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Background. Short-term adherence to physical activity (PA) in older adults improves psychomotor processing abilities and is associated with greater brain activation. It is not known whether these associations are also significant for longer-term adherence to moderate-intensity activities. Methods. We measured the cross-sectional association of regular walking with brain activation while performing the digit symbol substitution test (DSST). Participants of the lifestyle interventions and independence for elders--pilot study were examined 2 years after completing a 1-year treatment, consisting of either PA or education in successful aging (SA). Data were obtained from 20 PA participants who reported having remained active for 2 years after the end of the treatment and from l0 SA participants who reported having remained sedentary during the same period (mean age: 81.5 and 80.8 years). Complete brain activation and behavioral data were available for 17 PA and l0 SA participants. Results. Two years after the formal intervention had ended, the PA group engaged in more minutes of moderate activity and had significantly greater DSST score and higher brain activation within regions important for processing speed (left dorsolateral prefrontal, posterior parietal, and anterior cingulate cortices). Associations were independent of selfreported health, blood pressure, cognition, medication records, gray matter atrophy, and white matter hyperintensities. Conclusions. Persistent engagement in PA may have beneficial effects on psychomotor processing speed and brain activation, even for moderate levels and even when started late in life. Future studies are warranted to assess whether these beneficial effects are explained by delayed neuronal degeneration and/or new neurogenesis. doi: 10.1093/gerona/glq038

Background. Elevated systemic levels of myeloperoxidase (MPO) have been associated with unfavourable clinical outcomes. In the present study, we evaluate the impact of MPO, a pro-oxidant enzyme that catalyzes the initiation of lipid peroxidation and affects nitric oxide levels, on the risk of all-cause mortality in a large population of frail octogenarians and nonagenarians living in community. Methods. We analyzed data from the Aging and Longevity Study in the Sirente Geographic Area (ilSIRENTE Study), a prospective cohort study that collected data on all individuals aged 80 years and older living in a mountain community (n = 363). The main outcome measure was the risk of death after 4 years of follow-up. Participants were divided into three groups based on MPO tertiles: lower tertile [less than or equal to] 61.5 [micro]g/L (n = 120), intermediate tertile 61.6-140.6 [micro]g/L (n = 120), and higher tertile [greater than or equal to] 140.7 [micro]g/L (n = 123). Results. A total of 150 deaths occurred during 4-years follow-up. The mean MPO level was 170.8 [+ or -] 177.5 [micro]g/L among those who died compared with 135.4 [+ or -] 142.4 [micro]g/L among survivors (p = .03). Individuals in the highest MPO tertile had higher risk of mortality (40% [60/123]) compared with those in the lower tertile (26% [39/120]). After adjusting for potential confounders, compared with participants in the lower tertile, those in the higher tertile had a hazard ratio for mortality of 1.97 (95% confidence interval: 1.02-3.80). Conclusion. Our results obtained from a representative sample of very old and frail elderly individuals expand the knowledge that low levels of MPO are associated with better survival. Key Words: Myeloperoxidase--Mortality--Frail elderly. doi: 10.1093/gerona/glp183

Background. There is growing evidence that higher levels of inflammatory markers are associated with physical decline in older persons, possibly through the catabolic effects of inflammatory markers on muscle. The aim of this study was to investigate the association between serum levels of inflammatory markers and loss of muscle mass and strength in older persons. Methods. Using data on 2,177 men and women in the Health, Aging, and Body Composition Study, we examined 5-year change in thigh muscle area estimated by computed tomography and grip and knee extensor strength in relation to serum levels of interleukin-6 (IL-6), C-reactive protein, tumor necrosis factor-alpha (TNF-[alpha]), and soluble receptors (measured in a subsample) at baseline. Results. Higher levels of inflammatory markers were generally associated with greater 5-year decline in thigh muscle area. Most associations, with the exception of soluble receptors, were attenuated by adjustment for 5-year change in weight. Higher TNF-[alpha] and interleukin-6 soluble receptor levels remained associated with greater decline in grip strength in men. Analyses in a subgroup of weight-stable persons showed that higher levels of TNF-[alpha] and its soluble receptors were associated with 5-year decline in thigh muscle area and that higher levels of TNF-[alpha] were associated with decline in grip strength. Conclusions. TNF-[alpha] and its soluble receptors showed the most consistent associations with decline in muscle mass and strength. The results suggest a weight-associated pathway for inflammation in sarcopenia. Key Words: Muscle--Inflammatory markers--Aging--Weight. doi: 10.1093/gerona/glp097

Inhibition of the TOR signalling pathway by genetic or pharmacological intervention extends lifespan in invertebrates, including yeast, nematodes and fruitflies (1-5); however, whether inhibition of mTOR signalling can extend lifespan in a mammalian species was unknown. Here we report that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age. On the basis of age at 90% mortality, rapamycin led to an increase of 14% for females and 9% for males. The effect was seen at three independent test sites in genetically heterogeneous mice, chosen to avoid genotype-specific effects on disease susceptibility. Disease patterns of rapamycin-treated mice did not differ from those of control mice. In a separate study, rapamycin fed to mice beginning at 270 days of age also increased survival in both males and females, based on an interim analysis conducted near the median survival point. Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both. To our knowledge, these are the first results to demonstrate a role for mTOR signalling in the regulation of mammalian lifespan, as well as pharmacological extension of lifespan in both genders. These findings have implications for further development of interventions targeting mTOR for the treatment and prevention of age-related diseases., Because incidences of most diseases rise rapidly with age (6), interventions that delay ageing would greatly benefit health 7,8. So far, dietary additives that delay ageing and increase lifespan in [...]

