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ImportanceSome weight loss and exercise programs that have been successful in academic center–based trials have not been evaluated in community settings.ObjectiveTo determine whether adaptation of a diet and exercise intervention to community settings resulted in a statistically significant reduction in pain, compared with an attention control group, at 18-month follow-up.Design, Setting, and ParticipantsAssessor-blinded randomized clinical trial conducted in community settings in urban and rural counties in North Carolina. Patients were men and women aged 50 years or older with knee osteoarthritis and overweight or obesity (body mass index ≥27). Enrollment (N = 823) occurred between May 2016 and August 2019, with follow-up ending in April 2021.InterventionsPatients were randomly assigned to either a diet and exercise intervention (n = 414) or an attention control (n = 409) group for 18 months.Main Outcomes and MeasuresThe primary outcome was the between-group difference in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain score (range, 0 [none] to 20 [severe]; minimum clinically important difference, 1.6) over 18 months, tested using a repeated-measures mixed linear model with adjustments for covariates. There were 7 secondary outcomes including body weight.ResultsAmong the 823 randomized patients (mean age, 64.6 years; 637 [77%] women), 658 (80%) completed the trial. At 18-month follow-up, the adjusted mean WOMAC pain score was 5.0 in the diet and exercise group (n = 329) compared with 5.5 in the attention control group (n = 316) (adjusted difference, −0.6; 95% CI, −1.0 to −0.1; P = .02). Of 7 secondary outcomes, 5 were significantly better in the intervention group compared with control. The mean change in unadjusted 18-month body weight for patients with available data was −7.7 kg (8%) in the diet and exercise group (n = 289) and −1.7 kg (2%) in the attention control group (n = 273) (mean difference, −6.0 kg; 95% CI, −7.3 kg to −4.7 kg). There were 169 serious adverse events; none were definitely related to the study. There were 729 adverse events; 32 (4%) were definitely related to the study, including 10 body injuries (9 in diet and exercise; 1 in attention control), 7 muscle strains (6 in diet and exercise; 1 in attention control), and 6 trip/fall events (all 6 in diet and exercise).Conclusions and RelevanceAmong patients with knee osteoarthritis and overweight or obesity, diet and exercise compared with an attention control led to a statistically significant but small difference in knee pain over 18 months. The magnitude of the difference in pain between groups is of uncertain clinical importance.Trial RegistrationClinicalTrials.gov Identifier: NCT02577549

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.

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.

Objective To examine the long-term effects of telephone-delivered cognitive-behavioral therapy (CBT-T) compared with nondirective supportive therapy (NST-T) in rural older adults with generalized anxiety disorder (GAD). Methods 141 adults aged 60 years and older with a principal/co-principal diagnosis of GAD were randomized to either CBT-T or NST-T. CBT-T consisted of up to 11 sessions (9 were required) focused on recognition of anxiety symptoms, relaxation, cognitive restructuring and use of coping statements, problem-solving, worry control, behavioral activation, exposure therapy, and relapse prevention, with optional chapters on sleep and pain. NST-T consisted of 10 sessions focused on providing a supportive atmosphere in which participants could share and discuss their feelings and did not provide any direct suggestions. Primary outcomes included interviewer-rated anxiety severity and self-report worry severity measured at 9 months and 15 months after randomization. Mood-specific secondary outcomes included self-report GAD symptoms and depressive symptoms. Results At 15 months, after adjustment for multiple testing, there was a significantly greater decline in general anxiety symptoms (difference in improvement: 3.31; 95% CI: 0.45–6.17; t = 2.29; df = 136; p = 0.024) and worry (difference in improvement: 3.13; 95% CI: 0.59–5.68; t = 2.43; df = 136; p = 0.016) among participants in CBT-T compared with those in the NST-T group. There were no significant differences between the conditions in terms of depressive symptoms (difference in improvement: 2.88; 95% CI: 0.17–5.60; t = 2.10; df = 136; p = 0.0376) and GAD symptoms (difference in improvement: 1.65; 95% CI: −0.20 to 3.50; t = 1.76; df = 136; p = 0.080). Conclusions CBT-T is superior to NST-T in reducing worry and anxiety symptoms 1 year after completing treatment.

