Longitudinal characteristics of physical frailty and its components in men and women post hip fracture.

BACKGROUND: Frailty is an important geriatric syndrome predicting adverse health outcomes in older adults. However, the longitudinal characteristics of frailty components in post-hip fracture patients are less understood. Adopting the Fried frailty definition, we examined the longitudinal trends and sex trajectory differences in frailty and its components over 1 year post-fracture. METHODS: Three hundred and twenty-seven hip fracture patients (162 men and 165 women with mean age 80.1 and 81.5) from Baltimore Hip Studies 7th cohort with measurements at 22 days after admission, and months 2, 6, and 12 post-fracture were analyzed. Frailty components included: grip strength, gait speed, weight, total energy expenditure, and exhaustion. Longitudinal analysis used mixed effect models. RESULTS: At baseline, men were sicker with worse cognitive status, and had higher weight and grip strength, but lower total energy expenditure than women (p < 0.001). The prevalence of frailty was 31.5%, 30.2%, and 28.2% at months 2, 6, and 12 respectively, showing no longitudinal trends or sex differences. However, its components showed substantial recovery trends over the post-fracture year after confounding adjustments, including increasing gait speed, reducing risk of exhaustion, and stabilized weight loss and energy expenditure over time. Particularly, while men's grip strength tended to remain stable over first year post surgery within patients, women's grip strength reduced significantly over time within patients. On average over time within patients, women were more active with higher energy expenditures but lower grip strength and weight than men. CONCLUSION: Significant recovery trends and sex differences were observed in frailty components during first year post-fracture. Overall frailty status did not show those trends over months 2-12 since a summary measure might obscure changes in components. Therefore, frailty components provided important multi-dimensional information on the complex recovery process of patients, indicating targets for intervention beyond the global binary measure of frailty.

Sex-specific 25-hydroxyvitamin D threshold concentrations for functional outcomes in older adults: PRoject on Optimal VItamin D in Older adults (PROVIDO).

BACKGROUND: Threshold serum 25-hydroxyvitamin D [25(OH)D] concentrations for extraskeletal outcomes are uncertain and could differ from recommendations (20-30 ng/mL) for skeletal health. OBJECTIVES: We aimed to identify and validate sex-specific threshold 25(OH)D concentrations for older adults' physical function. METHODS: Using 5 large prospective, population-based studies-Age, Gene/Environment Susceptibility-Reykjavik (n = 4858, Iceland); Health, Aging, and Body Composition (n = 2494, United States); Invecchiare in Chianti (n = 873, Italy); Osteoporotic Fractures in Men (n = 2301, United States); and Study of Osteoporotic Fractures (n = 5862, United States)-we assessed 16,388 community-dwelling adults (10,376 women, 6012 men) aged ≥65 y. We analyzed 25(OH)D concentrations with the primary outcome (incident slow gait: women <0.8 m/s; men <0.825 m/s) and secondary outcomes (gait speed, incident self-reported mobility, and stair climb impairment) at median 3.0-y follow-up. We identified sex-specific 25(OH)D thresholds that best discriminated incident slow gait using machine learning in training data (2/3 cohort-stratified random sample) and validated using the remaining (validation) data and secondary outcomes. RESULTS: Mean age in the cohorts ranged from 74.4 to 76.5 y in women and from 73.3 to 76.6 y in men. Overall, 1112/6123 women (18.2%) and 494/3937 men (12.5%) experienced incident slow gait, 1098/7011 women (15.7%) and 474/3962 men (12.0%) experienced incident mobility impairment, and 1044/6941 women (15.0%) and 432/3993 men (10.8%) experienced incident stair climb impairment. Slow gait was best discriminated by 25(OH)D <24.0 ng/mL compared with 25(OH)D ≥24.0 ng/mL in women (RR: 1.29; 95% CI: 1.10, 1.50) and 25(OH)D <21.0 ng/mL compared with 25(OH)D ≥21.0 ng/mL in men (RR: 1.43; 95% CI: 1.01, 2.02). Most associations between 25(OH)D and secondary outcomes were modest; estimates were similar between validation and training datasets. CONCLUSIONS: Empirically identified and validated sex-specific threshold 25(OH)D concentrations for physical function for older adults, 24.0 ng/mL for women and 21.0 ng/mL for men, may inform candidate reference concentrations or the design of vitamin D intervention trials.