Background. Cognitive impairment is an important contributor to disability. Limited clinical trial evidence exists regarding the impact of physical exercise on cognitive function (CF). We report results of a pilot study to provide estimates of the relative impact of physical activity (PA) on l-year changes in cognitive outcomes and to characterize relationships between changes in mobility disability and changes in cognition in older adults at increased risk for disability. Methods. Sedentary persons (102) at increased risk for disability (aged 70-89 years) were randomized to moderate_intensity PA or health education. Participants were administered the Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), modified Stroop test, and Modified Mini-Mental State Examination at baseline and 1 year. Results. Group differences were not significant but improvements in cognitive scores were associated with improvements in physical function. Specifically, the DSST significantly correlated with change in the Short Physical Performance Battery score (r = .38, p = .0002), in chair stand score (r = .26, p = .012), in balance score (r = .21, p = .046), and in 400-m gait speed (r = .15, p = .147). Change recall on the RAVLT and in the Stroop test was also positively correlated with changes in chair stand and balance, respectively. Conclusions. These results provide further support for the benefits of exercise on CF in older adults. An adequately powered clinical trial of PA involving older adults at increased risk for cognitive disability is needed to expand the indications for prescribing exercise for prevention of decline in brain function. Key Words: Exercise--Cognition--Aging--Prevention--LIFE study.

Background. Chronic subclinical inflammation may contribute to impaired physical function in older adults; however, more data are needed to determine whether inflammation is a common mechanism for functional decline, independent of disease or health status. Methods. We examined associations between physical function and inflammatory biomarkers in 542 older men and women enrolled in four clinical studies at Wake Forest University between 2001 and 2006. All participants were at least 55 years and had chronic obstructive pulmonary disease, congestive heart failure, high cardiovascular risk, or self-reported physical disability. Uniform clinical assessments were used across studies, including grip strength; a Short Physical Performance Battery (SPPB; includes balance, 4-m walk, and repeated chair stands): inflammatory biomarker assays for interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-[alpha]), and C-reactive protein (CRP); and anthropometric Measures. Results. Higher levels of CRP and IL-6, but not TNF-[alpha]. were associated with lower grip strength and SPPB scores and longer times to complete the 4-m walk and repeated chair stands tests, independent of age, gender, and race. More importantly, these relationships were generally independent of disease status. Further adjustment for fat mass, lean mass, or percent body fat altered some of these relationships but did not significantly change the overall results. Conclusions. Elevated CRF and IL-6 levels are associated with poorer physical function in older adults with various comorbidities, as assessed by a common battery of clinical assessments. Chronic subclinical inflammation may be a marker of functional limitations in older persons across several diseases/health conditions. Key Words: Inflammation--Physical function--Aging--Comorbidities.

Background. Sarcopenia, the age-related loss of muscle mass, may not be an isolated process but is associated with an increase in fat mass. The aim of this study was to estimate the mortality risk of sarcopenia in the presence or absence of obesity. Methods. Data are from 934 participants aged 65 years or older, enrolled in the 'Invecchiare in Chianti' study, and followed for 6 years. At baseline, a peripheral quantitative computerized tomography (pQCT) scan was performed on all participants to evaluate the muscle density, and the muscular and fat cross-sectional areas of the calf. Walking speed was measured on a 7-m track. Cox proportional hazard models were performed to estimate the association of pQCT measures (per 1 standard deviation increase) with mortality. Results. Unadjusted analyses showed significant associations of muscle density (hazard ratio [HR] 0.78. 95% confidence interval [CI] 0.69-0.88), muscle area (HR 0.75, 95% CI 0.66-0.86), and fat area (HR 0.82, 95% CI 0.73-0.92) with mortality. After adjustment for potential confounders, no body composition parameter was significantly associated with mortality. Walking speed (used as a reference measure to verify whether the negative results were due to peculiarities of the study sample) confirmed its well-established association with mortality risk (HR 0.73, 95% CI 0.60-0.88). These results did not change after the analyses were stratified according to sarcopenia and body mass index groups, and restricted to participants with frailty or a high inflammatory profile. Conclusions. Calf skeletal muscle and fat mass are not significant risk factors for mortality in community-dwelling older adults. Walking speed confirmed to be a powerful predictor of health-related events. Key Words: Skeletal muscle--Body composition--Fat mass--Walking speed--Obesity--Sarcopenia--Mortality--InCHIANTI.