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.

Objectives The purpose of this study was to compare the effects of cognitive-behavioral therapy delivered by telephone (CBT-T) and telephone-delivered nondirective supportive therapy (NST-T) on sleep, health-related quality of life, and physical disability in rural older adults with generalized anxiety disorder. Methods This was a secondary analysis of a randomized clinical trial on 141 rural-dwelling adults 60 years and older diagnosed with generalized anxiety disorder. Sleep was assessed with the Insomnia Severity Index. Health-related quality of life was assessed with the 36-item Short-Form Health Survey (SF-36). Physical disability was assessed with the Pepper Center Tool for Disability. Assessments occurred at baseline, 4 months, 9 months, and 15 months. Results Insomnia declined in both groups from baseline to 4 months, with a significantly greater improvement among participants who received CBT-T. Similarly, Mental and Physical Component Summaries of the SF-36 declined in both groups, with a differential effect favoring CBT-T. Participants in both interventions reported declines in physical disability, although there were no significant differences between the two interventions. Improvements in insomnia were maintained at the 15-month assessment, whereas between-group differences shrank on the Mental and Physical Component Summaries of the SF-36 by the 15-month assessment. Conclusion CBT-T was superior to NST-T in reducing insomnia and improving health-related quality of life. The effects of CBT-T on sleep were maintained 1 year after completing the treatment.

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.

BACKGROUND: SPRINT found that treatment of systolic hypertension to a goal of

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.

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.

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.

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.

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.

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.

Importance Generalized anxiety disorder (GAD) is common in older adults; however, access to treatment may be limited, particularly in rural areas. Objective To examine the effects of telephone-delivered cognitive behavioral therapy (CBT) compared with telephone-delivered nondirective supportive therapy (NST) in rural older adults with GAD. Design, Setting, and Participants Randomized clinical trial in the participants’ homes of 141 adults aged 60 years and older with a principal or coprincipal diagnosis of GAD who were recruited between January 27, 2011, and October 22, 2013. Interventions Telephone-delivered CBT consisted of as many as 11 sessions (9 were required) focused on recognition of anxiety symptoms, relaxation, cognitive restructuring, the use of coping statements, problem solving, worry control, behavioral activation, exposure therapy, and relapse prevention, with optional chapters on sleep and pain. Telephone-delivered NST consisted of 10 sessions focused on providing a supportive atmosphere in which participants could share and discuss their feelings and did not provide any direct suggestions for coping. Main Outcomes and Measures Primary outcomes included interviewer-rated anxiety severity (Hamilton Anxiety Rating Scale) and self-reported worry severity (Penn State Worry Questionnaire–Abbreviated) measured at baseline, 2 months’ follow-up, and 4 months’ follow-up. Mood-specific secondary outcomes included self-reported GAD symptoms (GAD Scale 7 Item) measured at baseline and 4 months’ follow-up and depressive symptoms (Beck Depression Inventory) measured at baseline, 2 months’ follow-up, and 4 months’ follow-up. Among the 141 participants, 70 were randomized to receive CBT and 71 to receive NST. Results At 4 months’ follow-up, there was a significantly greater decline in worry severity among participants in the telephone-delivered CBT group (difference in improvement, −4.07; 95% CI, −6.26 to −1.87; P = .004) but no significant differences in general anxiety symptoms (difference in improvement, −1.52; 95% CI, −4.07 to 1.03; P = .24). At 4 months’ follow-up, there was a significantly greater decline in GAD symptoms (difference in improvement, −2.36; 95% CI, −4.00 to −0.72; P = .005) and depressive symptoms (difference in improvement, −3.23; 95% CI, −5.97 to −0.50; P = .02) among participants in the telephone-delivered CBT group. Conclusions and Relevance In this trial, telephone-delivered CBT was superior to telephone-delivered NST in reducing worry, GAD symptoms, and depressive symptoms in older adults with GAD. Trial Registration clinicaltrials.gov Identifier:NCT01259596.