The Relationship of Lean Body Mass With Aging to the Development of Diabetes.

CONTEXT: Older adults have the greatest burden of diabetes; however, the contribution of age-related muscle loss to its development remains unclear. OBJECTIVE: We assessed the relationship of lean body mass with aging to incident diabetes in community-dwelling adults. DESIGN AND SETTING: We studied participants in the Baltimore Longitudinal Study of Aging with median follow-up of 7 years (range 1-16). Cox proportional hazard models with age as the time scale were used. Time-dependent lean body mass measures were updated at each follow-up visit available. PARTICIPANTS: Participants included 871 men and 984 women without diabetes who had  ≥ 1 assessment of body composition using dual x-ray absorptiometry. MAIN OUTCOMES: Incident diabetes, defined as self-reported history and use of glucose-lowering medications; or fasting plasma glucose ≥ 126 mg/dL and 2-hour oral glucose tolerance test glucose ≥ 200 mg/dL either at the same visit or 2 consecutive visits. RESULTS: The baseline mean [standard deviation] age was 58.9  [17.3] years. Men and women with a higher percentage of total lean body mass had lower fasting and 2-hour glucose levels, and less prediabetes (all P < 0.01). Among men, comparing highest versus lowest quartiles, percentage of total lean body mass (hazard ratio [HR],  0.46; 95% confidence interval, 0.22-0.97), percentage leg lean mass (HR, 0.38; 0.15-0.96), and lean-to-fat mass ratio (HR, 0.39; 0.17-0.89) were inversely associated with incident diabetes after accounting for race and attenuated after adjustment for height and weight. Conversely, absolute total lean body mass was positively associated with incident diabetes among women, with similar trends in men. No associations were observed with muscle strength or quality. CONCLUSIONS: Relatively lower lean body mass with aging is associated with incident diabetes in men and partially related to anthropometrics, but not so in women.

Comparing Longitudinal Sarcopenia Trends by Definitions Across Men and Women After Hip Fracture.

OBJECTIVES: While sarcopenia is prevalent after hip fracture in the acute postfracture period, little is known about the prevalence after discharge. This study assessed longitudinal trends in sarcopenia prevalence over 12 months after hip fracture using three different operational definitions. DESIGN: Prospective observational study. SETTING: Baltimore Hip Studies seventh cohort. PARTICIPANTS: A total of 82 men and 78 women, aged 65 years and older, with surgical repair of a nonpathological hip fracture. MEASUREMENTS: Baseline assessment included a dual-energy X-ray absorptiometry scan and interview. Follow-up assessments, which additionally included performance measures, occurred 2, 6, and 12 months after admission. Using these measures, three sarcopenia definitions were assessed over the year following hip fracture: European Working Group on Sarcopenia in Older Persons (EWGSOP), International Working Group on Sarcopenia (IWGS), and Foundation for the National Institutes of Health (FNIH). RESULTS: EWGSOP and IWGS provided the highest prevalence of sarcopenia (62%-69% in men, 42%-62% in women), while prevalence by FNIH was much lower for men (15%-19%) and women (5%-12%). For both men and women, the agreement between EWGSOP and IWGS definitions was excellent, and FNIH showed poor agreement with them, supported by various statistical measures across first-year follow-up. Prevalence was stable over time in men by all definitions, while the prevalence in women by FNIH was lowest at 2 months, significantly increased at 6 months (P = .03), and remained higher at 12 months. Whether sarcopenia prevalence differed significantly by sex varied by time point and definition; however, when different, men had a higher prevalence than women (P < .05). While some participants recovered from sarcopenia over time, some also became newly sarcopenic. CONCLUSION: The prevalence of sarcopenia after fracture differed greatly for EWGSOP and IWGS compared to FNIH. Overall, there appeared to be no reduction in sarcopenia over the year after hip fracture, regardless of definition. Future research should examine the relationship between sarcopenia prevalence and functional recovery. J Am Geriatr Soc 68:1537-1544, 2020.

