Clinical Results of Direct Anterior Approach THA with Minimal Fluoroscopic Exposure Optimization Techniques.

PURPOSE: To determine if low-level intraoperative fluoroscopy usage is associated with increased complications during an initial series for an experienced surgeon transitioning to direct anterior approach (DAA) for total hip arthroplasty (THA). MATERIALS AND METHODS: Subjects who underwent DAA were eligible for analysis. Inclusion criteria included the first 50 subjects who underwent DA hip arthroplasty by a single surgeon (January 2013 to December 2014). Total operating room (OR) time, fluoroscopy absorbed dose, flouoroscopy time, procedure time, and complications were collected and analyzed. Subject demographics were also collected with subjects divided by date of surgery to one of two possible groups. Simple linear regression analysis was performed to determine the relation between case number and both radiation dose and fluoroscopy time. RESULTS: Subjects underwent DAA total hip arthroplasty (n=45). Total OR time ranged from 1.1hrs up to 2.5 hours. Surgeries required an average fluoroscopic time of 7.8 seconds, with improvement over the series of 3.7 seconds. The average radiation dose or fluoroscopy was 2.6 mrem per case. This resulted in a total estimated exposure of 127 mrem over a 23-month period. No patients suffered intraoperative or postoperative fractures or revisions. No significant difference was found for the groups by weight, age, height, and body mass index. Regression analysis yielded a statistically significant (p<0.05) decrease in fluoroscopy time of 0.36 seconds per case over the 45 cases studied. CONCLUSION: An experienced single surgeon's learning curve in DAA THA can be accelerated, with proper training and technique, within a lifetime case experience less than 50 procedures. Surgeons should be aware that with proper techniques and sufficiently-experienced teams, a flattened learning curve is attainable while minimizing fluoroscopy exposure and maintaining clinical outcomes.

Rest-activity patterns and falls and fractures in older men.

Dysregulated rest-activity rhythm (RAR) patterns have been associated with several health conditions in older adults. This study showed that later acrophase was associated with a modestly greater risk of falls but not fractures in elderly men. Associations between dysregulated RAR patterns and osteoporosis risk warrant further investigation. PURPOSE: The purpose of this study was to investigate the relationship between rest-activity rhythm (RAR) patterns and risk of falls/fractures in older men. We hypothesized that dysregulated RAR would be associated with incident falls/fractures. METHODS: We used wrist-worn actigraphy to measure RAR over 4.8 ± 0.8 24-h periods in men (≥67 years) enrolled in the multicenter Outcomes of Sleep Disorders in Men (MrOS Sleep) Study (n = 3001). Men were contacted every 4 months to report occurrence of falls/fractures. RAR parameters included amplitude (difference between peak and nadir activity in counts/minute), mesor (activity counts/minute), acrophase (time of day of peak activity), and pseudo-F statistic (rhythm robustness) and were evaluated as continuous variables with associations reported per SD increase/decrease in models adjusted for confounders. Logistic regression was used to estimate the likelihood (odds ratio, OR) of recurrent falls in the year after the visit. Proportional hazards models were used to estimate the risk (hazard ratio, HR) of fractures. RESULTS: One year after the visit, 417 men (14%) had recurrent (≥2) falls. Later acrophase (OR 1.18, 95% CI 1.06-1.32) was associated with a modestly greater likelihood of falls. In 8.6 years (SD 2.6 years) of >97% complete follow-up, 256 men (8.53%) had a major osteoporotic fracture, 85 (2.8%) had a clinical spine fracture, and 110 (3.7%) had a hip fracture. No consistent, significant associations were observed between RAR patterns and fractures. CONCLUSIONS: Later acrophase was associated with a modestly greater risk of falls; this association did not translate into a higher fracture risk in this cohort of elderly men.

Sleep-disordered Breathing and Incident Heart Failure in Older Men.

RATIONALE: The directionality of the relationship between sleep-disordered breathing and heart failure is controversial. OBJECTIVES: We assessed whether elevations in the obstructive or central sleep apnea index or the presence of Cheyne-Stokes breathing are associated with decompensated and/or incident heart failure. METHODS: We conducted a prospective, longitudinal study of 2,865 participants derived from the Osteoporotic Fractures in Men Study, a prospective multicenter observational study of community-dwelling older men. Participants underwent baseline polysomnography and were followed for a mean 7.3 years for development of incident or decompensated heart failure. Our main exposures were the obstructive apnea-hypopnea index (AHI), central apnea index (CAI ≥ 5), and Cheyne-Stokes breathing. Covariates included age, race, clinic site, comorbidities, physical activity, and alcohol and tobacco use. MEASUREMENTS AND MAIN RESULTS: CAI greater than or equal to five and presence of Cheyne-Stokes breathing but not obstructive AHI were significant predictors of incident heart failure (adjusted hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.16-2.77 for CAI ≥ 5) (HR, 2.23; 95% CI, 1.45-3.43 for Cheyne-Stokes breathing). After excluding those with baseline heart failure, the incident risk of heart failure was attenuated for those with CAI greater than or equal to five (HR, 1.57; 95% CI, 0.92-2.66) but remained significantly elevated for those with Cheyne-Stokes breathing (HR, 1.90; 95% CI, 1.10-3.30). CONCLUSIONS: An elevated CAI/Cheyne-Stokes breathing, but not an elevated obstructive AHI, is significantly associated with increased risk of decompensated heart failure and/or development of clinical heart failure in a community-based cohort of older men.

