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OBJECTIVE To determine whether long-term diet (D) and exercise (E) interventions, alone or in combination (D+E), have beneficial effects for older adults with knee osteoarthritis 3.5-years after the interventions end. METHODS This is a secondary analysis of a subset (N = 94) of the first 184 participants who had successfully completed the Intensive Diet and Exercise in Arthritis (IDEA) trial (N = 399) and who consented to follow-up testing. Participants were older (age ≥ 55 years), overweight and obese adults with radiographic and symptomatic knee osteoarthritis in at least one knee who completed 1.5-year D+E (N=27), D (N=35), or E (N=32) interventions and returned for 5-year follow-up testing an average of 3.5-years later. RESULTS During the 3.5-years following the interventions, weight regain in D+E and D was 5.9 kg (7%) and 3.1 kg (4%), respectively, with a 1 kg (1%) weight loss in E. Compared to baseline, weight (D+E, -3.7 kg, P=.0007; D, -5.8 kg, P

Heart failure (HF) and myocardial infarction are serious complications of major noncardiac surgery in older adults. Many factors can contribute to the development of HF during the postoperative period. The incidence of, and risk factors for, procedure-associated heart failure (PHF) occurring at the time of, or shortly after, medical procedures in a population-based sample ≥ 65 years of age have not been fully characterized, particularly in comparison with HF not proximate to medical procedures. This analysis comprises 5,121 men and women free of HF at baseline from the Cardiovascular Health Study who were followed up for 12.0 years (median). HF events were documented by self-report at semi-annual contacts and confirmed by a formal adjudication committee using a review of the participants' medical records and standardized criteria for HF. Incident HF events were additionally adjudicated as either being related or unrelated to a medical procedure (PHF and non-PHF, respectively). We estimated cause-specific hazards ratios for the association of covariates with PHF and non-PHF. There were 1,728 incident HF events in the primary analysis: 168 (10%) classified as PHF, 1,526 (88%) as non-PHF, and 34 unclassified (2%). For those 1,045 participants in whom LV ejection fraction was known at the time of the HF event, it was ≥45% in 89 of 118 participants (75%) with PHF, compared to 517 of 927 participants (55%) with non-PHF (p0.001). Increased age, male gender, diabetes, and angina at baseline were associated with both PHF and non-PHF (range of hazard ratios (HR): 1.04-2.05]. Being Black was inversely associated with PHF [HR: 0.46, 95% confidence interval: 0.25-0.86]. Participants with increased age, without baseline angina, and with baseline LVEF55% were at a significantly lower risk for PHF compared to non-PHF. Among those with PHF, surgical procedures-including cardiac, orthopedic, gastrointestinal, vascular, and urologic-comprised 83.3%, while percutaneous procedures comprised 8.9% (including 6.5% represented by cardiac catheterizations and pacemaker placements). Another group composed of a variety of procedures commonly requiring large fluid volume administration comprised 7.7%. There was a lower all-cause 30-day mortality in the PHF versus the non-PHF group (2.2% vs 5.7%), with a nonsignificant odds ratio of 0.39 in a minimally adjusted model. When individuals with prior myocardial infarction (MI) were excluded in a sensitivity analysis, the proportion of incident HF with concurrent MI was greater for PHF (32.9%) than for non-PHF (19.8%). In conclusion, PHF in older adults is a common entity with relatively low 30-day mortality. Baseline angina, lower age, and LVEF ≥ 55% were associated with a higher risk of PHF compared to non-PHF. Being Black was associated with a lower risk of PHF and PHF as a proportion of HF was lower in Black than in non-Black participants. Compared to non-PHF, PHF more frequently presented with concurrent MI and with preserved LV ejection fraction.

Objective This study examined the short- and long-term effects of adding caloric restriction to 5 months of aerobic exercise training on executive function in sedentary older adults with obesity. Methods Sedentary adults with obesity aged 65 to 79 years completed a randomized trial investigating the cardiorespiratory benefits of adding moderate (~ 250 kcal) or high (~ 600 kcal) caloric restriction to a 20-week aerobic exercise program. Approximately half (n = 88) completed a cognitive assessment battery at baseline, post intervention, and 18 to 24 months after intervention completion. The primary outcome was an executive function composite score. Results In the overall sample, the executive function composite increased 0.114 from baseline to postintervention (P = 0.01). Randomization to caloric restriction did not significantly alter executive function over aerobic exercise alone, nor were there between-group differences on any individual executive function test following the intervention or at long-term follow-up. Adding caloric restriction to exercise was associated with a modest increase in Mini-Mental State Examination score (P = 0.04). In the overall sample, increases from baseline at long-term follow-up were noted in digit symbol and word list recall performance as well. Conclusions Adding caloric restriction to a 20-week aerobic exercise program does not worsen or improve executive function more than exercise alone assessed up to 24 months post randomization.

BACKGROUND: Dietary protein and micronutrients are important to the maintenance of bone health and may be an effective countermeasure to weight-loss–associated bone loss. OBJECTIVES: We aimed to determine the effect of a 6-mo hypocaloric, nutritionally complete, higher-protein meal plan on change in bone density and quality as compared with weight stability in older adults using a randomized post-test design. We hypothesized that participants randomly assigned to this meal plan would maintain similar bone density and quality to weight-stable controls, despite significant reductions in body mass. METHODS: Ninety-six older adults (aged 70.3 ± 3.7 y, 74% women, 27% African American) with obesity [body mass index (kg/m(2)): 35.4 ± 3.3] were randomly assigned to a 6-mo hypocaloric, nutritionally complete, higher-protein meal plan targeting ≥1.0 g protein · kg body weight(–1) · d(–1) [weight-loss (WL) group; n = 47] or to a weight-stability (WS) group targeting 0.8 g protein · kg body weight(–1) · d(–1), the current Recommended Dietary Allowance (n = 49). The primary outcome was total hip bone mineral density (BMD), with femoral neck BMD, lumbar spine BMD, and lumbar spine trabecular bone score (TBS) as secondary outcomes, all assessed at baseline and 3 and 6 mo with dual-energy X-ray absorptiometry. RESULTS: Baseline total hip, femoral neck, and lumbar spine BMDs were 1.016 ± 0.160, 0.941 ± 0.142, and 1.287 ± 0.246 g/cm(2), respectively; lumbar TBS was 1.398 ± 0.109. Despite significant weight loss achieved in the WL group (6.6 ± 0.4 kg; 8.6% ± 0.4% of baseline weight), 6-mo regional BMD estimates were similar to those in the WS group (all P > 0.05). Lumbar spine TBS significantly increased at 6 mo in the WL group (mean: 1.421; 95% CI: 1.401, 1.441) compared with the WS group (1.390: 95% CI: 1.370, 1.409; P = 0.02). CONCLUSIONS: Older adults following a hypocaloric, nutritionally complete, higher-protein meal plan maintained similar bone density and quality to weight-stable controls. Our data suggest that adherence to this diet does not produce loss of hip and spine bone density in older adults and may improve bone quality. This trial was registered at clinicaltrials.gov as NCT02730988.

Importance Thigh muscle weakness is associated with knee discomfort and osteoarthritis disease progression. Little is known about the efficacy of high-intensity strength training in patients with knee osteoarthritis or whether it may worsen knee symptoms. Objective To determine whether high-intensity strength training reduces knee pain and knee joint compressive forces more than low-intensity strength training and more than attention control in patients with knee osteoarthritis. Design, Setting, and Participants Assessor-blinded randomized clinical trial conducted at a university research center in North Carolina that included 377 community-dwelling adults (≥50 years) with body mass index (BMI) ranging from 20 to 45 and with knee pain and radiographic knee osteoarthritis. Enrollment occurred between July 2012 and February 2016, and follow-up was completed September 2017. Interventions Participants were randomized to high-intensity strength training (n = 127), low-intensity strength training (n = 126), or attention control (n = 124). Main Outcomes and Measures Primary outcomes at the 18-month follow-up were Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) knee pain (0 best-20 worst; minimally clinically important difference [MCID, 2]) and knee joint compressive force, defined as the maximal tibiofemoral contact force exerted along the long axis of the tibia during walking (MCID, unknown). Results Among 377 randomized participants (mean age, 65 years; 151 women [40%]), 320 (85%) completed the trial. Mean adjusted (sex, baseline BMI, baseline outcome values) WOMAC pain scores at the 18-month follow-up were not statistically significantly different between the high-intensity group and the control group (5.1 vs 4.9; adjusted difference, 0.2; 95% CI, −0.6 to 1.1;P = .61) or between the high-intensity and low-intensity groups (5.1 vs 4.4; adjusted difference, 0.7; 95% CI, −0.1 to 1.6;P = .08). Mean knee joint compressive forces were not statistically significantly different between the high-intensity group and the control group (2453 N vs 2512 N; adjusted difference, −58; 95% CI, −282 to 165 N;P = .61), or between the high-intensity and low-intensity groups (2453 N vs 2475 N; adjusted difference, −21; 95% CI, −235 to 193 N;P = .85). There were 87 nonserious adverse events (high-intensity, 53; low-intensity, 30; control, 4) and 13 serious adverse events unrelated to the study (high-intensity, 5; low-intensity, 3; control, 5). Conclusions and Relevance Among patients with knee osteoarthritis, high-intensity strength training compared with low-intensity strength training or an attention control did not significantly reduce knee pain or knee joint compressive forces at 18 months. The findings do not support the use of high-intensity strength training over low-intensity strength training or an attention control in adults with knee osteoarthritis. Trial Registration ClinicalTrials.gov Identifier:NCT01489462

