All-cause mortality and cause-specific death in U.S. long-lived siblings: data from the Long Life Family Study.

BACKGROUND: This study compared the mortality risk of long-lived siblings with the U.S. population average and their spouse controls, and investigated the leading causes of death and the familial effect in death pattern. METHODS: In the Long Life Family Study (LLFS), 1,264 proband siblings (Mean age 90.1, SD 6.4) and 172 spouses (83.8, 7.2) from 511 U.S.-based families were recruited and followed over 12 years. Their survival function was compared with a birth cohort-, baseline age-, sex-, and race-matched pseudo sample from U.S. census data. To examine underlying and contributing causes, we examined in detail 338 deaths with complete death adjudication at the University of Pittsburgh Field Center through the year 2018. A familial effect on survival and death pattern was examined using mixed effect models. RESULTS: The LLFS siblings had better survival than the matched U.S. population average. They also had slightly but not significantly better survival than their spouses' (HR=1.18 [95%CI 0.94-1.49]) after adjusting for age and sex. Age at death ranged from 75-104 years, mean 91.4. The leading causes of death were cardiovascular disease (33.1%), dementia (22.2%), and cancer (10.7%). Mixed effect model shows a significant random effect of family in survival, with adjustment of baseline age and sex. There was no significant familial effect in the underlying cause of death or conditions directly contributing to death among siblings recruited by the University of Pittsburgh Field Center. CONCLUSION: Our findings demonstrate a higher survival in the LLFS siblings than the U.S. census data, with a familial component of survival. We did not find significant correspondence in causes of death between siblings within families.

Serial gait speed measurements over time and dynamic survival prediction in older adults.

BACKGROUND: A one-time gait speed measurement predicts mortality risk. A framework for updating a clinician's mortality risk perception with new information from each clinic visit is needed. We used joint modeling of longitudinal and survival data for dynamic prediction of mortality risk. METHODS: We fit sex-stratified joint models to 20-meter (bi)annual longitudinal gait speed measured every 6 months and 14-year survival data from the Health, Aging and Body Composition Study allowing for non-linear fluctuations of gait speed and controlling for important covariates such as age, recent hospitalization, blood pressure, obesity, and comorbidities. RESULTS: Participants (N = 3048) were 74 years old with gait speed 1.18 m/s. They were 42% Black, and 52% died over 14 years. Higher gait speed of 0.1 m/s was associated with 23% (95% confidence interval or CI = 20-25%) and 25% (CI = 21-28%) reductions in mortality risk in men and women; and a 0.05 m/s annualized slowing (slope) with 31% (CI = 13-51%) increase in men (all p < 0.05), with findings persisting after covariate adjustment. Distant gait speed history over a year prior contributed little for mortality risk prediction with mean change of only 1-2% in 5-year risk. CONCLUSION: The two most recent gait speeds appear sufficient to consider for mortality risk in the present initial analysis. More frequent gait speeds need to be considered in mortality risk prediction before definitive conclusions supporting real-world application.

Medicare Fee-For-Service Spending for Fall Injury and Nonfall Events: The Health, Aging, and Body Composition Study.