Central Sleep-disordered Breathing Predicts Incident Atrial Fibrillation in Older Men.

RATIONALE: Although research supports a sleep-disordered breathing and atrial fibrillation association, prospective data examining sleep-disordered breathing predicting incident atrial fibrillation are lacking. OBJECTIVES: To investigate sleep-disordered breathing indices as predictors of incident atrial fibrillation. METHODS: A cohort (n = 843) of ambulatory older men without prevalent atrial fibrillation was assessed for baseline sleep indices: apnea-hypopnea index, central sleep apnea (central apnea index, ≥5 vs. <5), central sleep apnea or Cheyne-Stokes respiration, obstructive apnea-hypopnea index, and percentage of sleep time with less than 90% oxygen saturation. Incident clinically symptomatic adjudicated or self-reported atrial fibrillation outcome was ascertained (mean follow-up, 6.5 ± 0.7 yr). We used logistic regression models adjusted for age, race, body mass index, cardiopulmonary disease, alcohol use, pacemaker, cholesterol, cardiac medications, and alternate apnea type for obstructive and central apnea. Age interaction terms and median age-stratified analyses were performed. MEASUREMENTS AND MAIN RESULTS: Central sleep apnea (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.18-5.66) and Cheyne-Stokes respiration with central sleep apnea (OR, 2.27; 95% CI, 1.13-4.56), but not obstructive apnea or hypoxemia, predicted incident atrial fibrillation. Central apnea, Cheyne-Stokes respiration, and sleep-disordered breathing-age interaction terms were significant (P < 0.05). Unlike the case with younger participants, among participants aged 76 years or older (albeit with small atrial fibrillation counts), atrial fibrillation was related to central apnea (OR, 9.97; 95% CI, 2.72-36.50), Cheyne-Stokes respiration with central apnea (OR, 6.31; 95% CI, 1.94-20.51), and apnea-hypopnea index (OR, 1.22; 95% CI, 1.08-1.39 [per 5-unit increase]). CONCLUSIONS: In older men, central apnea and Cheyne-Stokes respiration predicted increased atrial fibrillation risk, with findings being strongest in older participants in whom overall sleep-disordered breathing also increased atrial fibrillation risk.

Estimated GFR and Mortality in Older Men: Are All eGFR Formulae Equal.

BACKGROUND: Recently, the first estimated glomerular filtration rate (eGFR) formula specifically developed for community-dwelling older adults, the Berlin Initiative Study Equation 2 (BIS2), was reported. To date, however, no study has examined the performance of the BIS2 to predict death in older adults as compared to equations used clinically and in research. METHODS: We prospectively followed 2,994 community-dwelling men (age 76.4 ± 5.6) enrolled in the MrOS Sleep Study. We calculated baseline eGFR from serum creatinine and cystatin-C using the BIS2, Chronic Kidney Disease Epidemiology (CKD-EPIcr,cysc), CKD-EPIcysc and CKD-EPIcr equations. Analyses included Cox-proportional hazards regression and net reclassification improvement (NRI) for the outcomes of all-cause and cardiovascular death. RESULTS: Follow-up time was 7.3 ± 1.9 years. By BIS2, 42 and 11% had eGFR <60 and <45, respectively, compared to CKD-EPIcr (23 and 6%), CKD-EPIcysc (36 and 13%) and CKD-EPIcr,cysc (28 and 8%). BIS2 eGFR <45 was associated with twofold higher rate of all-cause mortality when compared to eGFR ≥75 after multivariate adjustment (HR 2.1, 95% CI 1.5-2.8). Results were similar for CKD-EPIcr,cysc <45 (HR 2.1, 95% CI 1.6-2.7) and CKD-EPIcysc <45 (HR 2.1, 95% CI 1.7-2.7) and weaker for CKD-EPIcr <45 (HR 1.5, 95% CI 1.2-2.0). In NRI analyses, when compared to CKD-EPIcr,cysc, both BIS2 and CKD-EPIcr equations more often misclassified participants with respect to mortality. We found similar results for cardiovascular death. CONCLUSION: The BIS2 did not outperform and the CKD-EPIcr was inferior to the cystatin C-based CKD-EPI equations to predict death in this cohort of older men. Thus, the cystatin C-based CKD-EPI equations are the formulae of choice to predict death in community-dwelling older men.

