Trajectories in muscular strength and physical function among men with and without prostate cancer in the health aging and body composition study.
ABSTRACT: OBJECTIVES:To examine and compare changes in strength and physical function from pre- to post-diagnosis among men with prostate cancer (PC, [cases]) and matched non-cancer controls identified from the Health, Aging and Body Composition (Health ABC) study. MATERIALS AND METHODS:We conducted a longitudinal analysis of 2 strength and 3 physical function-based measures among both cases and controls, identified from a large cohort of community living older adults enrolled in the Health ABC study. We plotted trajectories for each measure and compared cases vs. controls from the point of diagnosis onwards using mixed-effects regression models. For cases only, we examined predictors of poor strength or physical function. RESULTS:We identified 117 PC cases and 453 matched non-cancer controls (50% African Americans). At baseline, there were no differences between cases and controls in demographic factors, comorbidities or self-reported physical function; however, cases had slightly better grip strength (44.6 kg vs. 41.0 kg, p<0.01), quadriceps strength (360.5 Nm vs. 338.7 Nm, p = 0.02) and Health ABC physical performance battery scores (2.4 vs. 2.3, p = 0.01). All men experienced similar declines in strength and physical function over an equivalent amount of time. The loss of quad strength was most notable, with losses of nearly two-thirds of baseline strength over approximately 7 years of follow up. CONCLUSIONS:Among both cases and controls, strength and physical function decline with increasing age. The largest declines were seen in lower body strength. Regular assessments should guide lifestyle interventions that can offset age- and treatment-related declines among men with PC.
Project description:Poor peripheral nerve function is common in older adults and may be a risk factor for strength decline, although this has not been assessed longitudinally.We assessed whether sensorimotor peripheral nerve function predicts strength longitudinally in 1,830 participants (age = 76.3 ± 2.8, body mass index = 27.2 ± 4.6kg/m(2), strength = 96.3 ± 34.7 Nm, 51.0% female, 34.8% black) from the Health ABC study. Isokinetic quadriceps strength was measured semiannually over 6 years. Peroneal motor nerve conduction amplitude and velocity were recorded. Sensory nerve function was assessed with 10-g and 1.4-g monofilaments and average vibration detection threshold at the toe. Lower-extremity neuropathy symptoms were self-reported.Worse vibration detection threshold predicted 2.4% lower strength in men and worse motor amplitude and two symptoms predicted 2.5% and 8.1% lower strength, respectively, in women. Initial 10-g monofilament insensitivity predicted 14.2% lower strength and faster strength decline in women and 6.6% lower strength in men (all p < .05).Poor nerve function predicted lower strength and faster strength decline. Future work should examine interventions aimed at preventing declines in strength in older adults with impaired nerve function.
Project description:BACKGROUND:Prostate cancer (PC) is the most frequently diagnosed non-skin malignancy in men in the Western world, yet few disease-associated mutations have been found. Recently, a low frequency recurring mutation in the HOXB13 gene was reported among both hereditary PC families and men from the general population. MATERIALS AND METHODS:We determined the distribution and frequency of the G84E HOXB13 variant in 1,310 incipient PC cases and 1,259 age-mated controls from a population-based, case-control study of PC. RESULTS:The G84E mutation was more frequent in cases than controls (1.3% vs. 0.4%, respectively), and men with the HOXB13 G84E variant had a 3.3-fold higher relative risk of PC compared with noncarriers (95% CI, 1.21-8.96). There was a stronger association between the G84E variant and PC among men with no first-degree relative with PC (OR, 4.04; 95% CI, 1.12-14.51) compared to men with a family history of PC (OR, 1.49; 95% CI, 0.30-7.50; P?=?0.36 for interaction). We observed some evidence of higher risk estimates associated with the variant for men with higher versus lower Gleason score (OR, 4.13; 95% CI, 1.38-12.38 vs. OR, 2.71; 95% CI, 0.88-8.30), and advanced versus local stage (OR, 4.47; 95% CI, 1.28-15.57 vs. OR, 2.98; 95% CI, 1.04-8.49), however these differences were not statistically different. CONCLUSIONS:These results confirm the association of a rare HOXB13 mutation with PC in the general population and suggest that this variant may be associated with features of more aggressive disease.