Randomized, controlled trials (RCTs) show intentional weight loss improves body composition and physical function in older adults; however, the long-term benefits (and risks) are unknown. We conducted a pilot study to assess the feasibility of recalling prior RCT participants to examine the long-term effects of intentional weight loss on body composition and physical function. A weighted, random sample of 60 older adults who were randomized to caloric restriction plus exercise (CR + EX) or exercise (EX) only in 5 prior RCTs (mean age at randomization, 67.3 years; 69% women, 80% white) were invited to participate. Follow-up was obtained on 89% (42 clinic visits, 10 phone interviews, 1 death) an average of 3.5 years (range, 2.2-5.8 years) after RCT completion. Despite greater weight, fat and lean mass loss during the RCT (mean difference in change (95% CI): -4.19 (-7.52, -0.86), -2.75 (-5.10, -0.40), and -2.32 (-3.69, -0.95) kg, respectively) in those randomized to CR + EX, long-term changes in weight (2.05 (-2.35, 6.45) kg) and body composition (1.80 (-1.56, 5.17) and 0.03 (-2.20, 2.26) kg for fat and lean mass, respectively) from baseline and physical function at long-term follow-up (mean difference in 400-m walk and SPPB (95% CI): 23.2 (-19.3, 65.6) sec and -0.03 (-1.02, 0.96) points, respectively) were similar in CR + EX and EX only. Although improvements in weight and body composition following intentional weight loss may not be sustained long-term, physical function does not appear to be negatively impacted. A larger study is needed to confirm these results.

Background FABP‐4 (fatty acid binding protein‐4) is a lipid chaperone in adipocytes and has been associated with prognosis in selected clinical populations. We investigated the associations between circulating FABP ‐4, risk of incident cardiovascular disease ( CVD ), and risk of CVD mortality among older adults with and without established CVD . Methods and Results In the Cardiovascular Health Study, we measured FABP 4 levels in stored specimens from the 1992–993 visit and followed participants for incident CVD if they were free of prevalent CVD at baseline and for CVD mortality through June 2015. We used Cox regression to estimate hazard ratios for incident CVD and CVD mortality per doubling in serum FABP ‐4 adjusted for age, sex, race, field center, waist circumference, blood pressure, lipids, fasting glucose, and C‐reactive protein. Among 4026 participants free of CVD and 681 with prevalent CVD , we documented 1878 cases of incident CVD and 331 CVD deaths, respectively. In adjusted analyses, FABP ‐4 was modestly associated with risk of incident CVD (mean, 34.24; SD , 18.90; HR , 1.10 per doubling in FABP ‐4, 95% CI , 1.00–1.21). In contrast, FABP ‐4 was more clearly associated with risk of CVD mortality among participants without ( HR hazard ratio 1.24, 95% CI , 1.10–1.40) or with prevalent CVD ( HR hazard ratio 1.57, 95% CI , 1.24–1.98). These associations were not significantly modified by sex, age, and waist circumference. Conclusions Serum FABP ‐4 is modestly associated with risk of incident CVD even after adjustment for standard risk factors, but more strongly associated with CVD mortality among older adults with and without established CVD .

Background Adiposity-related ventilatory constraints in older adults can potentially contribute to greater risk of exercise intolerance and mobility disability. This study investigated whether ventilatory limitation, measured by breathing reserve (BR) at peak exercise, is associated with body composition and physical function in older adults with obesity. Methods This study was a cross-sectional analysis of data from a community-based cohort (N = 177) of older men and women (65–79 years) with obesity (body mass index = 30–45 kg/m2). All participants underwent cardiopulmonary exercise testing on a treadmill, dual-energy X-ray absorptiometry for body composition, and physical function assessments. We examined relationships between BR and body composition and physical function using multiple linear regression and compared a subset with (BR ≤ 30%; BR-low; n = 56) and without (BR ≥ 45%; BR-high, n = 48) ventilatory limitation using unpaired Student’s t test and analysis of covariance. Results BR was inversely related to total body mass, lean mass, fat mass, % body fat, and waist circumference (p < 0.05 for all). BR was positively related to 400 m walk time (p = .006) and inversely related to usual gait speed (p = .05) and VO2peak (p < .0001), indicative of worse physical function. BR-low had greater adiposity, but also greater lean mass, higher VO2peak, and faster 400 m walk time, compared to BR-high (p < .05, for all). Conclusions Older adults with obesity who also have ventilatory limitation have overall higher measures of adiposity, but do not have lower peak exercise capacity or physical function. Thus, ventilatory limitation does not appear to be a contributing factor to obesity-related decrements in exercise tolerance or mobility.

Objectives To investigate glucose levels as a risk factor for unrecognized myocardial infarctions (UMIs). Design Cohort Setting Cardiovascular Health Study. Participants Individuals aged 65 and older with fasting glucose measurements (N=4,355; normal fasting glucose (NFG), n = 2,041; impaired fasting glucose (IFG), n = 1,706; DM: n = 608; 40% male, 84% white, mean age 72.4 ± 5.6). Measurements The relationship between glucose levels and UMI was examined. Participants with prior coronary heart disease (CHD) or UMI on initial electrocardiography were excluded. Using Minnesota codes, UMI was identified according to the presence of pathological Q‐waves or minor Q‐waves with ST‐T abnormalities. Crude and adjusted hazard ratios (HRs) were calculated. Analyses were adjusted for age, sex, body mass index (BMI), hypertension, antihypertensive and lipid‐lowering medication use, total cholesterol, high‐density lipoprotein cholesterol, and smoking status. Results Over a mean follow‐up of 6 years, there were 459 incident UMIs (NFG, n=202; IFG, n=183; DM, n=74). Participants with IFG were slightly more likely than those with NFG to experience a UMI (hazard ratio (HR)=1.11, 95% confidence interval (CI)=0.91–1.36, p = .30), and those with DM were more likely than those with NFG to experience a UMI (HR=1.65, 95% CI=1.25–2.13, p

Summary Objective Weight loss has beneficial effects on clinical outcomes in knee osteoarthritis (OA), but the mechanism is still unclear. Since meniscus extrusion is associated with knee pain, this study assessed whether weight loss by diet and/or exercise is associated with less progression in meniscus extrusion measures over time. Design The Intensive Diet and Exercise for Arthritis trial (IDEA) was a prospective, single-blind, randomized-controlled trial including overweight and obese older adults with knee pain and radiographic OA. Participants were randomized to 18-month interventions: exercise only, diet only or diet + exercise. In a random subsample of 105 participants, MRIs were obtained at baseline and follow-up. The medial and lateral menisci were segmented and quantitative position and size measures were obtained, along with semiquantitative extrusion measures. Linear and log-binomial regression were used to examine the association between change in weight and change in meniscus measures. Between-group differences were analyzed using an analysis of covariance. Results Weight loss was associated with less progression over time of medial meniscus extrusion as measured by the maximum (β: −24.59 μm, 95%CI: −41.86, −7.33) and mean (β: −19.08 μm, 95%CI: −36.47, −1.70) extrusion distances. No relationships with weight loss were observed for lateral meniscus position, medial or lateral meniscus size or semiquantitative measures. Change in meniscus position and size did not differ significantly between groups. Conclusions Weight loss was associated with beneficial modifications of medial meniscus extrusion over 18 months. This may be one of the mechanisms by which weight loss translates into a clinical benefit. Clinical trial registration NCT00381290.