Background. The metabolic syndrome includes dyslipidemia, abdominal obesity, insulin resistance, and hypertension and is associated with an increased risk of diabetes and cerebrovascular disease (CVD), but consequences beyond these outcomes have not been examined extensively. We investigated whether metabolic abnormalities have independent consequences on loss of mobility function of older persons. Methods. Data are from 2,920 men and women, 70-79 years, participating in the Health ABC study without mobility limitations at baseline. Metabolic syndrome was defined as [greater than or equal to]3 of the following: (a) waist circumference >102 (men) or >88 cm (women); (b) triglycerides [greater than or equal to]150 mg/dL; (c) high-density lipoprotein cholesterol Results. The prevalence of metabolic syndrome was 38.6%. The metabolic syndrome was associated with an adjusted relative risk (RR) of 1.46 (95% confidence interval [CI] = 1.30-1.63) for developing mobility limitations. The risk increased when more metabolic syndrome components were present (p trend >.001). All metabolic syndrome components were significantly associated with incident mobility limitations with the highest RRs for abdominal obesity (RR= 1.54, 95% CI = 1.35-1.75) and hyperglycemia (RR = 1.44, 95% CI = 1.27-1.63). Findings were unchanged when persons with baseline, or incident, CVD, stroke, or diabetes were excluded. Conclusions. Metabolic syndrome abnormalities, especially abdominal obesity and hyperglycemia, are predictive of mobility limitations in the elderly, independent of CVD or diabetes. Key Words: Metabolic syndrome--Obesity--G1ucose--Mobility limitation--Older--Diabetes--Cerebrovascular disease.

We examined the hypothesis that physical activity will have favorable effects on measures of self-efficacy for a 400-m walk and satisfaction with physical functioning in older adults 70+ years of age who have deficits in mobility. We randomized a total of 412 adults aged 70-89 years at elevated risk for mobility disability to either a physical activity or a successful aging educational control intervention for 12 months. Participants in the physical activity intervention had more favorable changes in both outcomes as a result of treatment than those in the successful aging intervention. Gender, age, and scores on a short physical performance battery did not moderate these effects. Physical activity is an effective means of intervening on self-efficacy and satisfaction with physical function in older adults with impaired lower extremity functioning. This is an important finding in light of the importance of these process variables in behavior change and quality of life. Key Words: Self-efficacy--Aging--Disability--Mobility--Quality of life.

Background. Clinical trials to assess interventions for mobility disability are critically needed; however, data for efficiently designing such trials are lacking. Methods. Results are described from a pilot clinical trial in which 424 volunteers aged 70-89 years were randomly assigned to one of two interventions--physical activity or a healthy aging education program--and followed for a planned minimum of 12 months. We evaluated the longitudinal distributions of four standardized outcomes to contrast how they may serve as primary outcomes of future clinical trials: ability to walk 400 meters, ability to walk 4 meters in [less than or equal to] 10 seconds, a physical performance battery, and a questionnaire focused on physical function. Results. Changes in all four outcomes were interrelated over time. The ability to walk 400 meters as a dichotomous outcome provided the smallest sample size projections (i.e., appeared to be the most efficient outcome). It loaded most heavily on the underlying latent variable in structural equation modeling with a weight of 80%. A 4-year trial based on the outcome of the 400-meter walk is projected to require N= 962-2234 to detect an intervention effect of 30%-20% with 90% power. Conclusions. Future clinical trials of interventions designed to influence mobility disability may have greater efficiency if they adopt the ability to complete a 400-meter walk as their primary outcome.

Depression in older persons represents a major issue because of its relevant prevalence and the associated higher risk of adverse health-related events. The aim of this study was to evaluate the relationship of depressive symptoms with measures of physical performance, muscle strength, and functional status. Data are from baseline evaluation of the ilSIRENTE Study (n = 364). Physical performance was assessed using the Short Physical Performance Battery and the 4-meter walking test. Muscle strength was measured by hand-grip strength. Functional performance was assessed using Basic and Instrumental Activities of Daily Living. Depression was defined by analyzing the different depressive manifestations included in the Minimum Data Set for Home Care Form: verbal expression of sad and/or anxious mood and demonstrated signs of mental distress. Analyses of covariance and linear regressions were performed to evaluate the relationship between depression and physical function. Participants with depression showed significantly worse results in all of the physical function tests. Subjects with depression presented significantly lower adjusted mean results for the 4-meter walking test (0.41 m/s; SE, 0.03) and the Short Physical Performance Battery score (5.68; SE, 0.38) compared with those without depression (0.50 m/s; SE, 0.01 and 6.93; SE, 0.21; all P Keywords: geriatrics; functional status; depression; clinical epidemiology, Depression in older persons represents a major issue because of its relevant prevalence and the associated higher risk of adverse health-related events. Many epidemiologic studies have documented that a high [...]