Project description:Age is the foremost risk factor for atrial fibrillation (AF), and AF has a rising prevalence in older adults. How AF may contribute to decline in physical performance in older adults has had limited investigation. We examined the associations of incident AF and 4-year interval declines in physical performance at ages 70, 74, 78, and 82 years in the Health, Aging, and Body Composition (Health ABC) Study.Health ABC is a prospective cohort of community-dwelling older adults (n=3075). The study conducted serial assessments of physical performance with the Health ABC physical performance battery (scored 0-4), grip strength, 2-minute walk distance, and 400-m walking time. Incident AF was identified from the Center for Medicare and Medicaid Services and related to 4-year interval decline in physical performance. After exclusions, the analysis included 2753 Health ABC participants (52% women, 41% black race). Participants with AF had a significantly greater 4-year physical performance battery decline than those without AF at age 70, 74, 78, and 82, with mean estimated decline ranging from -0.08 to -0.10 U (95% confidence interval, -0.18 to -0.01; P<0.05 for all estimates) after multivariable adjustment. Grip strength, walk distance, and walk time similarly showed significantly greater declines at each 4-year age interval in participants with AF.In community-based cohort older adults, incident AF was associated with increased risk of decline in physical performance. Further research is essential to identify mechanisms and preventive strategies for how AF may contribute toward declining physical performance in older adults.
Project description:<h4>Background</h4>Glucocorticoids used to treat childhood leukemia and lymphoma can result in osteonecrosis, leading to physical dysfunction and pain. Improving survival rates warrants research into long-term outcomes among this population.<h4>Objective</h4>The objective of this study was to compare the physical function and quality of life (QOL) of survivors of childhood cancer who had an osteonecrosis history with that of survivors who had no osteonecrosis history and with that of people who were healthy (controls).<h4>Design</h4>This was a cross-sectional study.<h4>Methods</h4>This study included St Jude Lifetime Cohort Study participants who were ? 10 years from the diagnosis of childhood leukemia or lymphoma and ? 18 years old; 135 had osteonecrosis (52.5% men; mean age = 27.7 [SD = 6.08] years) and 1560 had no osteonecrosis history (52.4% men; mean age = 33.3 [SD = 8.54] years). This study also included 272 people who were from the community and who were healthy (community controls) (47.7% men; mean age = 35.1 [SD = 10.46] years). The participants completed functional assessments and questionnaires about QOL.<h4>Results</h4>Survivors with osteonecrosis scored lower than other survivors and controls for dorsiflexion strength (mean score = 16.50 [SD = 7.91] vs 24.17 [SD = 8.61] N·m/kg) and scored lower than controls for flexibility with the sit-and-reach test (20.61 [SD = 9.70] vs 23.96 [SD = 10.73] cm), function on the Physical Performance Test (mean score = 22.73 [SD = 2.05] vs 23.58 [SD = 0.88]), and mobility on the Timed "Up & Go" Test (5.66 [SD = 2.25] vs 5.12 [SD = 1.28] seconds). Survivors with hip osteonecrosis requiring surgery scored lower than survivors without osteonecrosis for dorsiflexion strength (13.75 [SD = 8.82] vs 18.48 [SD = 9.04] N·m/kg), flexibility (15.79 [SD = 8.93] vs 20.37 [SD = 10.14] cm), and endurance on the 6-minute walk test (523.50 [SD = 103.00] vs 572.10 [SD = 102.40] m).<h4>Limitations</h4>Because some eligible survivors declined to participate, possible selection bias was a limitation of this study.<h4>Conclusions</h4>Survivors of childhood leukemia and lymphoma with and without osteonecrosis demonstrated impaired physical performance and reported reduced QOL compared with controls, with those requiring surgery for osteonecrosis most at risk for impairments. It may be beneficial to provide strengthening, flexibility, and endurance interventions for patients who have pediatric cancer and osteonecrosis for long-term function.