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.

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.

Background Generalized Anxiety Disorder (GAD), characterized by excessive and uncontrollable worry, has a negative impact on the health, well-being, and functioning of older adults. Cognitive behavioral therapy has demonstrated efficacy in reducing anxiety and worry in older adults, but the generalizability of these findings to community-dwelling older adults is unknown. The aim of the current study is to examine the efficacy of a cognitive-behavioral intervention delivered by telephone in reducing anxiety and worry in rural community-dwelling older adults with GAD. Methods/Design We propose a randomized controlled trial comparing telephone-delivered cognitive behavioral therapy (CBT-T) with nondirective supportive therapy (NST-T). One hundred seventy six adults 60 years and older diagnosed with GAD will be randomized to one of the two treatment conditions. The primary outcomes are self-report worry and clinician-rated anxiety. Secondary outcomes include depressive symptoms, sleep, quality of life, and functional status. Discussion It is hypothesized that CBT-T will be superior to NST-T in reducing anxiety and worry among older adults with GAD. Further, CBT-T is hypothesized to be superior to NST-T in reducing problems with depressive symptoms, sleep, functional status and quality of life. If this program is successful, it could be implemented as a low-cost program to treat late-life anxiety, especially in rural areas or in circumstances where older adults may not have access to qualified mental health providers. Trial registration clinicaltrials.gov Identifier: NCT01259596

Knee osteoarthritis (OA), a common cause of chronic pain and disability, has biomechanical and inflammatory origins and is exacerbated by obesity.To determine whether a ≥10% reduction in body weight induced by diet, with or without exercise, would improve mechanistic and clinical outcomes more than exercise alone.Single-blind, 18-month, randomized clinical trial at Wake Forest University between July 2006 and April 2011. The diet and exercise interventions were center-based with options for the exercise groups to transition to a home-based program. Participants were 454 overweight and obese older community-dwelling adults (age ≥55 years with body mass index of 27-41) with pain and radiographic knee OA.Intensive diet-induced weight loss plus exercise, intensive diet-induced weight loss, or exercise.Mechanistic primary outcomes: knee joint compressive force and plasma IL-6 levels; secondary clinical outcomes: self-reported pain (range, 0-20), function (range, 0-68), mobility, and health-related quality of life (range, 0-100).Three hundred ninety-nine participants (88%) completed the study. Mean weight loss for diet + exercise participants was 10.6 kg (11.4%); for the diet group, 8.9 kg (9.5%); and for the exercise group, 1.8 kg (2.0%). After 18 months, knee compressive forces were lower in diet participants (mean, 2487 N; 95% CI, 2393 to 2581) compared with exercise participants (2687 N; 95% CI, 2590 to 2784, pairwise difference [Δ](exercise vs diet )= 200 N; 95% CI, 55 to 345; P = .007). Concentrations of IL-6 were lower in diet + exercise (2.7 pg/mL; 95% CI, 2.5 to 3.0) and diet participants (2.7 pg/mL; 95% CI, 2.4 to 3.0) compared with exercise participants (3.1 pg/mL; 95% CI, 2.9 to 3.4; Δ(exercise vs diet + exercise) = 0.39 pg/mL; 95% CI, -0.03 to 0.81; P = .007; Δ(exercise vs diet )= 0.43 pg/mL; 95% CI, 0.01 to 0.85, P = .006). The diet + exercise group had less pain (3.6; 95% CI, 3.2 to 4.1) and better function (14.1; 95% CI, 12.6 to 15.6) than both the diet group (4.8; 95% CI, 4.3 to 5.2) and exercise group (4.7; 95% CI, 4.2 to 5.1, Δ(exercise vs diet + exercise) = 1.02; 95% CI, 0.33 to 1.71; P(pain) = .004; 18.4; 95% CI, 16.9 to 19.9; Δ(exercise vs diet + exercise), 4.29; 95% CI, 2.07 to 6.50; P(function ) .001). The diet + exercise group (44.7; 95% CI, 43.4 to 46.0) also had better physical health-related quality of life scores than the exercise group (41.9; 95% CI, 40.5 to 43.2; Δ(exercise vs diet + exercise) = -2.81; 95% CI, -4.76 to -0.86; P = .005).Among overweight and obese adults with knee OA, after 18 months, participants in the diet + exercise and diet groups had more weight loss and greater reductions in IL-6 levels than those in the exercise group; those in the diet group had greater reductions in knee compressive force than those in the exercise group.clinicaltrials.gov Identifier: NCT00381290.