Background. Psychosocial factors have been associated with metabolic abnormalities that increase the risk of cardiovascular disease and diabetes. This study investigated the cross-sectional relationship between psychosocial risk factors and the metabolic syndrome in a community-based sample of older persons. Methods. Participants were 2917 persons aged 70-79 years enrolled in the Health, Aging and Body Composition study. Depressive and anxiety symptoms, negative life events, and inadequate emotional support were assessed, and a summary psychosocial risk index was calculated. Metabolic syndrome was defined as three or more of the following criteria: abdominal obesity, high triglycerides, low high-density lipoprotein (HDL) cholesterol, high fasting glucose, and high blood pressure. Results. Negative life events and inadequate emotional support increased the odds of having metabolic syndrome after adjustment for demographic and lifestyle variables (odds ratio [OR] per life event = 1.13, 95% confidence interval [CI] = 1.05-1.22; OR = 1.35, 95% CI = 1.10-1.66, respectively). The relationship between depressive symptoms and metabolic syndrome was only found in white (OR per standard deviation [SD] = 1.11, 95% CI = 1.01-1.23), but not in black (OR per SD = 0.97, 95% CI = 0.86-1.11) persons. Anxiety symptoms were significantly associated with metabolic syndrome in men (OR per SD = 1.13, 95% CI = 1.00-1.28), but not in women (OR per SD = 0.98, 95% CI = 0.89-1.08). Moreover, a higher score on the psychosocial risk index was associated with an increased probability of having the metabolic syndrome (OR = 1.30, 95% CI = 1.12-1.52). Conclusions. In the elderly population, different psychosocial risk factors are associated with a higher prevalence of the metabolic syndrome. Whether reduction or better management of psychosocial risk factors can improve the metabolic profile remains to be demonstrated.

A study to demonstrate that the ability to walk 400 m and timed performance discriminate mortality and cardiovascular risk and risk for mobility limitation and disability in community dwelling older adults without known difficulty performing mobility-related tasks is illustrated. The findings provide validation of the importance of having the capacity to walk longer distances and show that there is a wide range of function and risk in apparently well-functioning older adults.

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 36/17 (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.

Chronic inflammation is associated with the aging process and numerous age-related pathologies. We evaluated the effects of age, caloric restriction (CR), and exercise on plasma C-reactive protein (CRP), interleukin-6, and total antioxidant capacity in Fisher 344 rats. The inflammatory markers were analyzed using enzyme-linked immunosorbent assays (ELISA), while total antioxidant potential was determined by a spectrophotometric method. An increase in circulating levels of CRP with age was attenuated with long-term 40% CR; short-term 40% CR in young animals also reduced CRP concentration compared to age-matched controls. Lifelong exercise with 8% CR showed a marked decrease in CRP levels compared to 8% CR controls and an even greater reduction compared to ad libitum-fed rats. Plasma interleukin-6 levels remained unchanged with age, CR, and exercise, whereas inflammation levels showed an inverse association with plasma antioxidant status. These studies highlight the anti-inflammatory effects of CR and exercise.

The disablement process is often accompanied by sarcopenia or muscle loss, which is associated with virtually all identified disability risk factors. Clinically, the association between body composition and physical performance has been documented by several studies. However, loss of strength is greater than loss of muscle mass with age implying that the quality of remaining muscle may be reduced. Although there are limited data explaining potential physiological mechanisms that contribute to muscle quality, sarcopenia is frequently associated with fat accumulation, and the percentage of body fat increases with age even if weight does not. However, the relationship between fat and muscle function may not be linear, suggesting that there may be an optimal ratio of lean to fat mass for physical function. There are no definitive pharmacological interventions proven to prevent decline in physical function either by modulating body composition or by other means. One exception may be angiotensin-converting enzyme inhibitors (ACEIs). ACE is an important component of the renin-angiotensin system, the central hormonal regulator of blood pressure. Recent evidence suggests that ACEIs may improve physical function by means of direct effects on body composition in older persons, rather than through its blood-pressure-lowering effects. Clinical and genetic studies in humans and experimental evidence in animals suggest that modulation of the reninangiotensin system is associated with metabolic and biochemical changes in skeletal muscle and fat, changes that are associated with declining physical function. ACEIs may modulate this process through a variety of molecular mechanisms including their influence on oxidative stress and on metabolic and inflammation pathways. This review describes potential biological mechanisms of ACE inhibition and its contribution to declining physical performance and changing body composition. Promising pharmacoepidemiological studies and experimental evidence in animals suggest that there are appropriate models in which to study this effect.

