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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

Background. It is unclear if physical activity (PA) can prevent or reverse frailty. We examined different doses and types of PA and their association with the onset and severity of frailty. Methods. Health, Aging and Body Composition (Health ABC) study participants (N = 2,964) were followed for 5 years, with frailty defined as a gait speed of less than 0.60 m/s and/or inability to rise from a chair without using one's arms. Individuals with one impairment were considered moderately frail and those with both severely frail. We examined PA doses of volume and intensity, activity types (eg, lifestyle vs exercise activities), and their associations with incident frailty and transition to severe frailty in those who became frail. Results. Adjusted models indicated that sedentary individuals had significantly increased odds of developing frailty compared with the exercise active group (adjusted odds ratio [OR] = 1.45; 95% confidence interval [CI]: 1.04-2.01), whereas the lifestyle active did not. Number of diagnoses was the strongest predictor of incident frailty. In those who became frail during follow-up (n = 410), there was evidence that the sedentary (adjusted OR = 2.80; 95% CI: 0.98-8.02) and lifestyle active (adjusted OR = 2.81; 95% CI: 1.22-6.43) groups were more likely to have worsening frailty over time. Conclusions. Despite the strong relationship seen between comorbid conditions and onset of frailty, this observational study suggests that participation in self-selected exercise activities is independently associated with delaying the onset and the progression of frailty. Regular exercise should be further examined as a potential factor in frailty prevention for older adults. Key Words: Aging--Exercise--Frail elderly--Longitudinal studies.

Background. Reported fatigue has been identified as a component of frailty. The contribution of nighttime sleep quality (duration and complaints) to fatigue symptoms in community-dwelling older adults has not been evaluated. Methods. We studied 2264 men and women, aged 75-84 years (mean 77.5 years; standard deviation [SD] 2.9), participating in the Year 5 (2001-2002) clinic visit of the Health, Aging, and Body Composition (Health ABC) study. Fatigue was determined using a subscale of the Modified Piper Fatigue Scale (0-50; higher score indicating higher fatigue). Hours of sleep per night, trouble falling asleep, waking up during the night, and waking up too early in the morning were assessed using interviewer-administered questionnaires. Results. The average fatigue score was 17.7 (SD 8.4). In multivariate models, women had a 3.8% higher fatigue score than men did. Individuals who slept [less than or equal to] 6 hours/night had a 4.3% higher fatigue score than did those who slept 7 hours/ night. Individuals with complaints of awakening too early in the morning had a 5.5% higher fatigue score than did those without these complaints. These associations remained significant after multivariate adjustment for multiple medical conditions. Conclusion. The association between serf-reported short sleep duration ([less than or equal to] 6 hours), and waking up too early and fatigue symptoms suggests that better and more effective management of sleep behaviors may help reduce fatigue in older adults. Key Words: Sleep--Fatigue--Aging.

Background. Mobility limitations are prevalent, potentially reversible precursors to mobility loss that may go undetected in older adults. This study evaluates standardized administration of an endurance walk test for identifying unrecognized and impending mobility limitation in community elders. Methods. Men and women (1480 and 1576, respectively) aged 70-79 years with no reported mobility limitation participating in the Health, Aging and Body Composition study were administered the Long Distance Corridor Walk. Wall performance was examined to determine unrecognized mobility deficits at baseline and predict new self-recognition of mobility limitation within 2 years. Results. On testing, 23% and 36% of men and women evidenced mobility deficits defined as a contraindication to exertion, meeting stopping criteria or exceeding 7 minutes to walk 400 m. Unrecognized deficits increased with age and were more prevalent in blacks, smokers, obese individuals, and infrequent walkers. Within 2 years, 21% and 34% of men and women developed newly recognized mobility limitation; those with baseline unrecognized deficits had higher rates, 40% and 54% (p < .001), respectively. For each additional 30 seconds over 5 minutes needed to walk 400 m, likelihood of newly recognized mobility limitation increased by 65% and 37% in men and women independent of age, race, obesity, smoking status, habitual walking, reported walking ease, and usual gait speed. Conclusions. A sizable proportion of elders who report no walking difficulty have observable deficits in walking performance that precede and predict their recognition of mobility limitation. Endurance walk testing can help identify these deficits and provide the basis for treatment to delay progression of mobility loss. Key Words: Mobility--Walking--Limitation--Endurance--Performance--Testing.