OBJECTIVE: To define reference hematologic and biochemical lab values in older individuals. DESIGN: Randomly selected, age- and gender-stratified participants. SETTING: Visits by participants to four research clinics. PATIENTS: A total of 5201 participants in the Cardiovascular Health Study, an observational study of older Medicare-eligible individuals living at home. MEASUREMENT: Information about health status, previous illness, and medication use was obtained from participants and/or their MDs. This information was used to define a healthy subset of the population. Blood samples were obtained for Cholesterol, HDL and LDL cholesterol, fasting and 2-hour postload glucose and insulin, fibrinogen, factors VII and VIII, potassium, creatinine, albumin, uric acid, white blood count, hematocrit, hemoglobin, and platelet count. RESULTS: Significant differences were found for age group and/or gender for all mean values. Many tests were significantly different from the generally accepted reference ranges used in clinical laboratories. CONCLUSIONS: In some situations accepted laboratory norms for the general population can not be extrapolated to older adults. There are implications for both research and clinical practice. J Am Geriatr Soc 43:855–859, 1995.

Age-related increases in ectopic fat accumulation are associated with greater risk for metabolic and cardiovascular diseases, and physical disability. Reducing skeletal muscle fat and preserving lean tissue are associated with improved physical function in older adults. PPARγ-agonist treatment decreases abdominal visceral adipose tissue (VAT) and resistance training preserves lean tissue, but their effect on ectopic fat depots in nondiabetic overweight adults is unclear. We examined the influence of pioglitazone and resistance training on body composition in older (65-79 years) nondiabetic overweight/obese men (n = 48, BMI = 32.3 ± 3.8 kg/m(2)) and women (n = 40, BMI = 33.3 ± 4.9 kg/m(2)) during weight loss. All participants underwent a 16-week hypocaloric weight-loss program and were randomized to receive pioglitazone (30 mg/day) or no pioglitazone with or without resistance training, following a 2 × 2 factorial design. Regional body composition was measured at baseline and follow-up using computed tomography (CT). Lean mass was measured using dual X-ray absorptiometry. Men lost 6.6% and women lost 6.5% of initial body mass. The percent of fat loss varied across individual compartments. Men who were given pioglitazone lost more visceral abdominal fat than men who were not given pioglitazone (-1,160 vs. -647 cm(3), P = 0.007). Women who were given pioglitazone lost less thigh subcutaneous fat (-104 vs. -298 cm(3), P = 0.002). Pioglitazone did not affect any other outcomes. Resistance training diminished thigh muscle loss in men and women (resistance training vs. no resistance training men: -43 vs. -88 cm(3), P = 0.005; women: -34 vs. -59 cm(3), P = 0.04). In overweight/obese older men undergoing weight loss, pioglitazone increased visceral fat loss and resistance training reduced skeletal muscle loss. Additional studies are needed to clarify the observed gender differences and evaluate how these changes in body composition influence functional status.