Background. We determined whether physical function and its response to exercise training are associated with polymorphisms in cytokine genes (interleukin-6 [IL-6] -174 G/C; tumor necrosis factor alpha [TNF[alpha]] -308 G/A and -238 G/A; and TNF[alpha] receptors [TNFR]1 +36 A/G, TNFR2 +676 T/G, and TNFR2-1663 A/G), in 214 older ([greater than or equal to] 60 years), overweight (body mass index [greater than or equal to] 28 kg/[m.sup.2]) individuals with knee osteoarthritis. Methods. Physical function (walking distance, stair-climb time, self-reported disability) was measured before and after an 18-month randomized, controlled exercise trial involving walking and weight lifting 3 days/week. Results. In cross-sectional analyses, baseline walking distance was greater in individuals homozygous for the major G allele at IL-6 -174 compared to individuals with at least one C allele (p = .05). Both walking distance (p = .02) and stair-climb time (p = .003) were better in individuals homozygous for the major G allele of the TNF[alpha] -308 polymorphism compared to those with at least one A allele. Walking distance was better (p = .02), and stair-climb time tended to be better (p = .06), in individuals homozygous for the major T allele of the TNFR2 +676 polymorpbism. No associations were seen with self-reported physical disability nor with the other polymorphisms. In response to exercise, there was a significant interaction between TNF[alpha]-308 genotype and exercise treatment on 6-month changes in stair-climb time (p.007), and on 18-month changes in self-reported physical disability (p = .01), such that individuals with an A allele showed greater improvement in response to exercise. Conclusions. Walking distance and stair climbing speed are partly influenced by genetic variation in the IL-6 and TNF[alpha] genes in older individuals with knee osteoarthritis.

Background. Depression is a common disorder among older adults, and it has been associated with adverse outcomes, including increased risk of morbidity and mortality as well as incomplete or delayed recovery from illness and disability. The objective of this study was to examine whether depressive symptoms and anemia are associated among older adults living in the community. Methods. We used data from the 'Invecchiare in Chianti' (Aging in the Chianti area, InCHIANTI) study, a prospective population-based study of older people living in the community. Anemia was defined by the World Health Organization (WHO) criteria: hemoglobin concentration below 12 g/dl in women and below 13 g/dl in men. Depressive symptoms were measured by using the Center for Epidemiological Studies Depression Scale (CES-D). Participants with a CES-D score [greater than or equal to]16 were considered to be depressed. Results. Mean age of the 986 participants was 75 years, and 56% were female; 313 (32%) study participants were depressed. Anemia was recorded in 48 of the 313 (15%) participants with depression and in 53 of the 673 (8%) participants without depression (p < .001). After adjusting for potential confounders, depression was associated with a significant higher risk of anemia (odds ratio = 1.93; 95% confidence interval, 1.19-3.13). The risk of anemia progressively and significantly increased with increasing CES-D score (signifying more severe depression). Compared with nondepressed participants (CES-D score 26), respectively (p for linear trend=.01). Conclusions. Depressive symptoms are associated with anemia in a general population of older persons living in the community.

A study is conducted to determine whether the angiotensin-converting enzyme (ACE) genotype interacts with significant physical activity to affect the incidence of mobility limitation in well-functioning older adults. The findings indicate that older individuals who exercised with ACE are less likely to develop mobility limitation than those who did not exercise.

Background. Physical performance measures can predict incident disability, but little research has assessed and compared how these measures predict progressive and rapid-onset (catastrophic) disability. The authors evaluated the ability of upper and lower extremity performance measures to predict progressive and catastrophic disability in activities of daily living (ADL), mobility, and upper extremity function. Methods. The incidence of progressive and catastrophic disability was assessed semiannually during a 3-year period in 884 women participating in the Women's Health and Aging Study I. Four-meter walking speed, balance, and chair stands tests were used to evaluate lower extremity function. The putting-on-blouse test, the Purdue pegboard test, and grip strength were used to assess upper extremity function. Summary performance scores (SPS) for the lower and upper extremities were calculated. Among participants in whom disability developed, those who reported no difficulty in the previous year were defined as cases of catastrophic disability, and those who previously reported little or some difficulty were considered to be cases of progressive disability. Cox proportional hazard regression analyses were used to evaluate the association of performance measures and time to incident disability. The predictive ability of performance measures was compared using receiver-operator characteristic curves. Results. All lower and upper extremity measures, with the exception of grip strength, significantly predicted the onset of progressive ADL disability, but only walking speed was significantly associated with the onset of catastrophic ADL disability. The chair stands test, walking speed, and the lower extremity SPS were significantly associated with the onset both progressive and catastrophic mobility disability. Only lower extremity individual tests and SPS significantly predicted the onset of both progressive and catastrophic upper extremity disability. The receiver-operator characteristic curves for ADL and mobility disability showed that all performance measures evaluated had a greater predictive ability for progressive than for catastrophic incident disability. This finding was not consistent for upper extremity disability. The areas under the curve for walking speed and lower extremity SPS were very similar, ranging from 0.58 to 0.81 and from 0.57 to 0.85, and the predictive ability of these two measures was the greatest for all disability outcomes assessed. Conclusion. Physical performance measures of lower extremity and, in particular, walking speed and lower extremity SPS are valuable tools to predict different forms of disability, especially those with a progressive onset.