Background. Emerging evidence indicates an association between cognitive function and physical performance in late life. This study examines the relationship between cognitive function and subsequent gait speed decline among high-functioning older adults. Methods. Measures of global cognitive function (Modified Mini Mental State Examination [3MS]) and executive control function (ECF) (a clock drawing task [CLOX 1 ] and the 15-item Executive Interview [EXIT 15]) were obtained in the Health, Aging, and Body Composition Study in 1999-2000. Gait-speed (meters/second) was assessed over 20 meters at usual pace. Using a mixed model, we assessed the relationship between baseline cognitive function and gait-speed change over 3 years. Results. Two thousand, three hundred forty-nine older adults (mean age 75.6 [+ or -] 2.9 years) completed the assessments. After adjustment for baseline gait speed, a 1-standard-deviation (SD) lower performance on each cognitive test was associated with greater gait-speed decline over 3 years: 0.016 m/s for the 3MS (SD = 8.1), 0.009 m/s for CLOX 1 (SD = 2.4), and 0.012 m/s for EXIT 15 (SD = 4.1) (p < .0005 for all). After adjustment for comorbidities, the effect size was attenuated for 3MS and CLOX 1, and the association for EXIT 15 was no longer significant. Depression score was most strongly associated with the EXIT 15 effect reduction. Conclusion. Global and executive cognitive functions predict declines in gait speed. The association of ECF with gait speed decline is attenuated by comorbid conditions, particularly depression. Elucidation of the mechanisms underlying these associations may point to new pathways for the treatment of physical decline associated with diminished cognitive function.

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.

Background. This study examines the association between socioeconomic status (SES) and inflammatory markers in well-functioning older adults and seeks to determine whether any association remains after adjusting for biomedical and behavioral factors typically related to elevated serum levels of inflammatory markers. Methods. Data were obtained from 3044 men and women, aged 70-79 from Pittsburgh, Pennsylvania and Memphis, Tennessee participating in the Health, Aging and Body Composition study. Three indicators of SES were used: education, income, and ownership of financial assets. Serum levels of interleukin-6, C-reactive protein, and tumor necrosis factor-[alpha] were measured. Results. Low SES was associated with significantly elevated levels of interleukin-6, C-reactive protein, and tumor necrosis factor-[alpha] compared to high SES. Behavioral factors (including smoking, drinking, obesity) explained a substantial part of the inverse association between SES and inflammatory markers. Adjustment for prevalent diseases (including heart diseases, lung disease, and diabetes) associated with inflammation explained less of the association. Conclusions. This study suggests that interventions to improve health behaviors, even in old age and especially in low SES groups, may be useful in reducing risks associated with inflammation.

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-[alpha] considered as potential confounders. Results. There were 286 deaths over an average of 4.9 (standard deviation = 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.

Background. Obesity increases the risk for functional decline in later years, but the functional consequences of weight change in older adults are currently unclear. The aim of this study was to determine whether weight, weight change, and weight change intention are associated with risk for mobility limitation in elderly persons. Methods. This study included 2932 well-functioning black and white men and women aged 70 to 79 years, participating in the Health. Aging and Body Composition (Health ABC) Study, who were followed for 30 months. At baseline, reported weight change of 5 or more pounds during the previous year and weight change intention were assessed. Mobility limitation was defined as reported difficulty or inability to walk one-quarter mile or to climb 10 steps during two conservative semi-annual assessments during a period of 30 months. Results. Approximately 30% of participants developed mobility limitation. Higher body mass index (BMI) was associated with increased risk for mobility limitation. Unintentional weight loss in the previous year was associated with increased risk for mobility limitation in the extremely obese, which was defined as BMI [greater than or equal to] 35 (hazard ratios |HR| = 3-79; 95% confidence interval |CI|, 1.84-7.79), and the normal BMI, which was defined as BMI < 25 (HR, 2.55: 95% CI, 1.803.60). In persons with BM125 to 29.9, intentional weight loss (HR, 1.59; 95% CI, 1.12-2.25) and weight fluctuation with any intention (HR, 1.59: 95% CI, 1.10-2.28) increased the risk for mobility limitation. Unintentional weight gain or fluctuation did not confer additional risk for mobility Iimitation compared with weight stability, regardless of the level of body weight. Conclusion. In this cohort of well-functioning elderly persons, functional consequences of past weight change depended on the type of weight change, intentionality, and current measured body weight.