Objective: To describe relationships between age and subclinical cardiovascular disease, manifest chronic disease, and physical functioning and limitations among persons aged 65 years and older, with emphasis on the “oldest old,” those 85 years and older. Design: Observational population-based study. Setting: Four U.S. communities: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. Participants: 5,201 men and women aged 65 years and older. Measurements: Demographic data; histories of cardiovascular disease (CVD), chronic lung disease, arthritis, diabetes, and hypertension; measures of subclinical disease including arm and ankle blood pressures, internal carotid wall thickness and stenosis, ejection fraction, left ventricular mass, fractional shortening, and diastolic function, electrocardiographic left ventricular hypertrophy and cardiac injury score, forced expiratory flow and volume; functional status including self-reported physical functioning, hearing and sight limitations and health status, and performance-based measures of function. These variables were examined among men and women in three age groups: 65–74 years, 75–84 years, and 85+ years. Subgroups of participants with and without manifest CVD were also examined. Main Results: In women, the prevalence of CVD and other chronic conditions increased with age, and the highest rates occurred among those 85 years and older. In men, prevalence rates increased between the two younger groups, but the oldest group had lower than expected rates for coronary heart disease, cerebrovascular disease, hypertension, and chronic lung disease. In contrast, there were strong age-related linear trends in most of the subclinical measures of blood pressure, atherosclerosis and pulmonary function and in virtually all measures of functional status in both gender groups across the age range. There was a particularly marked decline in functional status between the two older age groups. While subclinical disease was greater and functional status was poorer among those with manifest CVD, with few exceptions, age-related trends were not significantly different between the two groups. Conclusions: Lower than expected prevalence rates of CVD among those aged 85 years and older, particularly among men, in this study of community-dwelling elderly may represent selection bias or a real plateauing in disease prevalence with age. However, subclinical disease appears to increase and functional status to decline across the age range in both men and women regardless of the presence of CVD. The apparent increase in subclinical disease with age indicates potential for CVD prevention after age 65.

MORE than one third of adults aged 65 years and older fall every year (1–3); this proportion increases with age (4). Falls have serious consequences in the elderly population, including injury (2,3), fear of falling again (5), depression (5), admission to a long-term care facility (6), and death (7). Approximately, 5% of all falls result in a serious injury (2,3), leading to substantial medical costs (8). The number of injuries and medical costs associated with falling will likely increase as the U.S. population ages. Identifying risk factors for falls in the elderly has long been of interest to researchers and clinicians intent on reducing morbidity and mortality in this age group. Impaired cognition is a risk factor for recurrent falls (9,10), injurious falls (11,12), and serious falls requiring hospitalization (13,14). There is also a strong relationship between falls, cognition, and physical function. Complex measures of physical function can predict cognitive decline (15) and falls (16) in healthy older adults. Specifically, low scores on tests of speed and executive function, including the Digit Symbol Substitution Test (DSST), are associated with increased risk of a fall (17). Incident stroke is associated with a subsequent decrease in cognition (18); many older adults with mild cognitive impairment also present with gait dysfunction (19). However, it is unknown whether decreased cognition, above the threshold of impairment, is also a risk factor for serious falls. Identifying a relationship between increasing levels of impairment in global cognition or specific cognitive domains may help to identify elderly subpopulations most at risk for serious falls. The objective of this study was to determine if decreased global cognitive function, processing speed, or both, as measured by standardized cognitive tests, are associated with increased risk of serious falls resulting in hospitalization in older adults. Hospitalization and study records from the Cardiovascular Health Study (CHS), a large longitudinal study population with 15 years of follow-up, were used to examine this association.

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.Data from the Cardiovascular Health Study (CHS), a community-based prospective cohort study of 5,888 older adults, were used.Subjects were recruited from four U.S. sites beginning in 1989; this analysis included data through 2001.CHS participants with congestive heart failure (CHF) or treated hypertension.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.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.ACE inhibitor use may be associated with weight maintenance, but not maintenance of muscle strength, in older adults with treated hypertension.

To estimate the rate of hospitalization for pneumonia in community-dwelling older adults and to assess its risk factors and contribution to mortality.Prospective observational study.The Cardiovascular Health Study (CHS) in four U.S. communities.Five thousand eight hundred eighty-eight men and women aged 65 and older who were followed for a median 10.7 years.Participants were interviewed about medical history and demographics; evaluated for lung, physical, and cognitive function; and followed for hospitalizations, cardiovascular disease, and death.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.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.