Background. There is a lack of information on the effects of angiotensin-converting enzyme (ACE) inhibitors in very old people with heart failure (HF). The objective of this study is to estimate the prevalence of prescriptions of ACE inhibitors in elderly people with HF discharged from acute care hospitals, and to evaluate the effect of these drugs on 1-year mortality rates. Methods. We used data from the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA). In 1998, we undertook a l-year longitudinal study on elderly people (aged 65+ years) discharged with a diagnosis of HF. We compared the demographic and clinical characteristics associated with a prescription at discharge of ACE inhibitors, and used a Cox proportional hazard regression model to calculate the relative hazard of dying associated with the use of ACE inhibitors. Results. We enrolled 818 patients in the study with a mean age of 79 years (range: 65-101 years). One fourth of the participants were aged 85 years or older. ACE inhibitors were prescribed to 550 patients (67.2%) at discharge. Older age and physical disability were negatively correlated with the use of ACE inhibitors. People using ACE inhibitors had a 40% reduction of mortality (HR [hazard ratio]: 0.60: 95% CI [confidence intervals]: 0.42-0.88). The reduction in mortality was much stronger among disabled people (HR: 0.35: 95% CI: 0.19-0.64). Conclusion. ACE inhibitors are still underprescribed among elderly people with HF discharged from acute care hospitals. Even in this frail, elderly population, we found a beneficial effect of ACE inhibitors. There is room to further improve the quality of care for elderly people with HF.

This study was designed to test the effects of angiotensin-converting enzyme (ACE) inhibition on body composition and physical performance in aged rats. Male Brown Norway x F344 rats were randomized to receive daily injections of enalapril (40 mg/kg or 80 mg/kg) or saline from 24 to 30 months of age. Body composition was determined using dual-energy X-ray absorptiometry (DXA), and physical performance was assessed using the grip strength and inclined plane procedures. Performance measures were assessed at baseline and monthly thereafter. DXA was performed at baseline, 3 months, and 6 months of follow-up. Compared with the enalapril groups, the saline group experienced a greater 6-month decline in the physical performance measures. Lean body mass declined in both groups; however, the enalapril groups also experienced a significant loss of fat mass. These results suggest that ACE inhibition may prevent age-related declines in physical performance, which may be mediated by a reduction in body fat mass.

Background, Anemia is associated with reduced physical performance and muscle strength. The aim of the study was to explore whether anemia and hemoglobin levels are associated with differences in quantitative and qualitative measures of muscle and fat. Methods, The study sample consisted of 909 participants 65 years and older enrolled in the 'lnvecchiare in Chianti' (InCHIANTI) study, a prospective population-based study of older people aimed at identifying risk factors for late-life disability. All the analyses were performed considering continuous hemoglobin levels as well as the dichotomous anemia variable (defined according to World Health Organization criteria as hemoglobin Results. Participants were aged 74.8 [+ or -] 6.8 years. In our sample, 94 participants (10.3%) were anemic. Hemoglobin levels were significantly associated with muscle density ([beta] = 0.225 [SE, standard error 0.098], p = .02), muscle area/total area ratio ([3 = 0.778 [SE 0.262], p = .003), fat area/total area ratio (13 = -4.869 [SE 0.225]; p < .001). Skeletal muscle strength and muscle density were highly associated with anemia (13 =-3.266 [SE 1.173], p = .005 and [beta] = -0.816 [SE 0.374], p = .03, respectively). Results did not change when analyses were rerun in a restricted sample of participants not affected by major medical conditions. Conclusion. The present study shows that hemoglobin levels are associated with the parameters of body composition obtained by pQCT, and that decreases in muscular strength measures occur in the presence of anemia.

Background. Some studies have proposed chronic inflammation as an underlying biological mechanism responsible for physical function decline in elderly people. The aim of this study is to evaluate the relationship between several inflammatory markers and physical performance in an older population. Methods, This study is part of the 'Invecchiare in Chianti' (InCHIANTI) study, a prospective population-based study of older people, aimed at identifying risk factors for late-life disability. The study sample consisted of 1020 participants aged 65 years and older living in the Chianti area of Italy. Physical performance was assessed using walking speed, the chair-stand test, and the standing balance test. Hand-grip strength was assessed using a hand-held dynamometer. Serum levels of C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor-alpha (TNF-[alpha]), IL-10, IL-1[beta], IL-6sR, and IL-1RA were determined. Linear regression analyses were used to assess the multivariate relationship of inflammatory marker levels with physical performance, scored as a continuous variable from 0 to 3, and hand-grip strength after adjustment for demographics, chronic conditions, medication use, and other biological variables. Results. CRP, IL-6, and IL1RA were significantly correlated with physical performance (r= 0.162, r= -0.251, and r= -0.127, respectively). Significant correlations with hand-grip strength were found for CRP and IL-6 (r= -0.081 and r = -0.089. respectively). After adjustment for covariates, high levels of IL-6 and IL-IRA continued to be strongly associated with worse physical performance (p < .001 and p = 0.004, respectively). High levels of CRP (p < .001) and IL-6 (p < .001) were associated with low hand-grip strength. Mean adjusted physical performance scores ranged from 2.21 in the CRP < 0.59 mg/dl group to 2.07 in the CRP > 0.60 mg/dl group (p for trend = .004). and front 2.25 in the lowest IL-6 quartile to 2.08 in the highest IL-6 quartile (p for trend < .001). This trend was also reflected in mean adjusted handgrip strength, with a range from 28.8 kg for the CRP < 0.59 mg/dl group to 26.0 kg for the CRP > 0.60 mg/dl group (p for trend = .001), and from 27.4 kg for the lowest IL-6 quartile to 25.1 kg for the highest IL-6 quartile (p for trend = .001). Conclusions. Inflammation, measured as high levels of 1L-6, CRP, and IL-1RA, is significantly associated with poor physical performance and muscle strength in older persons. These data also support the biological face validity of physical performance measures. The assessment of inflammatory markers may represent a useful screening test and perhaps a potential target of intervention.