The Roles of Body Composition and Specific Strength in the Relationship Between Race and Physical Performance in Older Adults.

BACKGROUND: Socioeconomics may explain black-white differences in physical performance; few studies examine racial differences among socioeconomically similar groups. Performance is also affected by body composition and specific strength, which differ by race. We assessed whether racial differences in physical performance exist among older adults with high education and similar income and whether body composition and specific strength attenuate observed differences. METHODS: Cross-sectional analysis of 536 men (18% black) and 576 women (28% black) aged more than 60 years from the Baltimore Longitudinal Study of Aging. Body composition was evaluated using dual-energy x-ray absorptiometry. Specific strength was assessed by quadricep peak torque divided by height-normalized thigh cross-sectional area and grip strength divided by body mass index-normalized appendicular lean mass. Physical performance was assessed using usual gait speed and fast 400 m walk time. Sex-stratified linear regression models, adjusted for age, height, education, and recent income, determined whether body composition or specific strength attenuated associations between race and physical performance. RESULTS: Blacks were younger, with higher weight and appendicular lean mass. Black women had higher percent fat and specific strength. In both sexes, blacks had poorer physical performance after adjustment for socioeconomic factors. In women, neither body composition nor specific strength altered the association with gait speed. In men, neither body composition nor specific strength attenuated racial differences in either performance measure. CONCLUSIONS: Poorer physical performance among black compared to white older adults persists among persons with high education and similar income and cannot generally be attributed to differences in body composition or specific strength.

Changes in knee extension peak torque and body composition and their relationship with change in gait speed.

BACKGROUND: Slow gait speed is a powerful predictor of disability in activities of daily living and mortality. Muscle strength and body composition change over time, but their changes differ by sex. How these parameters jointly affect gait speed decline is unknown. Understanding this association could help develop and evaluate the sex-specific effects of lifestyle interventions to delay gait speed decline in older adults. We assessed whether changes in strength (Δstrength), appendicular lean mass (ΔALM), and fat mass (Δfat) jointly relate to change in gait speed and whether the association differs by sex. METHODS: The analytic sample comprised 575 women and 539 men aged 22-95 years enrolled in the Baltimore Longitudinal Study of Aging. Mean follow-up was 4.0 years. Measures included isometric knee extension strength, dual-energy X-ray absorptiometry-assessed ALM and fat mass, and gait speed from the 400 m fast pace walk. Sex-specific linear mixed models were adjusted for follow-up time and baseline age, race, height, ALM, fat mass, peak torque, and gait speed. We also included second-order interaction terms of the key predictive variables (e.g. Δstrength × ΔALM). To interpret the interactions, we estimated average gait declines using the 25th or 75th percentile of the two significant predictive variables and then assessed which condition relates to larger decline in gait speed. RESULTS: In both sexes, independent of ΔALM and Δfat, larger decline in strength significantly related to larger decline in gait speed (P = 0.01 for both sexes). In men, interactions between Δstrength × ΔALM and Δfat by ΔALM were associated with change in gait speed; men with greater declines in both muscle strength and ALM or greater declines in both ALM and fat have steeper gait speed decline. In contrast, in women, the interaction between Δfat and ΔALM was associated with change in gait speed; women with an increase in fat mass combined with less decline in ALM have steeper gait speed decline. CONCLUSIONS: While change in strength affects change in gait speed in both sexes, the effects of body composition change differ by sex. Dual-energy X-ray absorptiometry-based estimates of lean mass may be confounded by intramuscular fat. Future studies should examine sex-specific combined effects of change in strength and body composition on mobility using multiple techniques to measure body composition. Intervention studies should consider testing sex-specific interventions on body composition.

Association Between Adiposity and Perceived Physical Fatigability in Mid- to Late Life.

