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.

Bone Mineral Density During and After Lactation: A Comparison of African American and Caucasian Women.

During lactation, changes in maternal calcium metabolism are necessary to provide adequate calcium for newborn skeletal development. The calcium in milk is derived from the maternal skeleton through a process thought to be mediated by the actions of parathyroid hormone-related protein (PTHrP) in combination with decreased circulating estrogen concentrations. After weaning, bone lost during lactation is rapidly regained. Most studies of bone metabolism in lactating women have been performed in Caucasian subjects. There are well-documented differences between African American (AA) and Caucasian (C) bone metabolism, including higher bone mineral density (BMD), lower risk of fracture, lower 25-hydroxyvitamin D (25(OH) D), and higher PTH in AA compared to C. In this prospective paired cohort study, BMD and markers of bone turnover were compared in self-identified AA and C mothers during lactation and after weaning. BMD decreased in both AA and C women during lactation, with similar decreases at the lumbar spine (LS) and greater bone loss in the C group at the femoral neck (FN) and total hip (TH), demonstrating that AA are not resistant to PTHrP during lactation. BMD recovery compared to the 2 week postpartum baseline was observed 6 months after weaning, though the C group did not have complete recovery at the FN. Increases in markers of bone formation and resorption during lactation were similar in AA and C. C-terminal telopeptide (CTX) decreased to 30% below post-pregnancy baseline in both groups 6 months after weaning, while procollagen type 1 N-terminal (P1NP) returned to baseline in the AA group and fell to below baseline in the C group. Further investigation is required to determine impacts on long term bone health for women who do not fully recover BMD before a subsequent pregnancy.

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.

The Association Between Severity of Radiographic Knee OA and Recurrent Falls in Middle and Older Aged Adults: The Osteoarthritis Initiative.

BACKGROUND: Knee osteoarthritis (KOA) is the most prevalent type of OA and a leading cause of disability in the United States. Falls are a major public health concern in older adults. Our aim was to examine how the severity of radiographic KOA affects recurrent falls in a cohort of middle-aged and older individuals enrolled in the Osteoarthritis Initiative. METHODS: About 3 972 participants, mean age of 63 years, 58% female were included. Participants were divided into 5 mutually exclusive groups based on their worst Kellgren-Lawrence grade of radiographic KOA from annual x-rays from baseline to 36 months. Generalized estimating equations for repeated logistic regression were used to model the association between KOA severity and the likelihood of recurrent falls (≥2 falls/year) over 5 years of follow-up (>36 to 96 months). RESULTS: Older adults (≥age 65) with KOA were at higher odds of recurrent falls in comparison to individuals without KOA in multivariate models (possible OA odds ratio [OR] = 2.22, 95% CI = 1.09-4.52; mild OA OR = 2.48, 95% CI = 1.34-4.62; unilateral moderate-severe OA OR = 2.84, 95% CI = 1.47-5.50; bilateral moderate-severe OA OR = 2.52, 95% CI = 1.13-5.62). Middle-aged adults (aged 45-64) with KOA did not have increased odds of recurrent falls in comparison to those without KOA except for possible KOA (OR = 1.86, 95% CI = 1.01-2.78; KOA severity × Age interaction = 0.025). CONCLUSION: Older adults with radiographic evidence of KOA have an increased likelihood of experiencing recurrent falls in comparison to those without KOA independent of established risk factors. Our results suggest that fall prevention efforts should include older adults with all stages of KOA.

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.

Alzheimer's disease as an autoimmune disorder of innate immunity endogenously modulated by tryptophan metabolites.

Introduction: Alzheimer's disease (AD) is characterized by neurotoxic immuno-inflammation concomitant with cytotoxic oligomerization of amyloid beta (Aß) and tau, culminating in concurrent, interdependent immunopathic and proteopathic pathogeneses. Methods: We performed a comprehensive series of in silico, in vitro, and in vivo studies explicitly evaluating the atomistic-molecular mechanisms of cytokine-mediated and Aß-mediated neurotoxicities in AD.  Next, 471 new chemical entities were designed and synthesized to probe the pathways identified by these molecular mechanism studies and to provide prototypic starting points in the development of small-molecule therapeutics for AD. Results: In response to various stimuli (e.g., infection, trauma, ischemia, air pollution, depression), Aß is released as an early responder immunopeptide triggering an innate immunity cascade in which Aß exhibits both immunomodulatory and antimicrobial properties (whether bacteria are present, or not), resulting in a misdirected attack upon "self" neurons, arising from analogous electronegative surface topologies between neurons and bacteria, and rendering them similarly susceptible to membrane-penetrating attack by antimicrobial peptides (AMPs) such as Aß. After this self-attack, the resulting necrotic (but not apoptotic) neuronal breakdown products diffuse to adjacent neurons eliciting further release of Aß, leading to a chronic self-perpetuating autoimmune cycle.  AD thus emerges as a brain-centric autoimmune disorder of innate immunity. Based upon the hypothesis that autoimmune processes are susceptible to endogenous regulatory processes, a subsequent comprehensive screening program of 1137 small molecules normally present in human brain identified tryptophan metabolism as a regulator of brain innate immunity and a source of potential endogenous anti-AD molecules capable of chemical modification into multi-site therapeutic modulators targeting AD's complex immunopathic-proteopathic pathogenesis. Discussion:  Conceptualizing AD as an autoimmune disease, identifying endogenous regulators of this autoimmunity, and designing small molecule drug-like analogues of these endogenous regulators represents a novel therapeutic approach for AD.

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.

Distribution of 54 polygenic risk scores for common diseases in long lived individuals and their offspring.

