired. Results. There were 201 patients with one or more possibly or definitely hospital-acquired pressure ulcers for a cumulative incidence of 6.2% (95% confidence interval, 5.4%‐7.1%). Most of the pressure ulcers were stage 2, and the majority were in the sacral area or on the heels. In multivariable analysis, pressure ulcer incidence was significantly associated with increasing age, male gender, dry skin, urinary and fecal incontinence, difficulty turning in bed, nursing home residence prior to admission, recent hospitalization, and poor nutritional status. Conclusions. A small but significant proportion of elderly emergently admitted hospital patients acquire pressure ulcers soon after their admission. New models of care may be required to ensure that preventive interventions are provided very early in the elderly person’s hospital stay.

daf-16 Protects the Nematode Caenorhabditis elegans During Food Deprivation

Abstract: Inhibition of either the insulin-like or target of rapamycin (TOR) pathways in the nematode Caenorhabditis elegans extends life span. Here, we demonstrate that starvation and inhibition of the C. elegans insulin receptor homolog (daf-2) elicits a daf-16-dependent up-regulation of a mitochondrial superoxide dismutase (sod-3). We also find that although heat and oxidative stress result in nuclear localization of the DAF-16 protein, these stressors do not activate a SOD-3 reporter, suggesting that nuclear localization alone may not be sufficient for transcriptional activation of DAF-16. We show that inhibition of either TOR activity or key components of the cognate translational machinery (eIF-4G and EIF-2B homologs) increases life span by both daf-16-dependent and -independent mechanisms. Finally, we demonstrate that at least one nematode hexokinase is localized to the mitochondria. We propose that the increased life spans conferred by alterations in both the TOR and insulin-like pathways function by inappropriately activating food-deprivation pathways.

Lower Plasma Vitamin E Levels Are Associated With the Frailty Syndrome: The InCHIANTI Study

Abstract: Background. The primary biologic mechanism that causes frailty in older persons has never been adequately explained. According to recent views, oxidative stress may be the driving force of this condition. We tested the hypothesis that, independent of confounders, low plasma levels of vitamin E (a-tocopherol), the main fat-soluble human antioxidant, are associated with the frailty syndrome in older persons free from dementia and disability. Methods. The study sample included 827 older (� 65 years) persons (women, 54%) who participated in a populationbased epidemiological study. Frail participants were identified based on the presence of at least three of five of the following features: self-reported weight loss, low energy, slow gait speed, low grip strength, and low physical activity. Participants with none of these features were considered nonfrail, while participants with one or two were considered intermediate frail. Plasma vitamin E levels were determined using reverse-phase high-performance liquid chromatography. Measured confounders included lower extremity muscle strength, cognitive function, diseases, and factors related to vitamin E metabolism. Results. Age- and gender-adjusted levels of vitamin E decreased gradually from the nonfrail to the frail group (p for trend ¼.015). In the logistic model adjusted for multiple potential confounders, participants in the highest vitamin E tertile were less likely to be frail than were participants in the lowest vitamin E tertile (odds ratio, 0.30; 95% confidence interval, 0.10‐0.91). Conclusions. Our findings show an association between low circulating levels of one of the most important components of the human antioxidant system and the presence of frailty.

Developmental Origins of Midlife Grip Strength: Findings From a Birth Cohort Study

Abstract: BACKGROUND: There is growing evidence that the prenatal environment has long-term effects on adult grip strength, but little is known about the effects of the postnatal environment. We tested whether prepubertal growth, pubertal growth, or the development of motor and cognitive capabilities was associated with midlife muscle strength independently of other determinants of grip strength. METHODS: Handgrip strength and body size were measured in a representative British sample of 1406 men and 1444 women 53 years old with prospective childhood data. Normal regression models were used to examine the effects of birth weight, postnatal height and weight gain before 7 years and between 7 and 15 years, motor milestones and cognitive ability on grip strength at age 53, taking account of lifetime social class, current physical activity, and health status. RESULTS: Birth weight and prepubertal height gain were associated with midlife grip strength, independently of later weight and height gain and other determinants. Pubertal growth was also independently associated with midlife grip strength; for men weight gain during puberty was beneficial, whereas for women it was height gain. Those participants with earlier infant motor development had better midlife grip strength, which was partly confounded by the growth trajectory. CONCLUSIONS: This study showed that components of prenatal, prepubertal, and pubertal growth have long-term effects on midlife grip strength. To the extent that these associations are modifiable, interventions in childhood that help to build muscle mass and strength, such as increased physical exercise, may have long-term beneficial effects on adult muscle strength and may help to prevent sarcopenia, disability, and frailty in later life

Vitamin and Carotenoid Status in Older Women: Associations With the Frailty Syndrome

Abstract: OBJECTIVE We investigated the relationship of micronutrient deficiencies with the frailty syndrome in older women living in the community. METHODS Frailty status and serum micronutrients were assessed in a cross-sectional study of 754 women, 70-80 years old, from the Women's Health and Aging Studies I and II. RESULTS Among nonfrail, prefrail, and frail women, respectively, geometric mean serum concentrations were 1.842, 1.593, and 1.376 micromol/L for total carotenoids (p <.001); 2.66, 2.51, and 2.43 micromol/L for retinol (p =.04); 50.9, 47.4, and 43.8 nmol/L for 25-hydroxyvitamin D (p =.019); 43.0, 35.8, and 30.9 nmol/L for vitamin B(6) (p =.002); and 10.2, 9.3, and 8.7 ng/mL for folate (p =.03). Frail women were more likely to have at least two or more micronutrient deficiencies (p =.05). The age-adjusted odds ratios of being frail were significantly higher for those participants whose micronutrient concentrations were in the lowest quartile compared to the top three quartiles for total carotenoids, alpha-tocopherol, 25-hydroxyvitamin D, and vitamin B(6). The association between nutrients and frailty was strongest for beta-carotene, lutein/zeaxanthin, and total carotenoids (odds ratio ranging from 1.82 to 2.45, p =.05), after adjusting for age, sociodemographic status, smoking status, and body mass index. CONCLUSION Frail women are more likely to have relatively low serum carotenoid and micronutrient concentrations and are more likely to have multiple micronutrient deficiencies. Future longitudinal studies are needed to examine the relationships between micronutrient concentrations and frailty in older women.