Project description:Skeletal muscle mitochondrial oxidative capacity declines with age and negatively affects walking performance, but the mechanism for this association is not fully clear. We tested the hypothesis that impaired oxidative capacity affects muscle performance and, through this mechanism, has a negative effect on walking speed. Muscle mitochondrial oxidative capacity was measured by in vivo phosphorus magnetic resonance spectroscopy as the postexercise phosphocreatine resynthesis rate, k<sub>PC</sub><sub>r</sub> , in 326 participants (154 men), aged 24-97 years (mean 71), in the Baltimore Longitudinal Study of Aging. Muscle strength and quality were determined by knee extension isokinetic strength, and the ratio of knee extension strength to thigh muscle cross-sectional area derived from computed topography, respectively. Four walking tasks were evaluated: a usual pace over 6 m and for 150 s, and a rapid pace over 6 m and 400 m. In multivariate linear regression analyses, k<sub>PC</sub><sub>r</sub> was associated with muscle strength (? = 0.140, P = 0.007) and muscle quality (? = 0.127, P = 0.022), independent of age, sex, height, and weight; muscle strength was also a significant independent correlate of walking speed (P < 0.02 for all tasks) and in a formal mediation analysis significantly attenuated the association between k<sub>PC</sub><sub>r</sub> and three of four walking tasks (18-29% reduction in ? for k<sub>PC</sub><sub>r</sub> ). This is the first demonstration in human adults that mitochondrial function affects muscle strength and that inefficiency in muscle bioenergetics partially accounts for differences in mobility through this mechanism.
Project description:Testosterone in Older Men with Mobility Limitations Trial determined the effects of testosterone on muscle performance and physical function in older men with mobility limitation. Trial's Data and Safety Monitoring Board recommended enrollment cessation due to increased frequency of adverse events in testosterone arm. The changes in muscle performance and physical function were evaluated in relation to participant's perception of change.Men aged 65 years and older, with mobility limitation, total testosterone 100-350 ng/dL, or free testosterone less than 50 pg/mL, were randomized to placebo or 10 g testosterone gel daily for 6 months. Primary outcome was leg-press strength. Secondary outcomes included chest-press strength, stair-climb, 40-m walk, muscle mass, physical activity, self-reported function, and fatigue. Proportions of participants exceeding minimally important difference in study arms were compared.Of 209 randomized participants, 165 had follow-up efficacy measures. Mean (SD) age was 74 (5.4) years and short physical performance battery score 7.7 (1.4). Testosterone arm exhibited greater improvements in leg-press strength, chest-press strength and power, and loaded stair-climb than placebo. Compared with placebo, significantly greater proportion of men receiving testosterone improved their leg-press and chest-press strengths (43% vs 18%, p = .01) and stair-climbing power (28% vs 10%, p = .03) more than minimally important difference. Increases in leg-press strength and stair-climbing power were associated with changes in testosterone levels and muscle mass. Physical activity, walking speed, self-reported function, and fatigue did not change.Testosterone administration in older men with mobility limitation was associated with patient-important improvements in muscle strength and stair-climbing power. Improvements in muscle strength and only some physical function measures should be weighed against the risk of adverse events in this population.
Project description:<b>Aim: </b>This study aimed to identify differences in physical performance across various socioeconomic groups within an older population and to convert those differences into a common metric to facilitate comparisons of aging speed across socioeconomic subgroups.<br><br><b>Methods: </b>We employed data from the 2009 National Health Examination Survey of Thailand. Physical performance was assessed using three health characteristics: grip strength, as a measure of upper body strength; walking speed, as a measure of lower body strength; and a combined measure of grip strength and walking speed, to capture the strength of the whole body. Education level and income were used to distinguish socioeconomic subpopulations. We followed a characteristic-based age approach to transform these population characteristics, which were measured in different units, into a common and comparable aging metric, referred to as ? - age.<br><br><b>Results: </b>Physical aging trajectories varied by sex and socioeconomic status. Some education, particularly secondary or higher education levels, was significantly associated with greater physical strength in older age for both men and women, whereas higher income was significantly associated with physical strength only for men. Across the three health characteristics, having a primary education slowed age-related declines by up to 6.3 years among men and 2.8 years among women, whereas being in a higher income group slowed age-related declines by 8.2 years among men and up to 4.9 years among women.<br><br><b>Conclusions: </b>This study adds new evidence from a developing Asian country regarding the difference in aging speeds across subpopulations associated with different levels of education and income.