Restless Legs Syndrome and Depression: Effect Mediation by Disturbed Sleep and Periodic Limb Movements.

OBJECTIVE: To investigate an association between restless legs syndrome (RLS) and depression and to what extent sleep disturbance, periodic limb movements during sleep (PLMS), and antidepressant medication mediate this relationship. METHODS: A cross-sectional analysis was conducted of the Osteoporotic Fractures in Older Men Study data in 982 men assessed for RLS (International RLS Study Group scale [IRLSS]) and depression (Geriatric Depression Scale [GDS]), who underwent actigraphy (for sleep latency/efficiency) and polysomnography (for PLMS). Men were split into three groups: no RLS (N = 815), mild RLS (IRLSS ≤ 12, N = 85), moderate-to-severe RLS (IRLSS > 12, N = 82). Depression was defined as GDS score ≥ 6. Logistic and linear regression assessed associations of RLS and depression or number depressive symptoms, respectively. Models were adjusted for age, site, race, education, body mass index, personal habits, benzodiazepine/dopaminergic medication, physical activity, cardiovascular risk factors, and apnea-hypopnea index. RESULTS: Of 982 men, 167 (17.0%) had RLS. Depression was significantly associated with moderate-to-severe RLS after adjustment (versus no RLS: OR [95% CI] 2.85 [1.23, 6.64]). Further adjustment for potential mediators attenuated effect size modestly, most for sleep efficiency (OR: 2.85-2.55). Compared with no RLS, moderate-to-severe RLS was associated with the number of depressive symptoms after adjustment (adjusted means [95% CI]; no RLS: 1.14 [1.05, 1.24] versus IRLSS > 12: 1.69 [1.32, 2.11]). Further adjustment for potential mediators did not alter effect size. For men with PLMS index at least median, number of depressive symptoms significantly increased as RLS category became more severe. CONCLUSION: Depression is more common as RLS severity worsens. The RLS-depression relationship is modestly explained by sleep disturbance and PLMS.

Measures of Sleep-Wake Patterns and Risk of Mild Cognitive Impairment or Dementia in Older Women.

OBJECTIVE: Sleep disturbances are common in older adults. Little is known about the sleep of cognitively intact older adults and its relationship to subsequent cognitive impairment. The objective of this study was to examine the association between objective sleep-wake measures and risk of incident cognitive impairment. METHODS: In this prospective cohort study encompassing four U.S. sites, 1,245 women (mean age: 82.6 years) without dementia participated in the Study of Osteoporotic Fractures and completed actigraphy at the baseline visit and comprehensive cognitive assessment at follow-up. The association between sleep-wake patterns measured by actigraphy and risk of incident mild cognitive impairment (MCI) and dementia was examined. RESULTS: A total of 473 women (38%) developed cognitive impairment during an average (SD) follow-up of 4.9 (0.6) years; 290 (23.3%) developed MCI and 183 (14.7%) developed dementia. After controlling for multiple potential confounders, women in the lowest quartile of average sleep efficiency (<74%) had a 1.5-fold higher odds of developing MCI or dementia compared with women in the highest quartile of sleep efficiency (>86%) (odds ratio: Q1 versus Q4 1.53; 95% CI: 1.07, 2.19; Wald χ(2) [1, N = 1,223] = 5.34 for p for trend = 0.03). Longer average sleep latency, but not total sleep time, was also associated with higher odds of developing cognitive impairment. Greater variability in both sleep efficiency and total sleep time was associated with an increased odds of developing MCI or dementia. CONCLUSION: Lower average sleep efficiency, longer average sleep latency, and greater variability in sleep efficiency and total sleep time are associated with increased odds of developing cognitive impairment. Further research is needed to explore the mechanisms underlying these associations.

Circadian rest-activity rhythms predict future increases in depressive symptoms among community-dwelling older men.

OBJECTIVE: Circadian rest-activity rhythms (CARs) have been cross-sectionally associated with depressive symptoms, although no longitudinal research has examined whether CARs are a risk factor for developing depressive symptoms. METHODS: We examined associations of CARs (measured with actigraphy over a mean of 4.8 days) with depressive symptoms (measured with the Geriatric Depression Scale) among 2,892 community-dwelling older men (mean age: 76.2 ± 5.5 years) from the MrOS Sleep Study who were without cognitive impairment. Among 2,124 men with minimal (0-2) symptoms at baseline, we assessed associations between CAR parameters and increases to mild (3-5) or clinically significant (≥6) symptoms after an average of 1.2 (±0.32) years. RESULTS: Cross-sectional associations between rhythm height parameters were independent of chronic diseases, lifestyle, sleep, and self-reported physical activity covariates. For example, men in the lowest mesor quartile had twice the adjusted odds (adjusted odds ratio [AOR]: 2.04, 95% confidence interval [CI]: 1.36-3.04, p = 0.0005) of having prevalent clinically significant symptoms (compared to minimal). Longitudinally, low CAR robustness (being in the lowest quartile of the pseudo-F statistic) was independently associated with increasing odds of developing symptoms (i.e., AOR for having clinically significant depressive symptoms at follow-up = 2.58, 95% CI: 1.11-5.99, p = 0.03). CONCLUSION: CAR disturbances are indicative of depressive symptomology. Low CAR robustness may independently contribute to the risk of worsening depression symptomology.