Background and aims Understanding contributions of lean and fat tissue to cardiovascular and non-cardiovascular mortality may help clarify areas of prevention in older adults. We aimed to define distributions of lean and fat tissue in older adults and their contributions to cause-specific mortality. Methods and results A total of 1335 participants of the Cardiovascular Health Study (CHS) who underwent dual-energy x-ray absorptiometry (DEXA) scans were included. We used principal components analysis (PCA) to define two independent sources of variation in DEXA-derived body composition, corresponding to principal components composed of lean ("lean PC") and fat ("fat PC") tissue. We used Cox proportional hazards regression using these PCs to investigate the relationship between body composition with cardiovascular and non-cardiovascular mortality. Mean age was 76.2 ± 4.8 years (56% women) with mean body mass index 27.1 ± 4.4 kg/m 2 . A greater lean PC was associated with lower all-cause (HR = 0.91, 95% CI 0.84–0.98, P = 0.01) and cardiovascular mortality (HR = 0.84, 95% CI 0.74–0.95, P = 0.005). The lowest quartile of the fat PC (least adiposity) was associated with a greater hazard of all-cause mortality (HR = 1.24, 95% CI 1.04–1.48, P = 0.02) relative to fat PCs between the 25th–75th percentile, but the highest quartile did not have a significantly greater hazard (P = 0.70). Conclusion Greater lean tissue mass is associated with improved cardiovascular and overall mortality in the elderly. The lowest levels of fat tissue mass are linked with adverse prognosis, but the highest levels show no significant mortality protection. Prevention efforts in the elderly frail may be best targeted toward improvements in lean muscle mass.

BACKGROUND: Little is known about the comparative effect of aerobic training (AT) versus resistance training (RT) on gait speed, a strong predictor of disability. AIMS: To compare the effect of AT versus RT on gait speed and other functional measures. METHODS: Overweight and obese [body mass index (BMI) ≥27.0 kg/m(2)] sedentary men and women aged 65–79 years engaged in 5 months of either 4 days/weeks moderate-intensity treadmill walking, AT, (n = 44) or 3 days/weeks moderate-intensity RT (n = 56). Usual-pace gait speed, fast-pace gait speed and short physical performance battery (SPPB) were evaluated in all participants before and after training. Peak oxygen consumption (VO(2)peak) was assessed in AT participants only, and knee extensor strength was assessed in RT participants. RESULTS: Both AT and RT resulted in clinically significant improvements in usual-pace gait speed (0.08 ± 0.14 and 0.08 ± 0.17 m/s, respectively, both p < 0.05) and SPPB (0.53 ± 1.40 and 0.53 ± 1.20 points, both p < 0.05) and chair rise time (−1.2 ± 3.2 and −1.7 ± 3.0 s, p < 0.05). Only AT improved fast-pace gait speed (0.11 ± 0.10 m/s, p < 0.05). In the RT participants, lower baseline knee strength was associated with less improvement in usual-pace gait speed. In AT participants, lower baseline VO(2)peak was associated with less improvement in chair rise time and self-reported disability. DISCUSSION: While both AT and RT improved usual-pace gait speed, only AT improved fast-pace gait speed. Lower baseline fitness was associated with less improvement with training. CONCLUSION: Research to directly compare which mode of training elicits the maximum improvement in older individuals with specific functional deficits could lead to better intervention targeting.

BACKGROUND: Obesity compounds aging-related declines in cardiorespiratory fitness, with accompanying fatigue and disability. This study determined the effects of two different levels of caloric restriction (CR) during aerobic training on cardiorespiratory fitness, fatigue, physical function, and cardiometabolic risk. METHODS: The INFINITE study was a 20-week randomized trial in 180 older (65–79 years) men and women with obesity (body mass index = 30–45 kg/m2). Participants were randomly assigned to (i) aerobic training (EX; treadmill 4 days/wk for 30 minutes at 65%–70% of heart rate reserve), (ii) EX with moderate (−250 kcal/d) CR (EX + Mod-CR), or (iii) EX with more intensive (−600 kcal/d) CR (EX + High-CR). Cardiorespiratory fitness (peak aerobic capacity, VO(2) peak, primary outcome) was determined during a graded exercise test. RESULTS: One hundred and fifty-five participants returned for 20-week data collection (87% retention). VO(2) peak increased by 7.7% with EX, by 13.8% with EX + Mod-CR, and by 16.0% with EX + High-CR, and there was a significant treatment effect (EX + High-CR = 21.5 mL/kg/min, 95% confidence interval = 19.8–23.2; EX + Mod-CR = 21.2 mL/kg/min, 95% confidence interval = 19.4–23.0; EX = 20.1 mL/kg/min, 95% confidence interval = 18.4–21.9). Both CR groups exhibited significantly greater improvement in self-reported fatigue and disability and in glucose control, compared with EX. CONCLUSION: Combining aerobic exercise with even moderate CR is more efficacious for improving cardiorespiratory fitness, fatigue and disability, and glucose control than exercise alone and is as effective as higher-dose CR.

Physical activity decreases the risk of osteoarthritis (OA)-related disability; however, pain and lack of confidence represent barriers for older adults with knee OA. The purpose of this study was to examine (a) the baseline associations among self-efficacy and physical activity, function, and pain; (b) longitudinal changes in self-efficacy; and (c) whether self-efficacy mediates treatment effects on clinical outcomes. The Intensive Diet and Exercise for Arthritis (IDEA) trial was a single-blind, randomized controlled 18-month study including 454 overweight/obese older adults (M age = 66 years) with knee OA. Participants were randomized to one of three interventions: exercise (E), diet-induced weight loss (D), or both (D+E). Self-efficacy for gait, balance, and walking duration were assessed at baseline, 6 months, and 18 months. Baseline associations were tested using Pearson correlations, and group least squares means were compared using mixed linear models at follow-up. Participants with higher self-efficacy reported significantly better physical function and less knee pain at baseline, walked farther (6-min walk), and were more physically active (all |r| > 0.12, all p < .01). Significant differences between groups were detected for all self-efficacy measures at 18 months; the D+E group reported significantly (all p < .005) higher self-efficacy for gait, walking duration, and balance compared with the D- or E-only groups. Self-efficacy significantly (p < .05) mediated treatment effects on physical function and pain at 18 months. A combined intervention of diet-induced weight loss and exercise is the treatment of choice to maximize self-efficacy, improve physical function, and reduce pain in overweight/obese adults with knee OA.

Promoting lasting weight loss among older adults is an important public health challenge. Participation in physical activity aids in weight loss and is important for the maintenance of physical function and quality of life. However, traditional intensive lifestyle interventions place a focus on discrete bouts of structured activity, leaving much of the remainder of the day for sedentary behavior. Structured exercise and weight loss programs often produce short-term weight loss that is typically followed by weight regain, and older adults are more likely to regain weight as fat mass rather than lean mass. Preliminary evidence suggests a focus on day-long movement intended to minimize time spent sitting produces better short-term weight loss and weight maintenance. Herein we describe the design and methods for a three-arm randomized controlled trial comparing mHealth-supported weight loss (WL) + structured exercise (EX); WL + a novel daily movement intervention (SitLess); and WL + EX + SitLess. Older adults (N = 180) will be randomly assigned to one of the three interventions, each comprised of a 6-month intensive phase; a 3-month transition phase; and a 9-month maintenance phase. The primary aim of the study is to determine whether the addition of SitLess to a traditional intensive lifestyle intervention comprised of dietary weight loss and structured exercise produces a larger 18-month reduction in body weight relative to WL + EX and WL + SitLess.

Declining mobility is associated with increased accumulation of white matter hyperintensities (WMH). However, a high WMH burden is not always accompanied by impaired mobility. Our previous work demonstrates that some variance in mobility may be explained by brain network connectivity. Here, we extended this work by measuring WMHs and brain networks in older adults participating in a lifestyle intervention. The Short Physical Performance Battery (SPPB) and resting state functional magnetic resonance imaging (fMRI) were collected before and after a 5-month caloric restriction plus aerobic exercise intervention in 57 obese, sedentary adults aged 65-78. Participants were categorized based on median splits of baseline SPPB scores and WMH burden: Expected Healthy (EH: low WMH, SPPB≥11, n=16), Expected Impaired (EI: high WMH, SPPB≤10, n=17), Unexpected Healthy (UH: high WMH, SPPB≥11, n=12), and Unexpected Impaired (UI: low WMH, SPPB≤10, n=12). Graph theory-based methods were used to characterize brain networks and compare the four groups. At baseline, the somatomotor cortex community structure (SMC-CS) was less consistent in EI (p=0.05) and UI (p=0.23) compared to EH. The EI (mean=1.25, p=0.003) and UI (mean=1.57, p=0.001) significantly improved their SPPB scores following the intervention. Although both groups had equivalent SPPB scores, SMC-CS was less consistent in the UH than EH (p=0.16). However, UH displayed a significant (p=0.004) increase in second-order connections to the precuneus compared to EH. These data suggest that studying brain networks could improve the understanding of the development of mobility disability and the CNS contributions to mobility independent of white matter disease.