SummaryObjectiveTo determine the effects of dietary-induced weight loss (D) and weight loss plus exercise (D + E) compared to exercise alone (E) on bone mineral density (BMD) in older adults with knee osteoarthritis (OA).DesignData come from 284 older (66.0 ± 6.2 years), overweight/obese (body mass index (BMI) 33.4 ± 3.7 kg/m2), adults with knee OA enrolled in the Intensive Diet and Exercise for Arthritis (IDEA) study. Participants were randomized to 18 months of walking and strength training (E; n = 95), dietary-induced weight loss targeting 10% of baseline weight (D; n = 88) or a combination of the two (D + E; n = 101). Body weight and composition (DXA), regional BMD, were obtained at baseline and 18 months.ResultsE, D, and D + E groups lost 1.3 ± 4.5 kg, 9.1 ± 8.6 kg and 10.4 ± 8.0 kg, respectively (P

Background: Muscle loss and fat gain contribute to the disability, pain, and morbidity associated with knee osteoarthritis (OA), and thigh muscle weakness is an independent and modifiable risk factor for it. However, while all published treatment guidelines recommend muscle strengthening exercise to combat loss of muscle mass and strength in knee OA patients, previous strength training studies either used intensities or loads below recommended levels for healthy adults or were generally short, lasting only 6 to 24 weeks. The efficacy of high-intensity strength training in improving OA symptoms, slowing progression, and affecting the underlying mechanisms has not been examined due to the unsubstantiated belief that it might exacerbate symptoms. We hypothesize that in addition to short-term clinical benefits, combining greater duration with high-intensity strength training will alter thigh composition sufficiently to attain long-term reductions in knee-joint forces, lower pain levels, decrease inflammatory cytokines, and slow OA progression. Methods/Design: This is an assessor-blind, randomized controlled trial. The study population consists of 372 older (age ≥ 55 yrs) ambulatory, community-dwelling persons with: (1) mild-to-moderate medial tibiofemoral OA (Kellgren-Lawrence (KL) = 2 or 3); (2) knee neutral or varus aligned knee ( -2° valgus ≤ angle ≤ 10° varus); (3) 20 kg . m -2 ≥ BMI ≤ 45 kg . m -2 ; and (3) no participation in a formal strength-training program for more than 30 minutes per week within the past 6 months. Participants are randomized to one of 3 groups: high-intensity strength training (75-90% 1Repetition Maximum (1RM)); low-intensity strength training (30-40%1RM); or healthy living education. The primary clinical aim is to compare the interventions’ effects on knee pain, and the primary mechanistic aim is to compare their effects on knee-joint compressive forces during walking, a mechanism that affects the OA disease pathway. Secondary aims will compare the interventions’ effects on additional clinical measures of disease severity (e.g., function, mobility); disease progression measured by x-ray; thigh muscle and fat volume, measured by computed tomography (CT); components of thigh muscle function, including hip abductor strength and quadriceps strength, and power; additional measures of knee-joint loading; inflammatory and OA biomarkers; and health-related quality of life. Discussion: Test-retest reliability for the thigh CT scan was: total thigh volume, intra-class correlation coefficients (ICC) = 0.99; total fat volume, ICC = 0.99, and total muscle volume, ICC = 0.99. ICC for both isokinetic concentric knee flexion and extension strength was 0.93, and for hip-abductor concentric strength was 0.99. The reliability of our 1RM testing was: leg press, ICC = 0.95; leg curl, ICC = 0.99; and leg extension, ICC = 0.98. Results of this trial will provide critically needed guidance for clinicians in a variety of health professions who prescribe and oversee treatment and prevention of OA-related complications. Given the prevalence and impact of OA and the widespread availability of this intervention, assessing the efficacy of optimal strength training has the potential for immediate and vital clinical impact. Trial registration: ClinicalTrials.gov, NCT01489462