Vigor to Frailty As a Continuum-A New Approach in the Study of Muscle, Mobility, and Aging Cohort.

BACKGROUND: Frailty can occur in older adults without disability or multimorbidity. Current methods focus on the most frail, but poorly discriminate among those "not frail." METHODS: The Study of Muscle, Mobility, and Aging (SOMMA) included 879 adults aged 70 years and older without mobility disability. We operationalized frailty domains using: peak oxygen consumption (endurance), digit symbol substitution test (speed), leg power (strength), perceived fatigability, D3 creatine dilution (sarcopenia), and accelerometry (sedentary behavior) to construct a frailty score of 0-12 summing tertiles (0-2) of each component. We used linear or logistic regression with and without adjustment for confounders to examine associations with age, reported, and performance function. RESULTS: The SOMMA frailty score distribution was broad and strongly associated with age (r = 0.33, p < .0001). Each point was associated with a 30%-50% higher odds of having reported difficulty with activities of daily living or mobility. After grouping the total score (0-3, 4-7, and 8-12) those in the highest group were 9-31 times more likely to have functional limitation, and at least 8 times more likely to have poorer function after full adjustment. Higher scores identified those less likely to report ease of walking or higher physical activity. Peak oxygen consumption, leg power, fatigability, and digit symbol score contributed most to these associations. CONCLUSIONS: The SOMMA frailty score characterizes frailty as a continuum from frail to vigorous with assessments that are amenable to change. Associations with age and function suggest utility for distinguishing a wide range of vigor and vulnerability in relatively well-functioning older adults.

The Vitamin D Metabolite Ratio Is Associated With Volumetric Bone Density in Older Men.

CONTEXT: Serum 25-hydroxyvitamin D (25(OH)D) is the current marker of vitamin D adequacy, but its relationship with bone health has been inconsistent. The ratio of 24,25-dihydroxyvitamin D3 to 25(OH)D3 (vitamin D metabolite ratio or VMR) is a marker of vitamin D that has been associated with longitudinal changes in bone mineral density (BMD) and fracture risk. OBJECTIVE: High-resolution peripheral quantitative computed tomography (HR-pQCT) provides information on bone health beyond standard dual-energy x-ray absorptiometry, in that it measures volumetric BMD (vBMD) as well bone strength. The relationship of the VMR with vBMD and bone strength remains unknown. METHODS: We evaluated the associations of the VMR and 25(OH)D3 with vBMD and bone strength in the distal radius and tibia, assessed by HR-pQCT in 545 older men participating in the Osteoporotic Fractures in Men (MrOS) Study. Primary outcomes were vBMD and estimated failure load (EFL, a marker of bone strength) at the distal radius and tibia. RESULTS: The mean age was 84 ± 4 years, 88.3% were White, and 32% had an estimated glomerular filtration rate <60 mL/min/1.73 m2. In adjusted models, each twofold higher VMR was associated with a 9% (3%, 16%) higher total vBMD and a 13% (5%, 21%) higher EFL at the distal radius. Results were similar at the distal tibia. 25(OH)D3 concentrations were not associated with any of the studied outcomes. CONCLUSION: Among older men, a higher VMR was associated with greater vBMD and bone strength while 25(OH)D3 was not. The VMR may serve as a valuable marker of skeletal health in older men.

Cardiopulmonary Exercise Testing in a Prospective Multicenter Cohort of Older Adults.