Project description:Cross-sectional studies have observed that muscle weakness is associated with worse physical function among women with systemic lupus erythematosus (SLE). The present study examines whether reduced upper and lower extremity muscle strength predict declines in function over time among adult women with SLE.One hundred forty-six women from a longitudinal SLE cohort participated in the study. All measures were collected during in-person research visits approximately 2 years apart. Upper extremity muscle strength was assessed by grip strength. Lower extremity muscle strength was assessed by peak knee torque of extension and flexion. Physical function was assessed using the Short Physical Performance Battery (SPPB). Regression analyses modeled associations of baseline upper and lower extremity muscle strength with followup SPPB scores controlling for baseline SPPB, age, SLE duration, SLE disease activity (Systemic Lupus Activity Questionnaire), physical activity level, prednisone use, body composition, and depression. Secondary analyses tested whether associations of baseline muscle strength with followup in SPPB scores differed between intervals of varying baseline muscle strength.Lower extremity muscle strength strongly predicted changes over 2 years in physical function even when controlling for covariates. The association of reduced lower extremity muscle strength with reduced physical function in the future was greatest among the weakest women.Reduced lower extremity muscle strength predicted clinically significant declines in physical function, especially among the weakest women. Future studies should test whether therapies that promote preservation of lower extremity muscle strength may prevent declines in function among women with SLE.
Project description:Mitochondrial function in human skeletal muscle declines with aging, possibly because of damage accumulation caused by reactive oxygen species (ROS) produced during oxidative phosphorylation. However, most evidence for such a decline comes from studies based on indirect methods and the clinical relevance of this decline with respect to physical function has not been clearly delineated. We hypothesized that mitochondrial respiration objectively assessed in permeabilized human muscle fibers declines with aging, correlates with phosphocreatine post exercise recovery rate (kPCr) assessed by 31P magnetic resonance spectroscopy (MRS) and with muscle performance and aerobic fitness. Mitochondrial respiration was assessed by high resolution respirometry in saponin-permeabilized fibers from vastus lateralis muscle biopsies of 38 participants from the Baltimore Longitudinal Study of Aging (BLSA) (21 men, age 24-91 years) who also had available measures of peak oxygen consumption (VO2max) from treadmill tests, gait speed in different tasks, 31P magnetic resonance spectroscopy and isokinetic knee extension strength. Results indicated a significant reduction in mitochondrial respiration in older age (p<0.05) that was independent of potential confounders. Mitochondrial respiratory capacity was also associated with VO2max, muscle strength, phosphocreatine post-exercise recovery rate (kPCr), and time in 400m walk (p < 0.05). A moderate negative trend toward significance (p = 0.074) was observed between mitochondrial respiration and BMI. Finally, transcriptional profiling revealed a downregulation of mitochondrial gene networks with aging (p < 0.05). Overall, our findings reinforce the notion that mitochondrial function declines with age and is implicated in the parallel decline of muscle performance and cardiorespiratory fitness. Overall design: RNA obtained from the vastus lateralis of a subset of the participants (N=24), aged 25-84 years (mean= 67 ± 15) was analyzed by Illumina HT-12v4 microarrays, with 4 young (Y, 2M/2F), 5 middle-aged (MA, 2M, 3F), and 14 old (O, 11M, 3F) BLSA participants.
Project description:Despite documented age-related declines in self-reported functional status and measured physical capacity, it is unclear whether these functional indicators follow similar trajectories over time or whether the patterns of change differ by sex.We used longitudinal data from 687 initially nondisabled adults, aged 70 or older, from the Precipitating Events Project, who were evaluated every 18 months for nearly 14 years. Self-reported disability was assessed with a 12-item disability scale. Physical capacity was measured using grip strength and a modified version of Short Physical Performance Battery. Hierarchical linear models estimated the intra-individual trajectory of each functional indicator and differences in trajectories' intercept and slope by sex.Self-reported disability, grip strength, and Short Physical Performance Battery score declined over 13.5 years following nonlinear trajectories. Women experienced faster accumulation of self-reported disability, but slower declines in measured physical capacity, compared with men. Trajectory intercepts revealed that women had significantly weaker grip strength and reported higher levels of disability compared with men, with no differences in starting Short Physical Performance Battery scores. These findings were robust to adjustments for differences in sociodemographic characteristics, length-of-survival, health risk factors, and chronic-disease status.Despite the female disadvantage in self-reported disability, older women preserve measured physical capacity better than men over time. Self-reported and measured indicators should be viewed as complementary rather than interchangeable assessments of functional status for both clinical and research purposes, especially for sex-specific comparisons.