Background and Objectives: Fall injuries are prevalent in older adults, yet whether higher spending occurs after nonfracture (NFFI) and fracture is unknown. We examined whether incident fall injuries, including NFFI and fractures, were associated with higher Medicare spending in 12 months after incident events in older adults. Research Design and Methods: The Health, Aging, and Body Composition Study included 1 595 community-dwelling adults (53% women, 37% Black; 76.7 ±â€…2.9 years) with linked Medicare Fee-For-Service (FFS) claims at 2000/01 exam. Incident outpatient and inpatient fall injuries (N = 448) from 2000/01 exam to December 31, 2008 were identified using the first claim with a nonfracture injury diagnosis code with a fall E-code, or a fracture diagnosis code with/without an E-code. Up to 3 participants without fall injuries (N = 1 147) were matched on nonfall events to 448 participants in the fall injury month. We calculated the change in monthly FFS spending in 12 months before versus after index events in both groups. Generalized linear regression with centered outcomes and gamma distributions examined the association of prepost expenditure changes with fall injuries (including NFFI and fractures) adjusting for related covariates. Results: Monthly spending increased after versus before fall injuries (USD$2 261 vs $981), nonfracture (N = 105; USD$2 083 vs $1 277), and fracture (N = 343; USD$2 315 vs $890) injuries (all p < .0001). However, after adjusting for covariates in final models, fall injuries were not significantly associated with larger increases in spending/month versus nonfall events (differential increase: USD$399.58 [95% CI: -USD$44.95 to $844.11]). Fracture prepost change in monthly spending was similar versus NFFI (differential increase: USD$471.93 [95% CI: -USD$21.17 to $965.02]). Discussion and Implications: Although substantial increases occurred after injuries, with fracture and NFFI increasing similarly, changes in monthly spending after fall injury were not different compared to nonfall events. Our results contribute to the understanding of subsequent spending after fall injury that may inform further research on fall injury-related health care spending.

Plasma proteomic signature of human longevity.

The identification of protein targets that exhibit anti-aging clinical potential could inform interventions to lengthen the human health span. Most previous proteomics research has been focused on chronological age instead of longevity. We leveraged two large population-based prospective cohorts with long follow-ups to evaluate the proteomic signature of longevity defined by survival to 90 years of age. Plasma proteomics was measured using a SOMAscan assay in 3067 participants from the Cardiovascular Health Study (discovery cohort) and 4690 participants from the Age Gene/Environment Susceptibility-Reykjavik Study (replication cohort). Logistic regression identified 211 significant proteins in the CHS cohort using a Bonferroni-adjusted threshold, of which 168 were available in the replication cohort and 105 were replicated (corrected p value <0.05). The most significant proteins were GDF-15 and N-terminal pro-BNP in both cohorts. A parsimonious protein-based prediction model was built using 33 proteins selected by LASSO with 10-fold cross-validation and validated using 27 available proteins in the validation cohort. This protein model outperformed a basic model using traditional factors (demographics, height, weight, and smoking) by improving the AUC from 0.658 to 0.748 in the discovery cohort and from 0.755 to 0.802 in the validation cohort. We also found that the associations of 169 out of 211 proteins were partially mediated by physical and/or cognitive function. These findings could contribute to the identification of biomarkers and pathways of aging and potential therapeutic targets to delay aging and age-related diseases.

Association of a Blood-Based Aging Biomarker Index With Death and Chronic Disease: Cardiovascular Health Study.

BACKGROUND: A goal of gerontology is to discover phenotypes that reflect biological aging distinct from disease pathogenesis. Biomarkers that are strongly associated with mortality could be used to define such a phenotype. However, the relation of such an index with multiple chronic conditions warrants further exploration. METHODS: A biomarker index (BI) was constructed in the Cardiovascular Health Study (N = 3 197), with a mean age of 74 years. The BI incorporated circulating levels of new biomarkers, including insulin-like growth factor-1, interleukin-6, amino-terminal pro-B-type natriuretic peptide, cystatin-C, C-reactive protein, tumor necrosis factor-alpha soluble receptor 1, fasting insulin, and fasting glucose, and was built based on their relationships with mortality. Cox proportional hazards models predicting a composite of death and chronic disease involving cardiovascular disease, dementia, and cancer were calculated with 6 years of follow-up. RESULTS: The hazard ratio (HR, 95% CI) for the composite outcome of death or chronic disease per category of BI was 1.65 (1.52, 1.80) and 1.75 (1.58, 1.94) in women and men, respectively. The HR (95% CI) per 5 years of age was 1.57 (1.48, 1.67) and 1.55 (1.44, 1.67) in women and men, respectively. Moreover, BI could attenuate the effect of age on the composite outcome by 16.7% and 22.0% in women and men, respectively. CONCLUSIONS: Biomarker index was significantly and independently associated with a composite outcome of death and chronic disease, and attenuated the effect of age. The BI that is composed of plasma biomarkers may be a practical intermediate phenotype for interventions aiming to modify the course of aging.