Summary Purpose Report the radiographic and magnetic resonance imaging (MRI) structural outcomes of an 18-month study of diet-induced weight loss, with or without exercise, compared to exercise alone in older, overweight and obese adults with symptomatic knee osteoarthritis (OA). Methods Prospective, single-blind, randomized controlled trial that enrolled 454 overweight and obese (body mass index, BMI = 27–41 kg m −2 ) older (age ≥ 55 yrs) adults with knee pain and radiographic evidence of femorotibial OA. Participants were randomized to one of three 18-month interventions: diet-induced weight loss only (D); diet-induced weight loss plus exercise (D + E); or exercise-only control (E). X-rays ( N = 325) and MRIs ( N = 105) were acquired at baseline and 18 months follow-up. X-ray and MRI (cartilage thickness and semi-quantitative (SQ)) results were analyzed to compare change between groups at 18-month follow-up using analysis of covariance (ANCOVA) adjusted for baseline values, baseline BMI, and gender. Results Mean baseline descriptive characteristics of the cohort included: age, 65.6 yrs; BMI 33.6 kg m −2 ; 72% female; 81% white. There was no significant difference between groups in joint space width (JSW) loss; D −0.07 (SE 0.22) mm, D + E −0.27 (SE 0.22) mm and E −0.16 (SE 0.24) mm ( P = 0.79). There was also no significant difference in MRI cartilage loss between groups; D −0.10(0.05) mm, D + E −0.13(0.04) mm and E −0.05(0.04) mm ( P = 0.42). Conclusion Despite the potent effects of weight loss in this study on symptoms as well as mechanistic outcomes (such as joint compressive force and markers of inflammation), there was no statistically significant difference between the three active interventions on the rate of structural progression either on X-ray or MRI over 18-months.

Background: Resistance training (RT) improves muscle strength and overall physical function in older adults. RT may be particularly important in the obese elderly who have compromised muscle function. Whether caloric restriction (CR) acts synergistically with RT to enhance function is unknown. Objective: As the primary goal of the Improving Muscle for Functional Independence Trial (I’M FIT), we determined the effects of adding CR for weight loss on muscle and physical function responses to RT in older overweight and obese adults. Design: I’M FITwas a 5-mo trial in 126 older (65–79 y) overweight and obese men and women who were randomly assigned to a progressive, 3-d/wk, moderate-intensity RT intervention with a weightloss intervention (RT+CR) or without a weight-loss intervention (RT). The primary outcome was maximal knee extensor strength; secondary outcomes were muscle power and quality, overall physical function, and total body and thigh compositions. Results: Body mass decreased in the RT+CR group but not in the RT group. Fat mass, percentage of fat, and all thigh fat volumes decreased in both groups, but only the RT+CR group lost lean mass. Adjusted postintervention body- and thigh-composition measures were all lower with RT+CR except intermuscular adipose tissue (IMAT). Knee strength, power, and quality and the 4-m gait speed increased similarly in both groups. Adjusted postintervention means for a 400-m walk time and self-reported disability were better with RT+CR with no group differences in other functional measures, including knee strength. Participants with a lower percentage of fat and IMAT at baseline exhibited a greater improvement in the 400-m walk and knee strength and power. Conclusions: RT improved body composition (including reducing IMAT) and muscle strength and physical function in obese elderly, but those with higher initial adiposity experienced less improvement. The addition of CR during RT improves mobility and does not compromise other functional adaptations to RT. These findings support the incorporation of RT into obesity treatments for this population regardless of whether CR is part of the treatment. This trial was registered at clinicaltrials. gov as NCT01049698. Am J Clin Nutr 2015;101:991–9.

Summary Objective Quadriceps muscle weakness is common in knee osteoarthritis (OA). While pain, disuse, and atrophy are commonly cited causes for muscle weakness in OA, emerging evidence suggests changes in muscle quality also occur. Alterations in muscle quality are not well understood, but likely include both cellular and morphologic adaptions. The purpose of this study was to conduct the first cellular-level analysis of the vastus lateralis in adults with moderate knee OA. Methods Vastus lateralis biopsies were obtained from 24 subjects with moderate knee OA and 15 healthy controls. Quadriceps strength, muscle fiber cross sectional area (CSA), fiber type distribution, extracellular matrix (ECM) content, satellite cell abundance, and profibrotic gene expression were assessed. Results Relative to controls, quadriceps strength was significantly lower in OA subjects (OA 62.23, 50.67–73.8 Nm vs 91.46, 75.91–107.0 Nm, P = 0.003) despite no difference in fiber CSA. OA subjects had significantly fewer Type I fibers (OA 41.51, 35.56–47.47% vs 53.07, 44.86–61.29%, P = 0.022) and more hybrid IIa/x fibers (OA 24.61, 20.61–28.61% vs 16.4, 11.60–21.20%, P = 0.009). Significantly greater ECM content, lower satellite cell density, and higher profibrotic gene expression was observed with OA, and muscle collagen content was inversely correlated to strength and satellite cell (SC) density. Conclusion Lower quadriceps function with moderate OA may not result from fiber size impairments, but is associated with ECM expansion. Impaired satellite cell density, high profibrotic gene expression, and a slow-to-fast fiber type transition may contribute to reduced muscle quality in OA. These findings can help guide therapeutic interventions to enhance muscle function with OA.

It is well established that aging-related changes in brain structure such as white matter lesions and atrophy are linked with changes in gait and mobility. However, changes in neural function may precede irreversible changes in brain structure. Previous work has shown that functional brain networks are associated with mobility function in older adults. Here, we sought to extend that work by replicating previous associations between mobility function and brain networks, and testing whether improving mobility through an exercise intervention produced concomitant improvements in brain networks. Short Physical Performance Battery (SPPB) and resting state functional magnetic resonance imaging (fMRI) were collected in 66 obese, sedentary adults 65–80 years old before and after a randomized trial adding weight loss to a 5-month aerobic exercise intervention. Graph theory-based methods were used to characterize brain network organization and compare participants in the highest (SPPB=12, n=22) and lowest (SPPB=3–9, n=21) tertiles of SPPB score. We replicated findings that the community structure of somatomotor cortex was less consistent in the Low SPPB group compared to the High SPPB group (p=0.15). The Low SPPB group improved SPPB significantly after the intervention (mean=1.73, 95%CI [1.02–2.45], p

The prevalence of metabolic syndrome (MetS) is greatest in older obese adults, and effective evidence-based treatment strategies are lacking. This study determined the efficacy of adding caloric restriction (CR) for weight loss to resistance training (RT) on MetS and its individual components in older overweight and obese adults.We performed a 5-month randomized controlled trial in 126 older (65-79 yr) overweight and obese (body mass index = 27-35 kg·m) men and women who were assigned to a progressive 3-d·wk moderate-intensity RT with (RT + CR) or without caloric restriction (RT). MetS components, according to the National Cholesterol Education Program Adult Treatment Panel III, were determined before and immediately after the interventions.Body mass decreased in RT + CR (-5.67% loss of initial mass) but was unchanged in RT (-0.15%). Compared with RT, RT + CR resulted in reduced VLDL cholesterol, triglycerides, and systolic and diastolic blood pressures (P between 0.000 and 0.013). The RT group showed no significant within-group changes in MetS criteria. Abdominal obesity, hypertension, the number of metabolic abnormalities and the presence of MetS significantly decreased with RT + CR. There were significant group differences for abdominal obesity, hypertension, and number of metabolic abnormalities.RT + CR is an effective strategy for improving some of the metabolic abnormalities associated with MetS among older overweight and obese adults.