PURPOSE: Cardiorespiratory fitness (CRF) measured by peak oxygen consumption (V̇O 2peak ) declines with aging and correlates with mortality and morbidity. Cardiopulmonary exercise testing (CPET) is the criterion method to assess CRF, but its feasibility, validity, and reliability in older adults are unclear. Our objective was to design and implement a dependable, safe, and reliable CPET protocol in older adults. METHODS: V̇O 2peak was measured by CPET, performed using treadmill exercise in 875 adults ≥70 yr in the Study of Muscle, Mobility and Aging (SOMMA). The protocol included a symptom-limited peak (maximal) exercise and two submaximal walking speeds. An adjudication process was in place to review tests for validity if they met any prespecified criteria (V̇O 2peak <12.0 mL·kg -1 ·min -1 ; maximum heart rate <100 bpm; respiratory exchange ratio <1.05 and a rating of perceived exertion <15). A subset ( N = 30) performed a repeat test to assess reproducibility. RESULTS: CPET was safe and well tolerated, with 95.8% of participants able to complete the V̇O 2peak phase of the protocol. Only 56 (6.4%) participants had a risk alert and only two adverse events occurred: a fall and atrial fibrillation. Mean ± SD V̇O 2peak was 20.2 ± 4.8 mL·kg -1 ·min -1 , peak heart rate 142 ± 18 bpm, and peak respiratory exchange ratio 1.14 ± 0.09. Adjudication was indicated in 47 tests; 20 were evaluated as valid and 27 as invalid (18 data collection errors, 9 did not reach V̇O 2peak ). Reproducibility of V̇O 2peak was high (intraclass correlation coefficient = 0.97). CONCLUSIONS: CPET was feasible, effective, and safe for older adults, including many with multimorbidity or frailty. These data support a broader implementation of CPET to provide insight into the role of CRF and its underlying determinants of aging and age-related conditions.

Role of Walking Energetics and Perceived Fatigability Differs by Gait Speed: The Study of Muscle, Mobility and Aging (SOMMA).

BACKGROUND: Slower gait speed may be driven by greater energy deficits and fatigability among older adults. We examined associations of walking energetics and perceived physical fatigability with gait speed among slower and faster walkers. Additionally, we used statistical mediation to examine the role of fatigability in the associations of walking energetics and gait speed using the Study of Muscle, Mobility and Aging (SOMMA). METHODS: Perceived physical fatigability was assessed using the Pittsburgh Fatigability Scale (PFS) Physical score (range 0-50, higher = greater). A 3-phase cardiopulmonary exercise treadmill test collected peak oxygen consumption (VO2peak, mL/kg/min), energetic cost of walking (ECW, mL/kg/m), and cost-capacity ratio (VO2/VO2peak*100, %). Slower (<1.01 m/s) versus faster (≥1.01 m/s) walkers were classified using median 4-m gait speed. Linear regressions and statistical mediation analyses were conducted. RESULTS: Slower walkers had lower VO2peak, higher ECW at preferred walking speed (PWS), and greater PFS Physical score compared to faster walkers (all p < .05; N = 849). One standard deviation (1-SD) higher VO2peak was associated with 0.1 m/s faster gait speed, while 1-SD higher ECW PWS, cost-capacity ratio at PWS and slow walking speed (SWS), and PFS Physical score were associated with 0.02-0.23 m/s slower gait speed. PFS Physical score was a significant statistical mediator in the associations between VO2peak (15.2%), SWS cost-capacity ratio (15.9%), and ECW PWS (10.7%) with gait speed and was stronger among slower walkers. CONCLUSIONS: Slower walkers may be more influenced by perceptions of fatigue in addition to walking energetics. Our work highlights the importance of targeting both energetics and perceived fatigability to prevent mobility decline.

Associations Between D3Cr Muscle Mass and Magnetic Resonance Thigh Muscle Volume With Strength, Power, Physical Performance, Fitness, and Limitations in Older Adults in the SOMMA Study.

BACKGROUND: How magnetic resonance (MR) derived thigh muscle volume and deuterated creatine dilution derived muscle mass (D3Cr muscle mass) differentially relate to strength, fitness, and other functions in older adults-and whether associations vary by sex-is not known. METHODS: Men (N = 345) and women (N = 482) aged ≥70 years from the Study of Muscle, Mobility, and Aging completed leg extension strength (1-repetition max) and cardiopulmonary exercise testing to assess fitness (VO2peak). Correlations and adjusted regression models stratified by sex were used to assess the association between muscle size measures, study outcomes, and sex interactions. RESULTS: D3Cr muscle mass and MR thigh muscle volume were correlated (men: r = 0.62, women: r = 0.51, p < .001). Each standard deviation (SD) decrement in D3Cr muscle mass was associated with lower 1-repetition max strength (-14 kg men, -4 kg women, p < .001 for both; p-interaction = .003) and lower VO2peak (-79 mL/min men, -30 mL/min women, p < .001 for both, p-interaction: .016). Each SD decrement in MR thigh muscle volume was also associated with lower strength (-32 kg men, -20 kg women, p < .001 for both; p-interaction = .139) and lower VO2peak (-217 mL/min men, -111 mL/min women, p < .001 for both, p-interaction = .010). There were associations, though less consistent, between muscle size or mass with physical performance and function; associations varied by sex. CONCLUSIONS: Less muscle-measured by either D3Cr muscle mass or MR thigh muscle volume-was associated with lower strength and fitness. Varied associations by sex and assessment method suggest consideration be given to which measurement to use in future studies.