Role of Perceived Physical and Mental Fatigability Severity on Prospective, Recurrent, and Injurious Fall Risk in Older Men.

BACKGROUND: Falls occur annually in 25% of adults aged ≥65 years. Fall-related injuries are increasing, highlighting the need to identify modifiable risk factors. METHODS: Role of fatigability on prospective, recurrent, and injurious fall risk was examined in 1 740 men aged 77-101 years in the Osteoporotic Fractures in Men Study. The 10-item Pittsburgh Fatigability Scale measured perceived physical and mental fatigability (0-50/subscale) at Year 14 (2014-16); established cut-points identified men with more severe perceived physical (≥15, 55.7%), more severe mental (≥13, 23.7%) fatigability, or having both (22.8%). Prospective, recurrent (≥2), and injurious falls were captured by triannual questionnaires ≥1 year after fatigability assessment; risk of any fall was estimated with Poisson generalized estimating equations, and likelihood of recurrent/injurious falls with logistic regression. Models adjusted for age, health conditions, and other confounders. RESULTS: Men with more severe physical fatigability had a 20% (p = .03) increased fall risk compared with men with less physical fatigability, with increased odds of recurrent and injurious falls, 37% (p = .04) and 35% (p = .035), respectively. Men with both more severe physical and mental fatigability had a 24% increased risk of a prospective fall (p = .026), and 44% (p = .045) increased odds of recurrent falling compared with men with less severe physical and mental fatigability. Mental fatigability alone was not associated with fall risk. Additional adjustment for previous fall history attenuated associations. CONCLUSIONS: More severe fatigability may be an early indicator to identify men at high risk for falls. Our findings warrant replication in women, as they have higher rates of fatigability and prospective falls.

Lower Leg Power and Grip Strength Are Associated With Increased Fall Injury Risk in Older Men: The Osteoporotic Fractures in Men Study.

BACKGROUND: Past research has not investigated both lower-extremity power and upper-extremity strength in the same fall injury study, particularly nonfracture fall injuries. METHODS: In the Osteoporotic Fractures in Men Study (baseline: N = 5 994; age 73.7 ± 5.9 years; 10.2% non-White), fall injuries (yes/no) were assessed prospectively with questionnaires approximately every 3 years over 9 years. Maximum leg power (Watts) from Nottingham single leg press and maximum grip strength (kg) from handheld dynamometry were assessed at baseline and standardized to kg body weight. Physical performance included gait speed (6-m usual; narrow walk) and chair stands speed. RESULTS: Of men with ≥1/4 follow-ups (N = 5 178; age 73.4 ± 5.7 years), 40.4% (N = 2 090) had ≥1 fall injury. In fully adjusted repeated-measures logistic regressions, lower power/kg and grip strength/kg had higher fall injury risk (trend across quartiles: both p < .0001), with lower quartiles at significantly increased risk versus highest Q4 except for grip strength Q3 versus Q4. Fall injury risk was 19% higher per 1 standard deviation (SD) lower power/kg (95% confidence interval [CI]: 1.12-1.26) and 16% higher per SD lower grip strength/kg (95% CI: 1.10-1.23). In models including both leg power/kg and grip strength/kg, odds ratios (ORs) were similar and independent of each other and physical performance (leg power/kg OR per SD = 1.13, 95% CI: 1.06-1.20; grip strength/kg OR per SD = 1.11, 95% CI: 1.05-1.17). CONCLUSIONS: Lower leg power/kg and grip strength/kg predicted future fall injury risk in older men independent of physical performance. Leg power potentially identifies fall injury risk better than grip strength at higher muscle function, though grip strength may be more suitable in clinical/practice settings.

Effectiveness of a behavioral lifestyle intervention on weight management and mobility improvement in older informal caregivers: a secondary data analysis.