Recently, we determined that in a rigorously monitored environment an intensive diet-induced weight loss of 10% combined with exercise was significantly more effective at reducing pain in men and women with symptomatic knee osteoarthritis (OA) than either intervention alone. Compared to previous long-term weight loss and exercise trials of knee OA, our intensive diet-induced weight loss and exercise intervention was twice as effective at reducing pain intensity. Whether these results can be generalized to less intensively monitored cohorts is unknown. Thus, the policy relevant and clinically important question is: Can we adapt this successful solution to a pervasive public health problem in real-world clinical and community settings? This study aims to develop a systematic, practical, cost-effective diet-induced weight loss and exercise intervention implemented in community settings and to determine its effectiveness in reducing pain and improving other clinical outcomes in persons with knee OA. This is a Phase III, pragmatic, assessor-blinded, randomized controlled trial. Participants will include 820 ambulatory, community-dwelling, overweight and obese (BMI ≥ 27 kg/m2) men and women aged ≥ 50 years who meet the American College of Rheumatology clinical criteria for knee OA. The primary aim is to determine whether a community-based 18-month diet-induced weight loss and exercise intervention based on social cognitive theory and implemented in three North Carolina counties with diverse residential (from urban to rural) and socioeconomic composition significantly decreases knee pain in overweight and obese adults with knee OA relative to a nutrition and health attention control group. Secondary aims will determine whether this intervention improves self-reported function, health-related quality of life, mobility, and is cost-effective. Many physicians who treat people with knee OA have no practical means to implement weight loss and exercise treatments as recommended by numerous OA treatment guidelines. This study will establish the effectiveness of a community program that will serve as a blueprint and exemplar for clinicians and public health officials in urban and rural communities to implement a diet-induced weight loss and exercise program designed to reduce knee pain and improve other clinical outcomes in overweight and obese adults with knee OA. clinicaltrials.gov Identifier: NCT02577549 October 12, 2015.

The Intensive Diet and Exercise for Arthritis (IDEA) trial was an 18-month randomized controlled trial that enrolled 454 overweight and obese older adults with symptomatic and radiographic knee osteoarthritis (OA). Participants were randomized to either exercise (E), intensive diet-induced weight loss (D), or intensive diet-induced weight loss plus exercise (D + E) interventions. We previously reported that the clinical benefits of D + E were significantly greater than with either intervention alone (e.g., greater pain reduction, and better function, mobility, and health-related quality of life). We now test the hypothesis that D + E has greater overall benefit on gait mechanics compared to either intervention alone. Knee joint loading was analyzed using inverse dynamics and musculoskeletal modeling. Analysis of covariance determined the interventions’ effects on gait. The D + E group walked significantly faster at 18-month follow-up (1.35 m s(−1)) than E (1.29 m s(−1), p = 0.0004) and D (1.31 m s(−1), p = 0.0007). Tibiofemoral compressive impulse was significantly lower (p = 0.0007) in D (1069 N s) and D + E (1054 N s) compared to E (1130 N s). D had significantly lower peak hip external rotation moment (p = 0.01), hip abduction moment (p = 0.0003), and peak hip power production (p = 0.016) compared with E. Peak ankle plantar flexion moment was significantly less (p < 0.0001) in the two diet groups compared with E. There also was a significant dose-response to weight loss; participants that lost >10% of baseline body weight had significantly (p = 0.0001) lower resultant knee forces and lower muscle (quadriceps, hamstring, and gastrocnemius) forces than participants that had less weight loss. Compared to E, D produces significant load reductions at the hip, knee, and ankle; combining D with E attenuates these reductions, but most remain significantly better than with E alone.

Objective To compare the regional differences in subcutaneous adipose tissue hormone/cytokine production in abdominally obese women during weight loss. Methods Forty-two abdominally obese, older women underwent a 20-week weight loss intervention composed of hypocaloric diet with or without aerobic exercise (total energy expenditure: ∼2800 kcal/week). Subcutaneous (gluteal and abdominal) adipose tissue biopsies were conducted before and after the intervention. Adipose tissue gene expression and release of leptin, adiponectin, and interleukin 6 (IL-6) were determined. Results The intervention resulted in significant weight loss (−10.1 ± 0.7 kg, P < 0.001). At baseline, gene expression of adiponectin were higher (P < 0.01), and gene expression and release of IL-6 were lower (both P < 0.05) in abdominal than in gluteal adipose tissue. After intervention, leptin gene expression and release were lower in both gluteal and abdominal adipose tissue compared to baseline (P < 0.05-0.01). Abdominal, but not gluteal, adipose tissue adiponectin gene expression and release increased after intervention (both P < 0.05). Conclusion A 20-week weight loss program decreased leptin production in both gluteal and abdominal adipose tissue, but only increased adiponectin production from abdominal adipose tissue in obese women. This depot-specific effect may be of importance for the treatment of health complications associated with abdominal adiposity.

OVERWEIGHT and obesity are associated with a wide range of diseases (1) and constitute one of the most prevalent and disabling problems among older adults in the United States (2). Obese persons have poorer relative strength, an increased risk for mobility limitations, and increased risk of impaired physical function, all of which contribute to a higher risk for institutionalization and death (3–5). In spite of this, whether or not overweight or obese older adults should engage in “intentional” weight loss is controversial (6–8). One concern is that while voluntary weight loss reduces fat mass, it also reduces lean body mass (LBM), which may lead to impairments in muscle strength and power, resulting in limitations in physical function (9,10). Therefore, a strong rationale exists for incorporating resistance exercise in weight loss interventions for overweight or obese older adults (11,12). Currently, there are limited data on the effect of weight loss combined with resistance training (RT) on changes in LBM and muscle strength and power in this population. Fat infiltration in muscle has been associated with reduced strength and lower extremity function and with increased risk of mobility loss in older men and women (13,14). Pioglitazone, a peroxisome proliferator-activated receptor (PPAR)-γ agonist used in treating type 2 diabetes (T2D) appears to change the distribution of fat within the body, resulting in a significant decrease in the visceral-to-subcutaneous fat ratio (15). Interestingly, pioglitazone has also been shown to decrease intramyocellular lipid content in individuals with T2D (16,17). Therefore, treatment with pioglitazone may be a novel approach to preserve or improve muscle function in older adults undergoing weight loss treatment. Whether or not it may work synergistically with resistance exercise to augment increases in muscle strength and power has not been studied. We examined the effects of RT and/or pioglitazone treatment on muscle power and strength in overweight or obese older women and men without T2D undergoing voluntary weight loss via caloric restriction. This is a secondary data analysis from a study designed to examine two differing strategies for affecting two different tissue compartments during weight loss: RT to reduce lean mass loss and pioglitazone to accelerate visceral fat loss (18).

To examine the effect of exercise modality during weight loss on hip and spine bone mineral density (BMD) in overweight and obese, older adults.This analysis compared data from two 5-month, randomized controlled trials of caloric restriction (CR; inducing 5-10% weight loss) with either resistance training (RT) or aerobic training (AT) in overweight and obese, older adults. Participants in the RT + CR study underwent 3 days/week of 8 upper/lower body exercises (3 sets, 10 repetitions at 70% 1 RM) and participants in the AT+CR study underwent 4 days/week of treadmill walking (30 min at 65-70% heart rate reserve). BMD at the total hip, femoral neck, and lumbar spine was assessed via dual-energy X-ray absorptiometry at baseline and 5 months.A total of 123 adults (69.4 ± 3.5 years, 67% female, 81% Caucasian) participated in the RT+CR (n = 60) and AT+CR (n = 63) interventions. Average weight loss was 5.7% (95% CI: 4.6-6.7%) and 8.2% (95% CI: 7.2-9.3%) in RT+CR and AT+CR groups, respectively. After adjustment for age, gender, race, baseline BMI and BMD, and weight change, differential treatment effects were observed for total hip and femoral neck (both p.05), but not lumbar spine. Total hip (1.83 [-3.90, 7.55] mg/cm2) and femoral neck (9.14 [-0.70, 18.98] mg/cm2) BMD was unchanged in RT+CR participants, and modestly decreased in AT+CR participants (total hip: -7.01 [-12.73, -1.29] mg/cm2; femoral neck: -5.36 [-14.92, 4.20] mg/cm2).Results suggest performing resistance, rather than aerobic, training during CR may attenuate loss of hip and femoral neck BMD in overweight and obese older adults. Findings warrant replication from a long-term, adequately powered, RCT.