OBJECTIVE: This study aimed to compare and contrast the associations between measures of adiposity and fat distribution and perceived fatigability among well-functioning individuals in mid- to late life. METHODS: In 1,054 adults (70.4 ± 12.4 years, 52% female), adiposity was measured as BMI, percent fat (dual-energy x-ray absorptiometry), waist and hip circumferences, and waist to height ratio. In a subset of 383 participants, visceral fat was measured. Perceived fatigability was evaluated after a 5-minute treadmill walk (1.5 mph) using the Borg rating of perceived exertion (range, 6-20). Associations between adiposity measures and perceived fatigability were assessed using regression models adjusting for age, sex, race, smoking, and comorbidities. RESULTS: All adiposity measures, except subcutaneous fat, were positively associated with perceived fatigability after adjustment (P < 0.05 for all). Standardized coefficients indicated that BMI, hip circumference, and visceral fat had the strongest associations with fatigability. Associations between BMI and fatigability were present only among those above the threshold for overweight and strongest in those aged ≥ 65 years. Moreover, BMI was associated with fatigability only among participants with higher waist circumference. CONCLUSIONS: Measures of adiposity, particularly central adiposity, are strongly associated with fatigability, suggesting that weight management may be an effective target for curbing fatigability and maintaining quality of life with aging.

Walking speed decline in older adults is associated with elevated pro-BDNF in plasma extracellular vesicles.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is produced by cleavage of proBDNF, and BDNF and proBDNF may play antagonistic roles in nervous system development, learning, memory and neuronal stress resistance. BDNF and proBDNF are present in blood, but the origin and relative contributions of soluble and extracellular vesicle (EV)-associated levels are unknown. METHODS: In this study we used validated immunoassays to measure proBDNF and BDNF levels in plasma, total plasma EVs and a subpopulation of EVs enriched for neuronal origin (expressing the neuronal marker L1CAM) in 150 Baltimore Longitudinal Study of Aging participants with and without decline in walking speed (reflecting aging-associated motor decline). RESULTS: Levels of BDNF and proBDNF were highest in L1CAM+ EVs. Participants with walking speed decline had higher levels of proBDNF in L1CAM+ EVs compared to non-decliners, but no differences in proBDNF levels in plasma and total EV. CONCLUSIONS: Our findings suggest that levels of proBDNF and BDNF in circulating L1CAM+ EVs might be used as biomarkers for conditions involving altered BDNF signaling.

Early body composition, but not body mass, is associated with future accelerated decline in muscle quality.

BACKGROUND: Muscle quality (MQ) or strength-to-mass ratio declines with aging, but the rate of MQ change with aging is highly heterogeneous across individuals. The identification of risk factors for accelerated MQ decline may offer clues to identity the underpinning physiological mechanisms and indicate targets for prevention and treatment. Using data from the Baltimore Longitudinal Study of Aging, we tested whether measures of body mass and body composition are associated with differential rates of changes in MQ with aging. METHODS: Participants included 511 men and women, aged 50 years or older, followed for an average of 4 years (range: 1-8). MQ was operationalized as ratio between knee-extension isokinetic strength and CT-thigh muscle cross-sectional area. Predictors included body mass and body composition measures: weight (kg), body mass index (BMI, kg/m2 ), dual-energy x-ray absorptiometry-measured total body fat mass (TFM, kg) and lean mass (TLM, kg), and body fatness (TFM/weight). Covariates were baseline age, sex, race, and body height. RESULTS: Muscle quality showed a significant linear decline over the time of the follow up (average rate of decline 0.02 Nm/cm2 per year, P < .001). Independent of covariates, neither baseline body weight (P = .756) nor BMI (P = .777) was predictive of longitudinal rate of decline in MQ. Instead, higher TFM and lower TLM at baseline predicted steeper longitudinal decline in MQ (P = .036 and P < .001, respectively). In particular, participants with both high TFM and low TLM at baseline experienced the most dramatic decline compared with those with low TFM and high TLM (about 3% per year vs. 0.5% per year, respectively). Participants in the higher tertile of baseline body fatness presented a significantly faster decline of MQ than the rest of the population (P = .021). Similar results were observed when body mass, TFM, and TLM were modeled as time-dependent predictors. CONCLUSIONS: Body composition, but not weight nor BMI, is associated with future MQ decline, suggesting that preventive strategies aimed at maintaining good MQ with aging should specifically target body composition features.