Age Is Associated With Dampened Circadian Patterns of Rest and Activity: The Study of Muscle, Mobility, and Aging (SOMMA).

BACKGROUND: The effects of aging on circadian patterns of behavior are insufficiently described. To address this, we characterized age-specific features of rest-activity rhythms (RAR) in community-dwelling older adults both overall, and in relation, to sociodemographic characteristics. METHODS: We examined cross-sectional associations between RAR and age, sex, race, education, multimorbidity burden, financial, work, martial, health, and smoking status using assessments of older adults with wrist-worn free-living actigraphy data (N = 820, age = 76.4 years, 58.2% women) participating in the Study of Muscle, Mobility, and Aging (SOMMA). RAR parameters were determined by mapping an extension to the traditional cosine curve to activity data. Functional principal component analysis determined variables accounting for variance. RESULTS: Age was associated with several metrics of dampened RAR; women had stronger and more robust RAR versus men (all p < .05). Total activity (56%) and time of activity (20%) accounted for most of the RAR variance. Compared to the latest decile of acrophase, those in the earliest decile had higher average amplitude (p < .001). Compared to the latest decile of acrophase, those in the earliest and midrange categories had more total activity (p = .02). Being in a married-like relationship and a more stable financial situation were associated with stronger rhythms; higher education was associated with less rhythm strength (all p < .05). CONCLUSIONS: Older age was associated with dampened circadian behavior; behaviors were sexually dimorphic. Some sociodemographic characteristics were associated with circadian behavior. We identified a behavioral phenotype characterized by early time of day of peak activity, high rhythmic amplitude, and more total activity.

Lower muscle mitochondrial energetics is associated with greater phenotypic frailty in older women and men: the Study of Muscle, Mobility and Aging.

BACKGROUND: Phenotypic frailty syndrome identifies older adults at greater risk for adverse health outcomes. Despite the critical role of mitochondria in maintaining cellular function, including energy production, the associations between muscle mitochondrial energetics and frailty have not been widely explored in a large, well-phenotyped, older population. METHODS: The Study of Muscle, Mobility and Aging (SOMMA) assessed muscle energetics in older adults (N = 879, mean age = 76.3 years, 59.2% women). 31Phosporous magnetic resonance spectroscopy measured maximal production of adenosine triphosphate (ATPmax) in vivo, while ex vivo high-resolution respirometry of permeabilized muscle fibers from the vastus lateralis measured maximal oxygen consumption supported by fatty acids and complex I- and II-linked carbohydrates (e.g., Max OXPHOSCI+CII). Five frailty criteria, shrinking, weakness, exhaustion, slowness, and low activity, were used to classify participants as robust (0, N = 397), intermediate (1-2, N = 410), or frail (≥ 3, N = 66). We estimated the proportional odds ratio (POR) for greater frailty, adjusted for multiple potential confounders. RESULTS: One-SD decrements of most respirometry measures (e.g., Max OXPHOSCI+CII, adjusted POR = 1.5, 95%CI [1.2,1.8], p = 0.0001) were significantly associated with greater frailty classification. The associations of ATPmax with frailty were weaker than those between Max OXPHOSCI+CII and frailty. Muscle energetics was most strongly associated with slowness and low physical activity components. CONCLUSIONS: Our data suggest that deficits in muscle mitochondrial energetics may be a biological driver of frailty in older adults. On the other hand, we did observe differential relationships between measures of muscle mitochondrial energetics and the individual components of frailty.

Muscle Mitochondrial Bioenergetic Capacities Are Associated With Multimorbidity Burden in Older Adults: The Study of Muscle, Mobility and Aging.

BACKGROUND: The geroscience hypothesis posits that aging biological processes contribute to many age-related deficits, including the accumulation of multiple chronic diseases. Though only one facet of mitochondrial function, declines in muscle mitochondrial bioenergetic capacities may contribute to this increased susceptibility to multimorbidity. METHODS: The Study of Muscle, Mobility and Aging (SOMMA) assessed ex vivo muscle mitochondrial energetics in 764 older adults (mean age = 76.4, 56.5% women, and 85.9% non-Hispanic White) by high-resolution respirometry of permeabilized muscle fibers. We estimated the proportional odds ratio (POR [95% CI]) for the likelihood of greater multimorbidity (4 levels: 0 conditions, N = 332; 1 condition, N = 299; 2 conditions, N = 98; or 3+ conditions, N = 35) from an index of 11 conditions, per SD decrement in muscle mitochondrial energetic parameters. Distribution of conditions allowed for testing the associations of maximal muscle energetics with some individual conditions. RESULTS: Lower oxidative phosphorylation supported by fatty acids and/or complex I- and II-linked carbohydrates (eg, Max OXPHOSCI+CII) was associated with a greater multimorbidity index score (POR = 1.32 [1.13, 1.54]) and separately with diabetes mellitus (OR = 1.62 [1.26, 2.09]), depressive symptoms (OR = 1.45 [1.04, 2.00]) and possibly chronic kidney disease (OR = 1.57 [0.98, 2.52]) but not significantly with other conditions (eg, cardiac arrhythmia, chronic obstructive pulmonary disease). CONCLUSIONS: Lower muscle mitochondrial bioenergetic capacities were associated with a worse composite multimorbidity index score. Our results suggest that decrements in muscle mitochondrial energetics may contribute to a greater global burden of disease and are more strongly related to some conditions than others.