BACKGROUND: Older informal caregivers are prone to sedentary behavior and obesity. With great caregiving burdens and frequent physical and mental distress, older informal caregivers may have low adherence and poor results in behavioral intervention for weight management. This study examined whether overweight or obese older informal caregivers could benefit from a behavioral weight management program as much as non-caregivers. METHODS: The Mobility and Vitality Lifestyle Program (MOVE UP) was a pre-post, community-based, 13-month lifestyle intervention study to help older adults improve physical function performance and lose weight. We identified a subset of informal caregivers (n = 29) and non-caregivers (n = 65) from the MOVE UP participants retrospectively. Changes in lower extremity function, weight, depressive symptoms, and self-efficacy from baseline were compared between caregivers and non-caregivers using paired t-tests and ANCOVA. RESULTS: Older informal caregivers had significantly lower session attendance rates than non-caregivers (67.7% vs 76.8%, P < 0.05), however, both informal caregivers and non-caregivers improved significantly in lower extremity function, weight loss, and self-efficacy in diet (Ps < 0.05). For each outcome, changes from baseline to the 13-month endpoint were the same among informal caregivers and non-caregivers. CONCLUSION: This study provides evidence that older informal caregivers can benefit from behavioral weight management interventions despite the challenge caregiving poses for effective self-care. Future behavioral intervention studies for older informal caregivers should adopt self-monitoring tools and extend the on-site delivery to home-based settings for higher adherence and greater flexibility. TRIAL REGISTRATION: Registered at clinicaltrials.gov (NCT02657239).

Development of a Novel Accelerometry-Based Performance Fatigability Measure for Older Adults.

INTRODUCTION: Efforts to study performance fatigability have been limited because of measurement constrains. Accelerometry and advanced statistical methods may enable us to quantify performance fatigability more granularly via objective detection of performance decline. Thus, we developed the Pittsburgh Performance Fatigability Index (PPFI) using triaxial raw accelerations from wrist-worn accelerometer from two in-laboratory 400-m walks. METHODS: Sixty-three older adults from our cross-sectional study (mean age, 78 yr; 56% women; 88% White) completed fast-paced ( n = 59) and/or usual-paced 400-m walks ( n = 56) with valid accelerometer data. Participants wore ActiGraph GT3X+ accelerometers (The ActiGraph LLC, Pensacola, FL) on nondominant wrist during the walking task. Triaxial raw accelerations from accelerometers were used to compute PPFI, which quantifies percentage of area under the observed gait cadence-versus-time trajectory during a 400-m walk to a hypothetical area that would be produced if the participant sustained maximal cadence throughout the entire walk. RESULTS: Higher PPFI scores (higher score = greater fatigability) correlated with worse physical function, slower chair stands speed and gait speed, worse cardiorespiratory fitness and mobility, and lower leg peak power (| ρ | = 0.36-0.61 from fast-paced and | ρ | = 0.28-0.67 from usual-paced walks, all P < 0.05). PPFI scores from both walks remained associated with chair stands speed, gait speed, fitness, and mobility, after adjustment for sex, age, race, weight, height, and smoking status; PPFI scores from the fast-paced walk were associated with leg peak power. CONCLUSIONS: Our findings revealed that the objective PPFI is a sensitive measure of performance fatigability for older adults and can serve as a risk assessment tool or outcome measure in future studies and clinical practice.

Changes in Objectively Measured Physical Activity Are Associated With Perceived Physical and Mental Fatigability in Older Men.