OVERWEIGHT and obesity are significant public health problems, with recent estimates suggesting that 72.3% and 64.1% of adult men and women, respectively, have a body mass index (BMI) greater than or equal to 25kg/m2 (1). In women, postmenopausal status is associated with higher prevalence of overweight and obesity (2). Excessive body weight often predisposes to chronic disease, and accordingly, overweight and obese postmenopausal women are at increased risk of developing several cardiometabolic conditions (3–7). Treatments for overweight and obesity, which result in significant weight loss, frequently yield immediate improvement in the cardiometabolic risk profile (8). For most, however, long-term weight loss maintenance remains elusive (9). Data show that about one third of individuals who lose weight will regain all of their lost weight within 1 year, and almost all individuals regress to their baseline weight within 5 years (10,11). Although nearly 60% of overweight women report trying to lose weight ([12] and previous data suggest that most will be unable to maintain their weight loss), the effect of a cycle of intentional weight loss followed by weight regain on cardiometabolic risk in overweight and obese postmenopausal women is not known. Such data are necessary to assess the long-term benefits and risks of intentional weight loss in this population. Observational studies in younger adults show that weight cycling is not associated with increased cardiometabolic risk (13–15). Further, weight regain in this population is not associated with adverse effects on body composition or fat distribution (16,17). However, recent data from our group suggest that, for postmenopausal women, body composition is negatively impacted by weight regain following intentional weight loss (18). Specifically, after a 13% weight reduction, women who regained at least 2kg of lost weight within a year experienced a greater accretion of fat mass, relative to lean mass. Due to the known association between elevated body fat and cardiovascular disease risk, preferential regain of fat suggests that cardiometabolic risk factors may be worse in older adults who regain weight after intentional weight loss, although further investigation is warranted. Therefore, the purpose of this study was to determine how cardiometabolic risk factors change in the year following significant intentional weight loss in postmenopausal women and if observed, changes are affected by weight and fat regain. We also assessed whether these risk factors were worse 1 year after intentional weight loss compared with baseline values in women who experienced weight regain.

Sir—Ageing is associated with declines in physical function that lead to physical disability and loss of independence [1, 2]. Traditionally, loss of muscle mass has been thought of as the most important factor leading to loss of physical function and onset of disability. However, the number of older persons with excess fat mass is increasing [3], and a growing body of evidence shows obesity is an independent risk factor for ageing-related disability. Cross-sectional data show a higher prevalence of frailty, low function and disability, with higher body mass index (BMI) and fat mass, even in older persons with a normal amount of lean mass [4–7]. Longitudinal data also support a greater decline in physical function in more obese older adults [7, 8]. Since most mechanistic studies focus primarily on skeletal muscle, little is known regarding the mechanisms by which excess adipose tissue contributes to loss of physical ability in older adults. The relationship between excess fat and loss of function in older adults is, in part, mediated by biomechanical factors [9, 10]. However, increasing knowledge about the role of adipose tissue as an endocrine organ suggests there may also be biochemical effects of adipose tissue itself on properties of skeletal muscle that lead to loss of function, i.e. the association of excess adipose tissue with physical function decline may also be due to the secretion of inflammatory proteins by adipose tissue [11]. This premise is supported by evidence that muscle strength is lower in obese persons and in conditions characterised by chronic inflammation such as diabetes and metabolic syndrome [4, 12]. Our overall hypothesis is that adipose tissue contributes to ageing-related loss of physical function, in part, via its capacity to produce and secrete inflammatory mediators that subsequently affect skeletal muscle function. This study begins to test this hypothesis by determining whether adipose tissue gene expression of specific inflammatory adipokines, interleukin-6 (IL-6) and tumour necrosis factor-α (TNFα), is associated with clinical measures of muscle strength in overweight or obese, postmenopausal women.

Background and aims: There are no data showing whether or not age-related declines in physical function are related to in vitro properties of human skeletal muscle. The purpose of this study was to determine whether physical function is independently associated with histologic and metabolic properties of skeletal muscle in elderly adults. Methods: The study was a cross-sectional observational study of 39 sedentary, older (60–85 yrs) men and women. A needle biopsy of the vastus lateralis for assessment of muscle fiber type, fiber area, capillary density and citrate synthase and aldolase activities was performed. Physical function tests included the Short Physical Performance Battery (balance, walking speed, and chair rise time), as well as self-reported disability. Results: Total fiber area (R=−0.41, p=0.02), number of Type II fibers (R=− 0.33, p=0.05), and aldolase activity (R=−0.54, p=0.01) were inversely related to age. Persons who reported greater difficulty with daily activities had lower capillary density (R=−0.51, p=0.03) and lower citrate synthase activity (R=−0.66, p=0.03). Walking speed was directly related to fiber area (R=0.40, p=0.02), capillary density (R=0.39, p=0.03), citrate synthase (R=0.45, p=0.03) and aldolase (R=0.55, p

The aim of this study was to examine skeletal muscle mitochondria content, oxidative capacity, and the expression of key mitochondrial dynamics proteins in patients with heart failure with preserved ejection fraction (HFpEF), as well as to determine potential relationships with measures of exercise performance.Multiple lines of evidence indicate that severely reduced peak exercise oxygen uptake (peak VO2) in older patients with HFpEF is related to abnormal skeletal muscle oxygen utilization. Mitochondria are key regulators of skeletal muscle metabolism; however, little is known about how these organelles are affected in HFpEF.Both vastus lateralis skeletal muscle citrate synthase activity and the expression of porin and regulators of mitochondrial fusion were examined in older patients with HFpEF (n = 20) and healthy, age-matched control subjects (n = 17).Compared with age-matched healthy control subjects, mitochondrial content assessed by porin expression was 46% lower (p = 0.01), citrate synthase activity was 29% lower (p = 0.01), and Mfn2 (mitofusin 2) expression was 54% lower (p 0.001) in patients with HFpEF. Expression of porin was significantly positively correlated with both peak VO2 and 6-min walk distance (r = 0.48, p = 0.003 and r = 0.33, p = 0.05, respectively). Expression of Mfn2 was also significantly positively correlated with both peak VO2 and 6-min walk distance (r = 0.40, p = 0.02 and r = 0.37, p = 0.03 respectively).These findings suggest that skeletal muscle oxidative capacity, mitochondrial content, and mitochondrial fusion are abnormal in older patients with HFpEF and might contribute to their severe exercise intolerance.

Objective: Weight regain following intentional weight loss may negatively impact body composition, accelerating fat regain and increasing risk of physical disability. The purpose of this study was to compare long-term changes in whole body and thigh composition in obese older adults who intentionally lost and then partially regained weight to obese older adults who remained weight stable. Subjects/Methods: This pilot study analyzed total body (dual-energy X-ray absorptiometry (DXA)) and thigh (computed tomography (CT)) composition data collected from 24 older (65–79 years) adults 18 months after completion of a 5-month randomized trial that compared resistance training alone (RT) with RT plus caloric restriction (RT+CR). Results: Mean loss of body mass in the RT+CR group (n=13) was 7.1±2.4 kg during the 5-month intervention (74% fat mass; 26% lean mass; all P<0.01), whereas RT (n=11) remained weight stable (+0.3±1.8 kg; P=0.64). Differential group effects were observed for all DXA and CT body composition measures at 5 months (all P⩽0.01); however, by 23 months, group differences persisted only for total body (RT+CR: 81.6±10.0 kg vs RT: 88.5±14.9 kg; P=0.03) and lean (RT+CR: 50.8±9.3 kg vs RT: 54.4±12.0 kg; P<0.01) mass. All RT+CR participants regained weight from 5 to 23 months (mean gain=+4.8±2.6 kg; P<0.01). Total fat mass and all thigh fat volumes increased, whereas thigh muscle volume decreased, during the postintervention follow-up in RT+CR (all P⩽0.01). In the RT group, body mass did not change from 5 to 23 months (−0.2±0.9 kg; P=0.87). Decreased total thigh volume, driven by the loss of thigh muscle volume, were the only postintervention body composition changes observed in the RT group (both P<0.04). Conclusions: Short-term body composition benefits of an RT+CR intervention may be lost within 18 months after completion of the intervention.

Background Evidence implicates the amount and location of fat in aging-related loss of muscle function; however, whether intramyocellular lipids affect muscle contractile capacity is unknown. Methods We compared both in vivo knee extensor muscle strength, power, and quality and in vitro mechanical properties of vastus lateralis single-muscle fibers between normal weight (NW) and obese older adults and determined the relationship between muscle lipid content (both intramuscular adipose tissue and intramyocellular lipids) and in vivo and in vitro muscle function in NW and obese individuals. Results The obese group had a greater percentage of type-I fibers compared to the NW group. The cross-sectional area of type-I fibers was greater in obese compared to NW; however, maximal shortening velocity of type-I fibers in the obese was slower compared to NW. Type-I and type-IIa fibers from obese group produced lower specific force than that of type-I and type-IIa fibers from the NW group. Normalized power was also substantially lower (~50%) in type-I fibers from obese adults. The intramyocellular lipids data showed that total lipid droplet area, number of lipid droplets, and area fraction were about twofold greater in type-I fibers from the obese compared to the NW group. Interestingly, a significant inverse relationship between average number of lipid droplets and single-fiber unloaded shortening velocity, maximal velocity, and specific power was observed in obese participants. Additionally, muscle echointensity correlated with single-fiber specific force. Conclusions These data indicate that greater intramyocellular lipids are associated with slower myofiber contraction, force, and power development in obese older adults.