Associations of accelerometry-measured and self-reported physical activity and sedentary behavior with skeletal muscle energetics: The Study of Muscle, Mobility and Aging (SOMMA).

BACKGROUND: Skeletal muscle energetics decline with age, and physical activity (PA) has been shown to offset these declines in older adults. Yet, many studies reporting these effects were based on self-reported PA or structured exercise interventions. Therefore, we examined the associations of accelerometry-measured and self-reported PA and sedentary behavior (SB) with skeletal muscle energetics and explored the extent to which PA and sedentary behavior would attenuate the associations of age with muscle energetics. METHODS: As part of the Study of Muscle, Mobility and Aging, enrolled older adults (n = 879), 810 (age = 76.4 ± 5.0 years old, mean ± SD; 58% women) had maximal muscle oxidative capacity measured ex vivo via high-resolution respirometry of permeabilized myofibers (maximal oxidative phosphorylation (maxOXPHOS)) and in vivo by 31phosphorus magnetic resonance spectroscopy (maximal adenosine triphosphate (ATPmax)). Accelerometry-measured sedentary behavior, light activity, and moderate-to-vigorous PA (MVPA) were assessed using a wrist-worn ActiGraph GT9X over 7 days. Self-reported sedentary behavior, MVPA, and all PA were assessed with the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire. Linear regression models with progressive covariate adjustments evaluated the associations of sedentary behavior and PA with muscle energetics, as well as the attenuation of the age/muscle energetics association by MVPA and sedentary behavior. As a sensitivity analysis, we also examined activPAL-measured daily step count and time spent in sedentary behavior and their associations with muscle energetics. RESULTS: Every 30 min/day more of ActiGraph-measured MVPA was associated with 0.65 pmol/(s × mg) higher maxOXPHOS and 0.012 mM/s higher ATPmax after adjusting for age, site/technician, and sex (p < 0.05). Light activity was not associated with maxOXPHOS or ATPmax. Meanwhile, every 30 min/day spent in ActiGraph-measured sedentary behavior was associated with 0.39 pmol/s × mg lower maxOXPHOS and 0.006 mM/s lower ATPmax (p < 0.05). Only associations with ATPmax held after further adjusting for socioeconomic status, body mass index, lifestyle factors, and multimorbidity. CHAMPS MVPA and all PA yielded similar associations with maxOXPHOS and ATPmax (p < 0.05), but sedentary behavior did not. Higher activPAL step count was associated with higher maxOXHPOS and ATPmax (p < 0.05), but time spent in sedentary behavior was not. Additionally, age was significantly associated with muscle energetics for men only (p < 0.05); adjusting for time spent in ActiGraph-measured MVPA attenuated the age association with ATPmax by 58% in men. CONCLUSION: More time spent in accelerometry-measured or self-reported daily PA, especially MVPA, was associated with higher skeletal muscle energetics. Interventions aimed specifically at increasing higher intensity activity might offer potential therapeutic interventions to slow age-related decline in muscle energetics. Our work also emphasizes the importance of taking PA into consideration when evaluating associations related to skeletal muscle energetics.

Multidimensional Sleep Health and Long-Term Cognitive Decline in Community-Dwelling Older Men.

Specific sleep characteristics have been associated with cognitive decline, Alzheimer's disease, and related dementias; however, studies examining the association between multidimensional sleep (a more comprehensive integration of sleep parameters) and cognitive decline are lacking. Among 2,811 older men without dementia, those with none, 1-2, and 3-5 "poor" self-reported sleep health dimensions had an adjusted 10-year change score of global cognition (3MS) of 2.9, 4.0 and 3.5 points (p-trend = 0.05), and in executive function (Trails B) completion time of 36.7, 42.7, and 46.7 seconds (p-trend < 0.01), respectively. In conclusion, a multidimensional measure of sleep health was associated with greater cognitive decline.

Predicting Slow Walking Speed From a Pooled Cohort Analysis: Sarcopenia Definitions, Agreement, and Prevalence in Australia and New Zealand.