BACKGROUND: Lower physical activity (PA) is associated with greater perceived fatigability, a person-centered outcome. The association between change in PA and fatigability with advanced age has yet to be established. METHODS: Community-dwelling older men (N = 1 113, age = 84.1 ± 3.9 years at Year 14) had free-living PA assessed using SenseWear Armband prospectively at Year 7 (2007-2009) and Year 14 (2014-2016) of Osteoporotic Fractures in Men Study, a longitudinal cohort established in 2000 (baseline). We categorized percent changes in PA into groups (large decline → large increase) for 4 metrics: step count, light intensity PA (LIPA, metabolic equivalents [METs] >1.5 to <3.0), moderate-to-vigorous PA (MVPA, METs ≥ 3.0), and sedentary behavior (SB, METs ≤ 1.5, excluding sleep). Perceived physical and mental fatigability were measured (Year 14) with the Pittsburgh Fatigability Scale (PFS, higher score = greater fatigability; range = 0-50). Associations between each metric of percent changes in PA and fatigability were examined using linear regression, adjusted for demographics, change in health conditions, and Year 7 step count or total PA (METs > 1.5). RESULTS: Men declined 2 336 ± 2 546 (34%) steps/d, 24 ± 31 (25%) LIPA min/d, 33 ± 58 (19%) MVPA min/d, and increased 40 ± 107 (6%) SB min/d over 7.2 ± 0.7 years. Compared to large decline (% change less than -50%), those that maintained or increased step count had 3-8 points lower PFS Physical scores; those who maintained or increased LIPA and MVPA had 2-3 and 2-4 points lower PFS Physical scores, respectively (all p ≤ .01). Associations were similar, but smaller, for PFS Mental scores. CONCLUSION: Older men who maintained or increased PA had lower fatigability, independent of initial PA. Our findings inform the types and doses of PA that should be targeted to reduce fatigability in older adults.

Digitally generated Trail Making Test data: Analysis using hidden Markov modeling.

The Trail Making Test (TMT) is a neuropsychological test used to assess cognitive dysfunction. The TMT consists of two parts: TMT-A requires connecting numbers 1 to 25 sequentially; TMT-B requires connecting numbers 1 to 12 and letters A to L sequentially, alternating between numbers and letters. We propose using a digitally recorded version of TMT to capture cognitive or physical functions underlying test performance. We analyzed digital versions of TMT-A and -B to derive time metrics and used Bayesian hidden Markov models to extract additional metrics. We correlated these derived metrics with cognitive and physical function scores using regression. On both TMT-A and -B, digital metrics associated with graphomotor processing test scores and gait speed. Digital metrics on TMT-B were additionally associated with episodic memory test scores and grip strength. These metrics provide additional information of cognitive state and can differentiate cognitive and physical factors affecting test performance.

Prospective Associations Between Physical Activity and Perceived Fatigability in Older Men: Differences by Activity Type and Baseline Marital Status.

BACKGROUND: Lower physical activity has been cross-sectionally associated with greater perceived fatigability, defined as self-reported fatigue anchored to activity intensity and duration. The temporality of this relationship, and whether it differs by activity type or marital status, remains unclear. METHODS: In the Osteoporotic Fractures in Men Study (N = 1 759), self-reported total, exercise, and household activity were assessed using the Physical Activity Scale for the Elderly across 7 visits (2000-2016). The Pittsburgh Fatigability Scale (range: 0-50; higher scores = greater fatigability) measured physical (mean = 16.6 ± 9.7) and mental (mean = 7.8 ± 8.3) fatigability at Year 14. Least absolute deviation and linear regression were used to examine associations between baseline and change in activity over 14 years with subsequent fatigability. Models were adjusted for demographic, health, and lifestyle factors. RESULTS: After adjustment, lower baseline (ß= -0.08, 95% confidence interval [CI]: -0.12, -0.04) and greater annual declines in total activity (ß = -0.09, 95% CI: -0.14, -0.05) were prospectively associated with higher Pittsburgh Fatigability Scale (PFS) Physical scores. Associations were similar for mental fatigability (both p < .05). Lower baseline leisure exercise, but not baseline household activity, predicted higher PFS Physical scores (ß = -0.10 vs -0.001). In contrast, greater declines in household activity, but not declines in exercise, were associated with higher PFS Physical scores (ß = -0.09 vs -0.03). Lower baseline household activity predicted higher PFS Mental scores only for unmarried men (ß = -0.15, 95% CI: -0.29, -0.01, interaction p = .019). CONCLUSIONS: Baseline total activity and leisure exercise, and declines in total and household activity, were associated with higher subsequent perceived fatigability in older men. Marital status may mitigate the contribution of household activity to subsequent fatigability.