Low-dose diuretics should be the first drug used to treat all patients with high blood pressure, according to a review of 42 clinical trials covering 192,478 patients. Low-dose diuretics were more effective in reducing the risk of coronary heart disease, heart attack, stroke, and congestive heart failure than other antihypertensive drugs such as calcium channel blockers, beta blockers, ACE inhibitors, and alpha blockers.

Background. A decline in muscle mass and muscle strength characterizes normal aging. As clinical and animal studies show a relationship between higher cytokine levels and low muscle mass, the aim of this study was to investigate whether markers of inflammation are associated with muscle mass and strength in well-functioning elderly persons. Methods. We used baseline data (1997-1998) of the Health, Aging, and Body Composition (Health ABC) Study on 3075 black and white men and women aged 70-79 years. Midthigh muscle cross-sectional area (computed tomography), appendicular muscle mass (dual-energy x-ray absorptiometry), isokinetic knee extensor strength (KinCom), and isometric grip strength were measured. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-[alpha] (TNF-[alpha]) were assessed by enzyme-linked immunosorbent assay (ELISA). Results. Higher cytokine levels were generally associated with lower muscle mass and lower muscle strength. The most consistent relationship across the gender and race groups was observed for IL-6 and grip strength: per SD increase in IL-6, grip strength was 1.1 to 2.4 kg lower (p < .05) after adjustment for age, clinic site, health status, medications, physical activity, smoking, height, and body fat. An overall measure of elevated cytokine level was created by combining the levels of IL-6 and TNF-[alpha]. With the exception of white men, elderly persons having high levels of IL-6 (> 1.80 pg/ml) as well as high levels of TNF-[alpha] (>3.20 pg/ml) had a smaller muscle area, less appendicular muscle mass, a lower knee extensor strength, and a lower grip strength compared to those with low levels of both cytokines. Conclusions. Higher plasma concentrations of IL-6 and TNF-[alpha] are associated with lower muscle mass and lower muscle strength in well-functioning older men and women. Higher cytokine levels, as often observed in healthy older persons, may contribute to the loss of muscle mass and strength that accompanies aging.

Background. Although lower and upper extremity performance measures are widely used and represent validated physical function measures in older adults, there is limited information regarding the magnitude of changes in these measures over time. This study (i) assesses prospective changes in physical performance measures, (ii) defines a summary score that demonstrates a significant amount of change over time, and (iii) examines rates of decline according to age arid baseline performance levels. Methods. Data from the Women's Health and Aging Study (WHAS) were analyzed to assess change in the one third most disabled older women living in the community. Lower extremity function was assessed using walking speed, balance, and chair stands tests. The putting-on-blouse test, the lock and key test, the Purdue Pegboard test, and grip strength were used to gauge upper extremity function. Continuous and categorical summary performance scores were calculated using continuous and categorical data of lower and upper performance measures. Results. After 3 years, lower extremity performance measures declined by 16%-27%, while upper extremity performance measures declined less (7%-24%). For lower extremity function, the continuous summary performance score showed a slightly greater 3-year decline from baseline (decline vs baseline mean: 23%; decline vs SD of the baseline mean: 59%) than the categorical score (22% and 41%, respectively). Older age and intermediate level of baseline performance were associated with the greatest decline, especially for lower extremity function. Conclusions. In moderately to severely disabled women aged 65 or older, lower extremity measures show more change over 3 years than upper extremity measures. Among the lower extremity summary scores, the continuous score changes more over time than the categorical score with respect to the baseline SD. The lower extremity continuous summary performance score may be a useful outcome measure for clinical studies of physical performance in older women.

In humans, physical performance declines with increasing age, and in nondisabled older persons, scores on standardized performance measures, such as walking speed, repeated chair stands, and a balance test, predict the incidence of disability and reduced longevity. Here we show in aged rats (24-month-old Brown Norway x Fischer 344 male rats; n = 48) that conceptually similar performance measures, such as swimming speed and an inclined plane procedure, can be assessed longitudinally, and that over 6 months of follow-up from the age of 24 to 30 months, performance declines progressively with increasing age. High baseline performance scores predict long-term longevity, a relationship that is also found in humans. The application of standardized physical performance measures to a variety of animal models of aging may help to define similarities between species in the underlying mechanisms of the age-related decline in performance, disability, and longevity.