A surprising and well-replicated result in genetic studies of human longevity is that centenarians appear to carry disease-associated variants in numbers similar to the general population. With the proliferation of large genome-wide association studies (GWAS) in recent years, investigators have turned to polygenic scores to leverage GWAS results into a measure of genetic risk that can better predict the risk of disease than individual significant variants alone. We selected 54 polygenic risk scores (PRSs) developed for a variety of outcomes, and we calculated their values in individuals from the New England Centenarian Study (NECS, N = 4886) and the Long Life Family Study (LLFS, N = 4577). We compared the distribution of these PRSs among exceptionally long-lived individuals (ELLI), their offspring, and controls, and we also examined their predictive values, using t-tests and regression models adjusting for sex and principal components reflecting the ancestral background of the individuals (PCs). In our analyses, we controlled for multiple testing using a Bonferroni-adjusted threshold for 54 traits. We found that only 4 of the 54 PRSs differed between ELLIs and controls in both cohorts. ELLIs had significantly lower mean PRSs for Alzheimer's disease (AD) and coronary artery disease (CAD) than controls, suggesting a genetic predisposition to extreme longevity may be mediated by reduced susceptibility to these traits. ELLIs also had significantly higher mean PRSs for improved cognitive function and parental extreme longevity. In addition, the PRS for AD was associated with a higher risk of dementia among controls but not ELLIs (p = 0.003, 0.3 in NECS, p = 0.03, 0.9 in LLFS, respectively). ELLIs have a similar burden of genetic disease risk as the general population for most traits but have a significantly lower genetic risk of AD and CAD. The lack of association between AD PRS and dementia among ELLIs suggests that the genetic risk for AD that they do have is somehow counteracted by protective genetic or environmental factors.

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.

Using lipid profiling to better characterize metabolic differences in apolipoprotein E (APOE) genotype among community-dwelling older Black men.

Apolipoprotein E (APOE) allelic variation is associated with differences in overall circulating lipids and risks of major health outcomes. Lipid profiling provides the opportunity for a more detailed description of lipids that differ by APOE, to potentially inform therapeutic targets for mitigating higher morbidity and mortality associated with certain APOE genotypes. Here, we sought to identify lipids, lipid-like molecules, and important mediators of fatty acid metabolism that differ by APOE among 278 Black men ages 70-81. Using liquid chromatography-mass spectrometry methods, 222 plasma metabolites classified as lipids, lipid-like molecules, or essential in fatty acid metabolism were detected. We applied principal factor analyses to calculate a factor score for each main lipid category. APOE was categorized as ε4 carriers (n = 83; ε3ε4 or ε4ε4), ε2 carriers (n = 58; ε2ε3 or ε2ε2), or ε3 homozygotes (n = 137; ε3ε3). Using analysis of variance, the monoacylglycerol factor, cholesterol ester factor, the factor for triacylglycerols that consist mostly of polyunsaturated fatty acids, sphingosine, and free carnitine significantly differed by APOE (p < 0.05, false discovery rate < 0.30). The monoacylglycerol factor, cholesterol ester factor, and sphingosine were lower, whereas the factor for triacylglycerols that consisted mostly of polyunsaturated fatty acids was higher among ε2 carriers than remaining participants. Free carnitine was lower among ε4 carriers than ε3 homozygotes. Lower monoacylglycerols and cholesteryl esters and higher triacylglycerols that consist mostly of polyunsaturated fatty acids may be protective metabolic characteristics of APOE ε2 carriers, whereas lower carnitine may reflect altered mitochondrial functioning among ε4 carriers in this cohort of older Black men.

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.

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.

Relationship between socioeconomic status, exposure to airborne pollutants, and chronic rhinosinusitis disease severity.

BACKGROUND: Air pollution directly interacts with airway mucosa, yet little is known about how pollutants affect upper airway inflammation. Studies have shown increased incidence of chronic rhinosinusitis (CRS), rhinitis, and asthma in areas with higher traffic pollution, and these neighborhoods are often associated with lower socioeconomic status (SES). The Area Deprivation Index (ADI) assesses neighborhood-level SES by zip code. The purpose of this study was to assess the relationship between SES and exposure to inhaled pollutants and CRS disease severity. METHODS: CRS patients with and without nasal polyps (CRSwNP and CRSsNP, respectively) were identified (total patients = 234; CRSwNP patients = 138; CRSsNP patients = 96). Pollutant concentrations, including particulate matter 2.5 (PM2.5 ), black carbon (BC), and nitrogen dioxide (NO2 ), were measured at 70 sites within the defined countywide sites and used to estimate patient exposures. SES was measured by ADI state deciles. Disease severity metrics included the modified Lund-Mackay score (LMS), the need for systemic steroids, and functional endoscopic sinus surgery (FESS). Associations were analyzed and identified using linear, logistic, and Poisson multivariable regression. RESULTS: The distribution of CRSsNP and CRSwNP patients across ADI state deciles was similar. ADI, however, was a predictor of exposure to airborne pollutants (PM2.5 , BC, and NO2 ) with a 1.39%, 2.39%, and 2.49% increase in PM2.5 , BC, and NO2 per increasing decile increment (p < 0.0001), respectively, which demonstrated a direct correlation between deprived neighborhoods and higher levels of exposure to PM2.5 , BC, and NO2 with an increase in pollutant levels per increase in ADI decile. Furthermore, ADI was a predictor for increased steroid treatment. CONCLUSION: Lower SES predicted higher exposure to air pollution and increased disease severity in patients with CRS as demonstrated by the increased need for steroid treatment.

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.