Peripheral bone structure, geometry, and strength and muscle density as derived from peripheral quantitative computed tomography and mortality among rural south Indian older adults.

Multiple studies have observed a relationship of bone mineral density (BMD) measured by Dual energy X-ray absorptiometry (DXA) and mortality. However, areal BMD (aBMD) measured by DXA is an integrated measure of trabecular and cortical bone and does not measure the geometry of bone. Peripheral Quantitative Computed Tomography (pQCT) provides greater insights on bone structure, geometry and strength. To examine whether higher bone phenotypes and muscle density as measured by pQCT are associated with a lower all-cause mortality, we studied 245 men and 254 women (all age >60) recruited in the Mobility and Independent Living among Elders Study in rural south India. Cox proportional hazards models estimated hazard ratios (HR [95% Confidence Intervals]). After an average follow-up of 5.3 years, 73 men and 50 women died. Among men, trabecular volumetric bone mineral density (vBMD) of radius (HR per SD increase in parameter = 0.59 [0.43, 0.81]) and tibia (0.60[0.45, 0.81]), cortical vBMD of radius (0.61, [0.47, 0.79]) and tibia (0.62, [0.49, 0.79]), cortical thickness of radius (0.55, [0.42, 0.7]) and tibia (0.60, [0.47, 0.77]), polar strength strain index (SSIp) of tibia (0.73 [0.54, 0.98]), endosteal circumference of radius (1.63, [1.25, 2.12]) and tibia (1.54, [1.19, 1.98]) were associated with all-cause mortality. Muscle density (0.67, [0.51, 0.87]) was associated with lower mortality in men. Among women cortical vBMD of radius (0.64, [0.47, 0.87]) and tibia (0.60 [0.45, 0.79]), cortical thickness of radius (0.54, [0.37, 0.79]) and tibia (0.43, [0.30, 0.61]), SSIp of radius (0.70 [0.48,1.01]) and tibia (0.58 [0.37, 0.90]) and endosteal circumference of radius (1.33 [0.97, 1.82]) and tibia (1.83, [1.37, 2.45]) were associated with all-cause mortality. Among men, gait speed mediated the association of muscle density and mortality but there was no mediation for any bone parameters. Conclusion: pQCT bone measures and muscle density were independently associated with mortality among rural south Indian elders.

Relationship Between Personality Measures and Perceived Mental Fatigability.

OBJECTIVE: Examine the association between personality measures and perceived mental fatigability. METHODS: We performed a cross-sectional analysis in N=1670 men, age 84.3±4.1 years. Multivariable linear regression models were used to examine the covariate adjusted association between personality measures (conscientiousness, optimism, goal reengagement, and goal disengagement) and perceived mental fatigability (measured with the validated 10-item Pittsburgh Fatigability Scale, PFS). RESULTS: One standard deviation lower conscientiousness (ß=-0.91, p<.0001) and optimism (ß=-0.63, p<.0001), and higher goal reengagement (ß=0.51, p=.01) scores were independently associated with higher PFS Mental scores adjusted for age, cognitive function, self-reported health status, depressive symptoms, sleep disturbance, physical activity, and goal disengagement. DISCUSSION: Lower conscientiousness, optimism, and higher goal reengagement were linked with more severe perceived mental fatigability in older men. Personality traits may potentially contribute to early risk assessment for fatigability in later life. Future work should be longitudinal in nature and include personality assessments to confirm the temporality of the relationships observed.

Perceived Physical Fatigability Predicts All-Cause Mortality in Older Adults.