To describe the interindividual variability in physical function responses to supervised resistance and aerobic exercise training interventions in older adults.Data analysis of two randomized, controlled exercise trials.Community-based research centers.Overweight and obese (body mass index (BMI)≥27.0 kg/m2) sedentary men and women aged 65 to 79 (N=95).Five months of 4 d/wk of aerobic training (AT, n=40) or 3 d/wk of resistance training (RT, n=55).Physical function assessments: global measure of lower extremity function (Short Physical Performance Battery (SPPB)), 400-m walk, peak aerobic capacity (VO2 peak), and knee extensor strength.On average, both exercise interventions significantly improved physical function. For AT, there was a 7.9% increase in VO2 peak; individual absolute increases varied from 0.4 to 4.3 mL/kg per minute, and four participants (13%) showed no change or a decrease in VO2 peak. For RT, knee extensor strength improved an average of 8.1%; individual increases varied from 1.2 to 63.7 Nm, and 16 participants (30%) showed no change or a decrease in strength. Usual gait speed, 400-m walk time, chair rise time, and SPPB improved for the majority of AT participants and usual gait speed, chair rise time, and SPPB improved for the majority of RT participants, but there was wide variation in the magnitude of improvement. Only change in 400-m walk time with RT was related to exercise adherence (correlation coefficient=-0.31, P=.004).Despite sufficient levels of adherence to both exercise interventions, some participants did not improve function, and the magnitude of improvement varied widely. Additional research is needed to identify factors that optimize responsiveness to exercise to maximize its functional benefits in older adults.

Objectives: To determine whether angiotensin-converting enzyme (ACE) inhibitor use may be associated with weight maintenance and sustained muscle strength (measured by grip strength) in older adults. Design: Data from the Cardiovascular Health Study (CHS), a community-based prospective cohort study of 5,888 older adults, were used. Setting: Subjects were recruited from four U.S. sites beginning in 1989; this analysis included data through 2001. Participants: CHS participants with congestive heart failure (CHF) or treated hypertension. Measurements: The exposure, current ACE inhibitor use, was ascertained by medication inventory at annual clinic visits; the outcomes were weight change and grip-strength change during the following year. Multivariate linear regression was used, accounting for correlations between observations on the same participant over time. Results: The average annual weight change was −0.38 kg in 2,834 participants (14,443 person-years) with treated hypertension and −0.62 kg in 342 participants (980 person-years) with CHF. ACE inhibitor use was associated with less annual weight loss after adjustment for potential confounders: a difference of 0.17 kg (95% confidence interval (CI)=0.05–0.29) in those with treated hypertension and 0.29 kg (95% CI=−0.25–0.83) in those with CHF. There was no evidence of association between ACE inhibitor use and grip-strength change. Conclusion: ACE inhibitor use may be associated with weight maintenance, but not maintenance of muscle strength, in older adults with treated hypertension.

Objectives: To estimate the rate of hospitalization for pneumonia in community-dwelling older adults and to assess its risk factors and contribution to mortality. Design: Prospective observational study. Setting: The Cardiovascular Health Study (CHS) in four U.S. communities. Participants: Five thousand eight hundred eighty-eight men and women aged 65 and older who were followed for a median 10.7 years. Measurements: Participants were interviewed about medical history and demographics; evaluated for lung, physical, and cognitive function; and followed for hospitalizations, cardiovascular disease, and death. Results: Nearly 10% of the cohort was hospitalized for pneumonia, for a rate of 11.1 per 1,000 person-years (95% confidence interval (CI)=10.2–12.0). Risk factors included older age, male sex, current and past smoking, poor physical and lung function, and history of cardiovascular disease and chronic obstructive pulmonary disease. Ten percent of participants died during their incident pneumonia hospitalization, and death rates were high in those who survived to discharge. Compared with participants who had not been hospitalized for pneumonia, the relative risk of total mortality was 4.9 (95% CI=4.1–6.0) during the first year after hospitalization and 2.6 (95% CI=2.2–3.1) thereafter, adjusted for age, sex, and race. The respective relative risks were 3.9 (95% CI=3.1–4.8) and 2.0 (95% CI=1.6–2.4) after further adjustment for baseline history of cardiovascular disease; diabetes mellitus; smoking; and measures of lung, physical, and cognitive function. Conclusion: In older people, hospitalization for pneumonia is common and is associated with an elevated risk of death, as shown in this population-based, prospective cohort.

A 73-year-old woman developed an acute thrombosis of a persistent median artery following a Sisyphean struggle with a poorly fitted bedsheet. Ultrasound was able to diagnose the problem in a case where precise localization by electrodiagnostic testing was difficult.

Importance The risk of cardiovascular disease (CVD) after infection is poorly understood. Objective To determine whether hospitalization for pneumonia is associated with an increased short-term and long-term risk of CVD. Design, Settings, and Participants We examined 2 community-based cohorts: the Cardiovascular Health Study (CHS, n = 5888; enrollment age, ≥65 years; enrollment period, 1989–1994) and the Atherosclerosis Risk in Communities study (ARIC, n = 15 792; enrollment age, 45-64 years; enrollment period, 1987–1989). Participants were followed up through December 31, 2010. We matched each participant hospitalized with pneumonia to 2 controls. Pneumonia cases and controls were followed for occurrence of CVD over 10 years after matching. We estimated hazard ratios (HRs) for CVD at different time intervals, adjusting for demographics, CVD risk factors, subclinical CVD, comorbidities, and functional status. Exposures Hospitalization for pneumonia. Main Outcomes and Measures Incident CVD (myocardial infarction, stroke, and fatal coronary heart disease). Results Of 591 pneumonia cases in CHS, 206 had CVD events over 10 years after pneumonia hospitalization. CVD risk after pneumonia was highest in the first year. CVD occurred in 54 cases and 6 controls in the first 30 days (HR, 4.07; 95% CI, 2.86-5.27); 11 cases and 9 controls between 31 and 90 days (HR, 2.94; 95% CI, 2.18-3.70); and 22 cases and 55 controls between 91 days and 1 year (HR, 2.10; 95% CI, 1.59-2.60). Additional CVD risk remained elevated into the tenth year, when 4 cases and 12 controls developed CVD (HR, 1.86; 95% CI, 1.18-2.55). In ARIC, of 680 pneumonia cases, 112 had CVD over 10 years after hospitalization. CVD occurred in 4 cases and 3 controls in the first 30 days (HR, 2.38; 95% CI, 1.12-3.63); 4 cases and 0 controls between 31 and 90 days (HR, 2.40; 95% CI, 1.23-3.47); 11 cases and 8 controls between 91 days and 1 year (HR, 2.19; 95% CI, 1.20-3.19); and 8 cases and 7 controls during the second year (HR, 1.88; 95% CI, 1.10-2.66). After the second year, the HRs were no longer statistically significant. Conclusions and Relevance Hospitalization for pneumonia was associated with increased short-term and long-term risk of CVD, suggesting that pneumonia may be a risk factor for CVD.

Background: Arterial stiffness has been associated with aging, hypertension, and diabetes; however, little data has been published examining risk factors associated with arterial stiffness in elderly individuals. Methods: Longitudinal associations were made between aortic stiffness and risk factors measured approximately 4 years earlier. Aortic pulse wave velocity (PWV), an established index of arterial stiffness, was measured in 356 participants (53.4% women, 25.3% African American), aged 70 to 96 years, from the Pittsburgh site of the Cardiovascular Health Study during 1996 to 1998. Results: Mean aortic pulse wave velocity (850 cm/sec, range 365 to 1863) did not differ by ethnicity or sex. Increased aortic stiffness was positively associated with higher systolic blood pressure (SBP), age, fasting and 2-h postload glucose, fasting and 2-h insulin, triglycerides, waist circumference, body mass index, truncal fat, decreased physical activity, heart rate, and common carotid artery wall thickness (P < .05). After controlling for age and SBP, the strongest predictors of aortic stiffness in men were heart rate (P = .001) and 2-h glucose (P = .063). In women, PWV was positively associated with heart rate (P = .018), use of antihypertensive medication (P = .035), waist circumference (P = .030), and triglycerides (P = .081), and was negatively associated with physical activity (P = .111). Results were similar when the analysis was repeated in nondiabetic individuals and in those free of clinical or subclinical cardiovascular disease in 1992 to 1993. Conclusions: In these elderly participants, aortic stiffness was positively associated with risk factors associated with the insulin resistance syndrome, increased common carotid intima–media thickness, heart rate, and decreased physical activity measured several years earlier.