Cognitive Differences between Men and Women who Fracture their Hip and Impact on Six-Month Survival.

OBJECTIVES: There is limited research in cognition and its relationship to mortality after hip fracture among men compared to women. Therefore, the goals of this study were to: (1) compare men and women who fractured their hip on cognition after hospital discharge, and (2) examine the impact of cognition on the differential risk of 6-month mortality between men and women post fracture. DESIGN: Prospective cohort study. SETTING: Eight hospitals in Baltimore, Maryland. PARTICIPANTS: Frequency matched 168 male and 171 female hip fracture patients, ages 65 or older, living in the community before fracture. MEASUREMENTS: Cognition assed by Modified Mini-Mental State Examination (3MS, and derived MMSE score), Hooper Visual Organization test (HVOT), and Trail-making test (Trails A & B) within 22 days of hospital admission, and 6-month mortality. RESULTS: Men had more impaired cognitive scores on 3MS, MMSE, HVOT, and Trails A (P < .05) at baseline. These statistically significant differences between men and women remained on MMSE and HVOT after controlling for pre-fracture dementia, in-hospital delirium, age, education, race, and comorbidity. Men had higher 6-month mortality rates (HR = 4.4, P < .001). Cognitive measures were also significantly associated with mortality, including 3MS, HVOT, and Trails B. Among the cognitive measures, higher 3MS was most protective for mortality (HR = 0.98, P < .001), both unadjusted and adjusted for other cognitive scales, comorbidity, delirium, and pre-existing dementia. The highest mortality was among men with 3MS<78, with 26.3% dying within 6 months. The effects of cognition on mortality did not differ by sex. CONCLUSION: Men display greater levels of cognitive impairment within the first 22 days of hip fracture than women, and cognitive limitations increase the risk of mortality in both men and women.

Agreement and Predictive Validity Using Less-Conservative Foundation for the National Institutes of Health Sarcopenia Project Weakness Cutpoints.

OBJECTIVES: To derive lean mass cutpoints based on a less-conservative Foundation for the National Institutes of Health (FNIH) Sarcopenia Project Weakness cutpoint for grip strength (WeakI ) and to assess their agreement with European Working Group on Sarcopenia in Older People (EWGSOP) and prediction of incident slow walking and mortality. DESIGN: Longitudinal analysis. SETTING: Baltimore Longitudinal Study of Aging. PARTICIPANTS: Individuals aged 65 and older (287 men, 258 women) with 2 to 10 years of follow-up. MEASUREMENTS: Weakness was determined according to handgrip strength using a hand dynamometer, appendicular lean mass (ALM) using dual-energy X-ray absorptiometry, and walking speed according to 6-m usual pace walk speed. Analyses were performed using classification and regression tree analysis, Cohen's kappa, and Cox models. RESULTS: Cutpoints derived from WeakI for ALM (ALMI ) were less than 21.4 kg in men and less than 14.1 kg in women and for ALM adjusted for body mass index (ALM/BMII ) were less than 0.725 in men and less than 0.591 in women. Kappas with EWGSOP were 0.65 for men and 0.75 for women for ALMI and 0.34 for men and 0.47 for women for ALM/BMII . Men with WeakI + ALMI were twice as likely to develop slow walking as those not weak with normal ALMI (Hazard ratio (HR) = 2.44, 95% confidence interval (CI) = 1.02-5.82). Under EWGSOP, men with weakness and low RALM were almost 3 times as likely to develop slow walking as those not weak with normal RALM (HR = 2.91, 95% CI = 1.11-7.62). Neither approach predicted incident slow walking in women. CONCLUSION: The ALMI cutpoints agree with EWGSOP and predict slow walking in men. Future studies should explore sex differences in the relationship between body composition and physical function and the effect of change in muscle mass on muscle strength and physical function.

Basal body temperature as a biomarker of healthy aging.