BACKGROUND: Perceived physical fatigability is highly prevalent in older adults and associated with mobility decline and other health consequences. We examined the prognostic value of perceived physical fatigability as an independent predictor of risk of death among older adults. METHODS: Participants (N = 2 906), mean age 73.5 [SD, 10.4] years, 54.2% women, 99.7% white enrolled in the Long Life Family Study, were assessed at Visit 2 (2014-2017) with 2.7 [SD, 1.0] years follow-up. The Pittsburgh Fatigability Scale (PFS), a 10-item, self-administered validated questionnaire (score range 0-50, higher = greater fatigability) measured perceived physical fatigability at Visit 2. Deaths post-Visit 2 through December 31, 2019 were identified by family members notifying field centers, reporting during another family member's annual phone follow-up, an obituary, or Civil Registration System (Denmark). We censored all other participants at their last contact. Cox proportional hazard models predicted mortality by fatigability severity, adjusted for family relatedness and other covariates. RESULTS: Age-adjusted PFS Physical scores were higher for those who died (19.1 [SE, 0.8]) compared with alive (12.2, [SE, 0.4]) overall, as well as across age strata (p < .001), except for those 60-69 years (p = .79). Participants with the most severe fatigability (PFS Physical scores ≥ 25) were over twice as likely to die (hazard ratio, 2.33 [95% CI, 1.65-3.28]) compared with those who had less severe fatigability (PFS Physical scores < 25) after adjustment. CONCLUSIONS: Our work underscores the utility of the PFS as a novel patient-reported prognostic indicator of phenotypic aging that captures both overt and underlying disease burden that predicts death.

Weight Loss through Lifestyle Intervention Improves Mobility in Older Adults.

BACKGROUND AND OBJECTIVES: The high prevalence of overweight or obesity in older adults is a public health concern because obesity affects health, including the risk of mobility disability. RESEARCH DESIGN AND METHODS: The Mobility and Vitality Lifestyle Program, delivered by community health workers (CHWs), enrolled 303 community-dwelling adults to assess the impact of a 32-session behavioral weight management intervention. Participants completed the program at 26 sites led by 22 CHWs. Participation was limited to people aged 60-75 who had a body mass index (BMI) of 27-45 kg/m2. The primary outcome was the performance on the Short Physical Performance Battery (SPPB) over 12 months. RESULTS: Participants were aged 67.7 (SD 4.1) and mostly female (87%); 22.7% were racial minorities. The mean (SD) BMI at baseline was 34.7 (4.7). Participants attended a median of 24 of 32 sessions; 240 (80.3%) completed the 9- or 13-month outcome assessment. Median weight loss in the sample was 5% of baseline body weight. SPPB total scores improved by +0.31 units (p < .006), gait speed by +0.04 m/s (p < .0001), and time to complete chair stands by -0.95 s (p < .0001). Weight loss of at least 5% was associated with a gain of +0.73 in SPPB scores. Increases in activity (by self-report or device) were not independently associated with SPPB outcomes but did reduce the effect of weight loss. DISCUSSION AND IMPLICATIONS: Promoting weight management in a community group setting may be an effective strategy for reducing the risk of disability in older adults.

Perceived physical fatigability improves after an exercise intervention among breast cancer survivors: a randomized clinical trial.

BACKGROUND: Among breast cancer populations, exercise interventions resulted in positive but relatively small improvements on fatigue, which may be due to insensitive measures of global fatigue. Perceived fatigability-whole-body tiredness anchored to standardized tasks/activities of a specific intensity and duration-may help to detect effective exercise interventions reducing fatigue in oncology. We examined whether perceived physical fatigability improved after an exercise intervention. METHODS: This single center randomized clinical trial of 49 breast cancer survivors was conducted from 2015 to 2017, among which 41 participants (22 = exercise, 19 = control) completed the trial and reported their perceived physical fatigability at the first (Visit 1) and the last visit (Visit 3) over 6-14 weeks. Perceived physical fatigability was measured using the 10-item, self-administered Pittsburgh Fatigability Scale (PFS) scored 0-50. The mean differences of perceived physical fatigability between Visit 3 and Visit 1 were computed and compared by intervention groups using two sample t test. RESULTS: Among the 41 women in the study (mean age 54.9 ± 9.8 years; 80% white), sociodemographic, clinical characteristics and baseline fatigue level were similar by intervention groups, except for antiestrogen use. Post-intervention changes (mean ∆ ± SE) of PFS Physical scores were greater in the exercise group (- 4.4 ± 1.4; - 22.5%) than the control group (0.2 ± 1.4; + 1.0%) (p = .022). CONCLUSION: The PFS captured a reduction in fatigue after the exercise intervention among breast cancer survivors. These findings aid mounting efforts to reduce fatigue in oncology by introducing a more sensitive instrument to measure perceived physical fatigability to better evaluate patient-reported outcomes in future cancer trials. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02770781.