This study examines and compares the effect of aerobic and resistance exercise on emotional and physical function among older persons with initially high or low depressive symptomatology. Data are from the Fitness, Arthritis and Seniors Trial, a trial among 439 persons 60 years or older with knee osteoarthritis randomized to health education (control), resistance exercise, or aerobic exercise groups. Depressive symptoms (assessed by the Center for Epidemiologic Studies-Depression scale) and physical function (disability, walking speed, and pain) were assessed at baseline and after 3, 9, and 18 months. Compared with results for the control group, aerobic exercise significantly lowered depressive symptoms over time. No such effect was observed for resistance exercise. The reduction in depressive symptoms with aerobic exercise was found both among the 98 participants with initially high depressive symptomatology and among the 340 participants with initially low depressive symptomatology and was the strongest for the most compliant persons. Aerobic and resistance exercise significantly reduced disability and pain and increased walking speed both, and to an equal extent, in persons with high depressive symptomatology and persons with low depressive symptomatology.

Background. Hypokalemia is a common finding among older patients taking diuretic medications. However, it is not known whether older age per se carries an increased risk of hypokalemia, particularly during a patient's treatment with loop diuretics. Methods. The association between age and incident hypokalemia was examined in 18,872 patients with normal baseline serum potassium enrolled during three yearly multicenter surveys; 4,035 patients started receiving loop diuretics during their hospital stay. Demographic variables, comorbid conditions, medications, and objective tests that were associated with incident hypokalemia in separate age- and sex-adjusted logistic regression models were examined as potential confounders. Results. Among patients with normal baseline serum potassium, the factors of age, presence of coronary disease or diabetes, comorbidity, the use of ACE inhibitors, loop diuretics, digitalis, corticosteroids, or insulin, and baseline serum potassium were associated with incident hypokalemia in initial models. After these variables were adjusted for, age (for each decade, odds ratio = 1.30; 95% confidence interval = 1.17-1.46; p < .0001) was associated with incident hypokalemia. The use of parenteral (2.30; 1.53-3.46; p < .0001) but not oral (1.16; 0.79-1.69; p = .44) loop diuretics was associated with hypokalemia. Eventually, age was associated with hypokalemia when the summary regression model was analyzed in patients taking loop diuretics (1.33; 1.03-1.71;p = .027), as well as in those taking intravenous loop diuretics only (1.84; 1.25-2.70; p = .002). Conclusions. Older age is independently associated with the in-hospital development of hypokalemia, particularly among patients taking loop diuretics. Monitoring of serum potassium levels is therefore advisable when older patients are treated with these agents.

Hospital-based interventions to reduce the disability associated with several diseases could reduce health care costs. Researchers interviewed 6,070 people annually and analyzed hospitalization rates and Medicare charges when any participant developed a disability. Seventy-two percent of those who developed a sudden disability were hospitalized in the year of the disability compared to 48.6% of those who developed a progressive disability. Only 6 diseases accounted for two-thirds of the hospitalizations, including stroke, hip fracture, heart failure and cancer., Objective.--To characterize hospital diagnoses, procedures and charges, and nursing home admissions in the year when older persons become severely disabled, comparing those in whom severe disability develops rapidly with those in whom disability develops gradually. Design.--A prospective; population-based cohort study with at least 6 annual interviews beginning in 1982. Setting.--A total of 3 communities: East Boston, Mass, New Haven, Conn, and Iowa and Washington counties in Iowa. Subjects.--A total of 6070 persons at least 70 years old with at least 1 interview after the fourth annual follow-up and without evidence of previous severe disability, defined as disability in 3 or more activities of daily living (ADLs). Main Outcome Measures.--Characteristics associated with development of severe disability after the fourth annual follow-up, in which the disability is classified as catastrophic disability if the individual did not report any ADL disability in the 2 interviews prior to severe disability onset or as progressive disability if the individual had previous disability in 1 or 2 ADLs. Results.--In the year during which severe disability developed, hospitalizations were documented for 72.1% of those developing catastrophic disability and for 48.6% of those developing progressive disability. In the corresponding year, only 14.7% of those who were stable with no disability and 22.3% of those with some disability were hospitalized. The 6 most frequent principal discharge diagnoses included stroke, hip fracture, congestive heart failure, and pneumonia in both severe disability subsets; coronary heart disease and cancer in catastrophic disability; and diabetes and dehydration in progressive disability. These diagnoses occurred in 49% of those with catastrophic disability and 25% of those with progressive disability. In both severe disability subsets, the oldest patients received less intensive hospital care as indicated by charges for surgery, diagnostics, and rehabilitation and by the percentage who received major diagnostic procedures; they were also more often admitted to nursing homes. Conclusions.--In the year when they become severely disabled, a large proportion of older persons are hospitalized for a small group of diseases. Hospital-based interventions aimed at reducing the severity and functional consequences of these diseases could have a large impact on reduction of severe disability. JAMA. 1997;277:728-734

Introduction Ageing has been associated with numerous physiological changes, some of which are caused by the cumulative effects of pathological conditions such as hypertension, atherosclerosis, and diabetes, and others that [...]