Scattered evidence indicates that a lower basal body temperature may be associated with prolonged health span, yet few studies have directly evaluated this relationship. We examined cross-sectional and longitudinal associations between early morning oral temperature (95.0-98.6 °F) and usual gait speed, endurance walk performance, fatigability, and grip strength in 762 non-frail men (52 %) and women aged 65-89 years participating in the Baltimore Longitudinal Study of Aging. Since excessive adiposity (body mass index ≥35 kg/m2 or waist-to-height ratio ≥0.62) may alter temperature set point, associations were also examined within adiposity strata. Overall, controlling for age, race, sex, height, exercise, and adiposity, lower temperature was associated with faster gait speed, less time to walk 400 m quickly, and lower perceived exertion following 5-min of walking at 0.67 m/s (all p ≤ 0.02). In the non-adipose (N = 662), these associations were more robust (all p ≤ 0.006). Direction of association was reversed in the adipose (N = 100), but none attained significance (all p > 0.22). Over 2.2 years, basal temperature was not associated with functional change in the overall population or non-adipose. Among the adipose, lower baseline temperature was associated with greater decline in endurance walking performance (p = 0.006). In longitudinal analyses predicting future functional performance, low temperature in the non-adipose was associated with faster gait speed (p = 0.021) and less time to walk 400 m quickly (p = 0.003), whereas in the adipose, lower temperature was associated with slower gait speed (p = 0.05) and more time to walk 400 m (p = 0.008). In older adults, lower basal body temperature appears to be associated with healthy aging in the absence of excessive adiposity.

Cross-Sectional and Longitudinal Associations Between Adiposity and Walking Endurance in Adults Age 60-79.

BACKGROUND: The impact of excess weight on current and future walking endurance in nondisabled persons is unclear. This study examines the association between obesity and walking endurance among nondisabled persons both in late mid-life and early old age. METHODS: Participants in the Baltimore Longitudinal Study of Aging aged 60-79 years (n = 406) who reported no walking limitations, and completed a 400-meter walk "as quickly as possible" without lower-extremity pain, and had a follow-up assessment within 1.7-4.2 years. Adiposity was assessed by weight, body mass index (BMI), BMI category, and percent fat mass by DXA. RESULTS: Adjusting for age, sex, race, height, and physical activity, all adiposity measures were cross-sectionally associated with slower 400 meter time in both 60-69 and 70 to 79-year-olds (weight: ß = 1.0 and 1.2; BMI: ß = 2.8 and 3.6; and percent fat mass: ß = 2.0 and 2.0, respectively, all p < .001). With additional adjustment for initial 400-meter performance and follow-up time, in 60- to 69-year-olds, change in 400-meter time (positive ß indicates decline) was associated with all adiposity measures (weight: ß = 0.4; BMI: ß = 1.0; and percent fat mass: ß = 0.5; all p ≤ .05) but not in the older group (weight: ß = -0.4; BMI: ß = -1.2; and percent fat mass: ß = -0.2; all p ≥ .17). CONCLUSION: Excess weight and adiposity were associated with worse walking endurance in nondisabled persons aged 60-79 years and predicted accelerated decline in endurance in late mid-life adults. Weight management for mobility independence may be best targeted in obese persons approaching traditional retirement age.

Age-Related Changes in the Anatomy of Language Regions in Autism Spectrum Disorder.

Impairments in language and communication are core features of autism spectrum disorder (ASD). The anatomy of critical language areas has been studied in ASD with inconsistent findings. We used MRI to measure gray matter volume and asymmetry of Heschl's gyrus, planum temporale, pars triangularis, and pars opercularis in 40 children and adolescents with ASD and 40 typically developing individuals, each divided into younger (7-11 years) and older (12-19 years) cohorts. The older group had larger left planum temporale volume and stronger leftward asymmetry than the younger group, regardless of diagnosis. The pars triangularis and opercularis together were larger in ASD than controls. Correlations between frontal language areas with language and symptom severity scores were significant in younger ASD children. Results suggest similar developmental changes in planum temporale anatomy in both groups, but group differences in pars triangularis and opercularis that may be related to language abilities and autism symptom severity.