Pneumonia is associated with high risk of heart failure (HF) in the short term (30 days) postinfection. Whether this association persists beyond this period is unknown.We studied 5,613 elderly (≥65 years) adults enrolled in the Cardiovascular Health Study between 1989 and 1994 at 4 US communities. Participants had no clinical diagnosis of HF at enrollment, and they were followed up through December 2010. Hospitalizations for pneumonia were identified using validated International Classification of Disease Ninth Revision codes. A centralized committee adjudicated new-onset HF events. Using Cox regression, we estimated adjusted hazard ratios (HRs) of new-onset HF at different time intervals after hospitalization for pneumonia.A total of 652 participants hospitalized for pneumonia during follow-up were still alive and free of clinical diagnosis of HF by day 30 posthospitalization. Relative to the time of their hospitalization, new-onset HF occurred in 22 cases between 31 and 90 days (HR 6.9, 95% CI 4.46-10.63, P.001), 14 cases between 91 days and 6 months (HR 3.2, 95% CI 1.88-5.50, P.001), 20 cases between 6 months and 1 year (HR 2.6, 95% CI 1.64-4.04, P.001), 76 cases between 1 and 5 years (HR 1.7, 95% CI 1.30-2.12, P.001), and 71 cases after 5 years (HR 2.0, 95% CI 1.56-2.58, P.001). Results were robust to sensitivity analyses using stringent definitions of pneumonia and extreme assumptions for potential informative censoring.Hospitalization for pneumonia is associated with increased risk of new-onset HF in the intermediate and long term. Studies should characterize the mechanisms of this association in order to prevent HF in elderly pneumonia survivors.

Objectives The purpose of this study was to identify the barriers to seeking mental health treatment experienced by rural older adults. We also examined if barriers differed by age and worry severity. Methods Participants were 478 rural older adults responding to a flyer for a psychotherapy intervention study. Interested participants were screened by telephone, and barriers to mental health treatment were assessed. Participants completed a demographic questionnaire and the Penn State Worry Questionnaire-Abbreviated. Results The most commonly reported barrier to treatment was the personal belief that "I should not need help." Other commonly reported barriers included practical barriers (cost, not knowing where to go, distance), mistrust of mental health providers, not thinking treatment would help, stigma, and not wanting to talk with a stranger about private matters. Multivariable analyses indicated that worry severity and younger age were associated with reporting more barriers. Conclusions Multiple barriers interfere with older adults seeking treatment for anxiety and depression. Older age is associated with fewer barriers, suggesting that the oldest old may have found strategies for overcoming these barriers. Young-old adults may benefit from interventions addressing personal beliefs about mental health and alternative methods of service delivery.

SummaryObjectiveTo describe associations between total and regional body fat mass loss and reduction of systemic levels of inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) in obese, older adults with osteoarthritis (OA), undergoing intentional weight loss.DesignData come from a single-blind, 18-month, randomized controlled trial in adults (age: 65.6 ± 6.2; Body mass index (BMI): 33.6 ± 3.7) with knee OA. Participants were randomized to diet-induced weight loss plus exercise (D + E; n = 150), diet-induced weight loss-only (D; n = 149), or exercise-only (E; n = 151). Total body and region-specific (abdomen and thigh) fat mass were measured at baseline and 18 months. High-sensitivity CRP and IL-6 were measured at baseline, six and 18 months. Intervention effects were assessed using mixed models and associations between inflammation and adiposity were compared using logistic and mixed linear regression models.ResultsIntentional total body fat mass reduction was associated with significant reductions in log-adjusted CRP (β = 0.06 (95% CI = 0.04, 0.08) mg/L) and IL-6 (β = 0.02 (95% CI = 0.01, 0.04) pg/mL). Loss of abdominal fat volume was also associated with reduced inflammation, independent of total body fat mass; although models containing measures of total adiposity yielded the best fit. The odds of achieving clinically desirable levels of CRP (

Heart failure (HF) with preserved ejection fraction (HFPEF) is the most common form of HF in older persons. The primary chronic symptom in HFPEF is severe exercise intolerance, and its pathophysiology is poorly understood. To determine whether skeletal muscle abnormalities contribute to their severely reduced peak exercise O2 consumption (V̇o2), we examined 22 older HFPEF patients (70 ± 7 yr) compared with 43 age-matched healthy control (HC) subjects using needle biopsy of the vastus lateralis muscle and cardiopulmonary exercise testing to assess muscle fiber type distribution and capillarity and peak V̇o2. In HFPEF versus HC patients, peak V̇o2 (14.7 ± 2.1 vs. 22.9 ± 6.6 ml·kg−1·min−1, P < 0.001) and 6-min walk distance (454 ± 72 vs. 573 ± 71 m, P < 0.001) were reduced. In HFPEF versus HC patients, the percentage of type I fibers (39.0 ± 11.4% vs. 53.7 ± 12.4%, P < 0.001), type I-to-type II fiber ratio (0.72 ± 0.39 vs. 1.36 ± 0.85, P = 0.001), and capillary-to-fiber ratio (1.35 ± 0.32 vs. 2.53 ± 1.37, P = 0.006) were reduced, whereas the percentage of type II fibers was greater (61 ± 11.4% vs. 46.3 ± 12.4%, P < 0.001). In univariate analyses, the percentage of type I fibers ( r = 0.39, P = 0.003), type I-to-type II fiber ratio ( r = 0.33, P = 0.02), and capillary-to-fiber ratio ( r = 0.59, P < 0.0001) were positively related to peak V̇o2. In multivariate analyses, type I fibers and the capillary-to-fiber ratio remained significantly related to peak V̇o2. We conclude that older HFPEF patients have significant abnormalities in skeletal muscle, characterized by a shift in muscle fiber type distribution with reduced type I oxidative muscle fibers and a reduced capillary-to-fiber ratio, and these may contribute to their severe exercise intolerance. This suggests potential new therapeutic targets in this difficult to treat disorder.

Although congestive heart failure (CHF) is a common syndrome among the elderly, there is a relative paucity of population-based data, particularly regarding CHF with normal systolic left ventricular function. A total of 4,842 independent living, community-dwelling subjects aged 66 to 103 years received questionnaires on medical history, family history, personal habits, physical activity, and socioeconomic status, confirmation of pre-existing cardiovascular and cerebrovascular disease, anthropometric measurements, casual seated random-zero blood pressure, forced vital capacity and expiratory volume in 1 second, 12-lead supine electrocardiogram, fasting glucose, creatinine, plasma lipids, carotid artery wall thickness by ultrasonography, and echocardiography-Doppler examinations. Participants with at least 1 confirmed episode of CHF by Cardiovascular Health Study criteria were considered prevalent for CHF. The prevalence of CHF was 8.8% and was associated with increased age, particularly for women, in whom it increased more than twofold from age 65 to 69 years (6.6%) to age > or = 85 years (14%). In multivariate analysis, subjects with CHF were more likely to be older (odds ratio [OR] 1.2 for 5-year difference, men OR 1.1), and more often had a history of myocardial infarction (OR 7.3), atrial fibrillation (OR 3.0), diabetes mellitus (OR 2.1), renal dysfunction (OR 2.0 for creatinine < or = 1.5 mg/ dl), and chronic pulmonary disease (OR 1.8; women only). The echocardiographic correlates of CHF were increased left atrial and ventricular dimensions. Importantly, 55% of subjects with CHF had normal left ventricular systolic function and 80% had either normal or only mildly reduced systolic function. Among subjects with CHF, women had normal systolic function more frequently than men (67% vs 42%; p < 0.001). Thus, CHF is common among community-dwelling elderly. It increases with age and is usually associated with normal systolic LV function, particularly among women. The finding that a large proportion of elderly with CHF have preserved LV systolic function is important because there is a paucity of data to guide management in this dominant subset.