Background. The association between low socioeconomic status and poor physical functioning has been well described; biomedical factors may play an important role in explaining these differences. This study examines the association between socioeconomic status and incident mobility limitation in well-functioning older adults, and seeks to determine whether this link could be explained by biomedical factors. Methods. Data were obtained from 3066 men and women, aged 70-79 years from Pittsburgh, Pennsylvania and Memphis, Tennessee participating in the Health; Aging and Body Composition (Health ABC) study. Three indicators of socioeconomic status were used: education, income, and ownership of financial assets. Mobility limitation was defined as reporting difficulty walking 1/4 mile or climbing 10 steps during two consecutive semiannual assessments over 4.5 years. Biomedical factors included a wide range of diseases (e.g., heart and cerebrovascular disease) and biological risk factors (e.g. hypertension, poor pulmonary function, and high serum levels of inflammatory markers). Results. Adjusted hazard ratios of incident mobility limitation were significantly higher in those persons with low education, low income, and few assets. Hazard ratios ranged from 1.66 to 2.80 in the lowest socioeconomic groups. Additional adjustment for biomedical factors reduced the hazard ratios by an average of 41% for education, 17% for income, and 29% for assets. Conclusion. Biomedical factors can account for some of the association between socioeconomic status and incident mobility limitation. However, to reduce physical disabilities and, in particular, the socioeconomic differences therein, it may not be sufficient to solely intervene upon biological risk factors and risks of diseases.

Background. Lower muscle mass has been correlated with poor physical function; however, no studies have examined this relationship prospectively. This study aims to investigate whether low muscle mass, low muscle strength, and greater fat infiltration into the muscle predict incident mobility limitation. Methods. Our study cohort included 3075 well functioning black and white men and women aged 70-79 years participating in the Health, Aging, and Body Composition study. Participants were followed for 2.5 years. Muscle cross-sectional area and muscle tissue attenuation (a measure of fat infiltration) were measured by computed tomography at the mid-thigh, and knee extensor strength by using a KinCom dynamometer. Incident mobility limitation was defined as two consecutive self-reports of any difficulty walking one-quarter mile or climbing 10 steps. Results: Mobility limitations were developed by 22.3% of the men and by 31.8% of the women. Cox's proportional hazards models, adjusting for demographic, lifestyle, and health factors, showed a hazard ratio of 1.90 [95% confidence interval (CI), 1.27-2.84] in men and 1.68 (95% CI, 1.23-2.31) in women for the lowest compared to the highest quartile of muscle area (p < .01 for trend). Results for muscle strength were 2.02 (95% CI, 1.39-2.94) and 1.91 (95% CI, 1.41-2.58), p < .001 trend, and for muscle attenuation were 1.91 (95% CI, 1.31-2.83) and 1.68 (95% CI, 1.20-2.35), p < .01 for trend. When included in one model, only muscle attenuation and muscle strength independently predicted mobility limitation (p < .05). Among men and women, associations were similar for blacks and whites. Conclusion. Lower muscle mass (smaller cross-sectional thigh muscle area), greater fat infiltration into the muscle, and lower knee extensor muscle strength are associated with increased risk of mobility loss in older men and women. The association between low muscle mass and functional decline seems to be a function of underlying muscle strength.