BACKGROUND: Recent operational definitions of sarcopenia have not been replicated and compared in Australia and New Zealand (ANZ) populations. We aimed to identify sarcopenia measures that discriminate ANZ adults with slow walking speed (<0.8 m/s) and determine the agreement between the Sarcopenia Definitions and Outcomes Consortium (SDOC) and revised European Working Group for Sarcopenia in Older People (EWGSOP2) operational definitions of sarcopenia. METHODS: Eight studies comprising 8 100 ANZ community-dwelling adults (mean age ± standard deviation, 62.0 ± 14.4 years) with walking speed, grip strength (GR), and lean mass data were combined. Replicating the SDOC methodology, 15 candidate variables were included in sex-stratified classification and regression tree models and receiver operating characteristic curves on a pooled cohort with complete data to identify variables and cut points discriminating slow walking speed (<0.8 m/s). Agreement and prevalence estimates were compared using Cohen's Kappa (CK). RESULTS: Receiver operating characteristic curves identified GR as the strongest variable for discriminating slow from normal walking speed in women (GR <20.50 kg, area under curve [AUC] = 0.68) and men (GR <31.05 kg, AUC = 0.64). Near-perfect agreement was found between the derived ANZ cut points and SDOC cut points (CK 0.8-1.0). Sarcopenia prevalence ranged from 1.5% (EWGSOP2) to 37.2% (SDOC) in women and 1.0% (EWGSOP2) to 9.1% (SDOC) in men, with no agreement (CK <0.2) between EWGSOP2 and SDOC. CONCLUSIONS: Grip strength is the primary discriminating characteristic for slow walking speed in ANZ women and men, consistent with findings from the SDOC. Sarcopenia Definitions and Outcomes Consortium and EWGSOP2 definitions showed no agreement suggesting these proposed definitions measure different characteristics and identify people with sarcopenia differently.

Cardiopulmonary Exercise Testing in a Prospective Multicenter Cohort of Older Adults: The Study of Muscle, Mobility and Aging (SOMMA).

BACKGROUND: Cardiorespiratory fitness (CRF) measured by peak oxygen consumption (VO2peak) declines with aging and correlates with mortality and morbidity. Cardiopulmonary Exercise Testing (CPET) has long been the criterion method to assess CRF, but its feasibility, efficacy and reliability in older adults is unclear. The large, multicenter Study of Muscle, Mobility and Aging (SOMMA) employed CPET to evaluate the mechanisms underlying declines in mobility with aging among community-dwelling older adults. Our primary objective was to design and implement a CPET protocol in older adults that was dependable, safe, scientifically valuable, and methodologically reliable. METHODS: CPET was performed using treadmill exercise in 875 adults ≥70 years. A composite protocol included a symptom-limited peak exercise phase and two submaximal phases to assess cardiopulmonary ventilatory indices during 1) participants' preferred walking speed and 2) at slow walking speed of 1.5 mph (0.67 m/s). An adjudication process was in place to review tests for validity if they met any prespecified criteria (VO2peak <12.0 ml/kg/min; maximum heart rate (HR) <100 bpm; respiratory exchange ratio (RER) <1.05 and a rating of perceived exertion <15). A repeat test was performed in a subset (N=30) to assess reproducibility. RESULTS: CPET was safe and well tolerated, with 95.8% of participants able to complete the VO2peak phase of the protocol. Only 56 (6.4%) participants had a risk alert during any phase of testing and only two adverse events occurred during the peak phase: a fall and atrial fibrillation. The average ± standard deviation for VO2peak was 20.2 ± 4.8 mL/kg/min, peak HR 142 ± 18 bpm, and peak RER 1.14 ± 0.09. VO2peak and RER were slightly higher in men than women. Adjudication was indicated in 47 participants; 20 were evaluated as valid, 27 as invalid (18 had a data collection error, 9 did not reach VO2peak). Reproducibility of VO2peak was high (intraclass correlation coefficient=0.97). CONCLUSIONS: CPET was feasible, effective and safe for community-dwelling older adults, many of whom had multimorbidity and frailty. These data support a broader implementation of CPET to provide important insight into the role of CRF and its underlying determinants in aging and age-related conditions and diseases. Clinical Perspective: What Is New?: Performing cardiopulmonary exercise testing in a community dwelling older adult with multimorbidities or frailty is feasible and exceptionally safe under highly trained exercise physiologists and physician supervision.Reproducibility of VO2peak among community-dwelling older adults with significant clinical complexity was high (intraclass correlation coefficient=0.97).The VO2peak observed was comparable to established normative data for older adults, and adds merit to the limited data collected on VO2peak norms in older adults.What Are the Clinical Implications?: Ventilatory gas collection during clinical cardiac stress testing may be valuable to plan of care in routine management of older adults due to the important role of aerobic fitness on morbidity and mortality.Cardiopulmonary exercise testing can provide insight into the role of cardiorespiratory fitness and its underlying determinants in aging and age-related conditions and diseases.