Association of fatigue, inflammation, and physical activity on gait speed: the Long Life Family Study.

BACKGROUND: Fatigue, inflammation, and physical activity (PA) are all independently associated with gait speed, but their directionality is not fully elucidated. AIMS: Evaluate the bidirectional associations amongst fatigue, inflammation, and PA on gait speed. METHODS: This cross sectional study included probands (n = 1280, aged 49-105) and offspring (n = 2772, aged 24-88) in the Long Life Family Study. We assessed gait speed, fatigue with the question "I could not get going", inflammation using fasting interleukin-6 (IL-6) and high sensitivity C-reactive protein (CRP), and self-reported PA as walking frequency in the past two weeks. The two generations were examined separately using linear mixed modeling. RESULTS: Lower fatigue, lower IL-6, and greater PA were all associated with faster gait speed in both generations (all p < 0.05); lower CRP was only associated with faster gait speed in the offspring. PA explained the association of fatigue and gait speed via a 16.1% (95% CI 9.7%, 26.7%) attenuation of the direct associations for the probands and 9.9% (95% CI 6.3%, 18.8%) in the offspring. In addition, IL-6 explained more of the association of fatigue and gait speed than the association between PA and gait speed, via a 14.9% (95% CI 9.2%, 23.4%) attenuation of the direct association in the offspring only. DISCUSSION: Results revealed a potential directionality from fatigue to IL-6 to PA that may lead to faster gait speed. Future work should examine these relationships longitudinally to establish temporality and causality. CONCLUSIONS: Our findings support a signal that lowering fatigue and inflammation and increasing physical activity may delay functional decline.

Metabolic Syndrome Trajectories and Objective Physical Performance in Mid-to-Early Late Life: The Study of Women's Health Across the Nation (SWAN).

BACKGROUND: Little is known about how adverse, midlife metabolic profiles affect future physical functioning. We hypothesized that a higher number of midlife metabolic syndrome (MetS) components are associated with poorer physical performance in early old age for multiethnic women. METHODS: MetS status from 1996 to 2011 (8 visits) and objective physical performance in 2015/2016 (Short Physical Performance Battery [SPPB; 0-12], 40-foot walk [meter/second], 4-meter gait speed [meter/second], chair stands [seconds], stair climb [seconds]) were assessed in the Study of Women's Health Across the Nation (SWAN; n = 1722; age 65.4 ± 2.7 years; 26.9% African American, 10.1% Chinese, 9.8% Japanese, 5.5% Hispanic). Poisson latent class growth modeling identified MetS component trajectory groups: none (23.9%), 1 = low-MetS (28.7%), 2 = mid-MetS (30.9%), and ≥3 = high-MetS (16.5%). Adjusted linear regression related MetS groups to physical performance outcomes. RESULTS: High-MetS versus none had higher body mass index, pain, financial strain, and lower physical activity and self-reported health (p < .0001). Compared with White, African American and Hispanic women were more likely to be in the high-MetS groups and had worse physical functioning along with Chinese women (SPPB, chair stand, stair climb, and gait speed-not Hispanic). After adjustments, high-MetS versus none demonstrated significantly worse 40-ft walk (ß: -0.08; 95% CI: -0.13, -0.03), gait speed (ß: -0.09; 95% CI: -0.15, -0.02), SPPB (ß: -0.79; 95% CI: -1.15, -0.44), and chair stands (ß: 0.69; 95% CI: 0.09, 1.28), but no difference in stair climb. CONCLUSIONS: Midlife MetS groups were related to poor physical performance in early old age multiethnic women. Midlife management of metabolic function may improve physical performance later in life.