Suchergebnisse

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Journals of Gerontology Series a-Biological Sciences and Medical Sciences following peer review. The definitive publisher-authenticated version Laddu, D., Parimi, N., Cauley, J. A., Cawthon, P. M., Ensrud, K. E., Orwoll, E., . . . Osteoporotic Fractures Men Mr, O. S. (2018). The Association Between Trajectories of Physical Activity and All-Cause and Cause-Specific Mortality. Journals of Gerontology Series a-Biological Sciences and Medical Sciences, 73(12), 1708-1713. doi:10.1093/gerona/gly037 is available online at: indigo.uic.edu. ; Background: The benefits of physical activity (PA) for health have primarily been evaluated during midlife. Whether patterns of change in late-life PA associate with overall and cause-specific mortality remains unclear. Methods: We examined the association between PA trajectories and subsequent mortality among 3,767 men aged ≥ 65 years. Men self-reported PA using the Physical Activity Scale for the Elderly scale (PASE) at up to 4 time points from 2000 through 2009 (Year 7); mortality was assessed over an average of 7.1 years after the Year 7 contact. Group-based trajectory modeling identified patterns of PA change. Cox proportional hazards models described associations between patterns of change in PA, Year 7 PA, and subsequent mortality risk. Results: Three discrete PA patterns were identified, all with declining PA. Compared to low-activity declining men, moderate (HR = 0.78; 95% CI: 0.70, 0.88) and high-activity (HR = 0.69, 95% CI: 0.57, 0.83) declining groups were associated with lower risk of all-cause mortality. Among models with a single time-point, the last time point (Year 7 PA score) was a strong predictor of mortality with HR = 0.85 (95% CI: 0.78, 0.93) per SD increase in PASE score. PA patterns were not a risk factor for mortality after adjustment for the Year 7 PA score. Conclusions: Recent PA levels are a stronger indicator of subsequent mortality risk than PA patterns reported over the prior 7 years or prior PA level, suggesting that current PA rather than history of PA is the most relevant parameter in clinical settings. ; The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Aging (NIA); the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); the National Center for Advancing Translational Sciences (NCATS); and NIH Roadmap for Medical Research (grant numbers U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128). This manuscript is the result of work supported with resources and use of facilities of the Minneapolis VA Health Care System. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.

Abstract

Background
This study quantifies incremental healthcare expenditures of functional impairments and phenotypic frailty in specific healthcare sectors.


Methods
Pooled 2023 analysis of 4 prospective cohort studies linked with Medicare claims including 4 318 women and 3 847 men attending an index examination (2002–2011). Annualized inpatient, skilled nursing facility (SNF), home healthcare (HHC), and outpatient costs (2023 dollars) ascertained for 36 months following index examination. Functional impairments (difficulty performing 4 activities of daily living) and frailty phenotype (operationalized using 5 components) derived from cohort data. Weighted multimorbidity index including demographics derived from claims.


Results
Mean age at index examination was 79.2 years. After accounting for multimorbidity and each other, average annualized incremental costs of 3–4 functional impairments versus no impairment in women (men) were $2 838 ($5 516) in inpatient, $1 572 ($1 446) in SNF, and $1 349 ($1 060) in HHC sectors; average incremental costs of phenotypic frailty versus robust in women (men) was $4 100 (not significant for men) in inpatient, $1 579 ($1 254) in SNF, and $645 ($526) in HHC sectors. Incremental inpatient costs were primarily due to a higher hospitalization risk, while incremental SNF and HHC costs were related to both increased risks of utilization and higher costs among individuals with utilization. Neither geriatric domain was associated with outpatient costs.


Conclusions
In this study of community-dwelling beneficiaries, functional impairments were independently associated with higher subsequent expenditures in inpatient, SNF, and HHC sectors among both sexes. Phenotypic frailty was independently associated with higher subsequent inpatient costs in women, and higher SNF and HHC costs in both sexes.

Abstract
Tryptophan (TRP) metabolites along the kynurenine (KYN) pathway (KP) have been found to influence muscle. Proinflammatory cytokines are known to stimulate the degradation of TRP down the KP. Given that both inflammation and KP metabolites have been connected with loss of muscle, we assessed the potential mediating role of KP metabolites on inflammation and muscle mass in older men. Five hundred and five men (85.0 ± 4.2 years) from the Osteoporotic Fractures in Men cohort study with measured D3-creatine dilution (D3Cr) muscle mass, KP metabolites, and inflammation markers (C-reactive protein [CRP], alpha-1-acid glycoprotein [AGP] and a subsample [n = 305] with interleukin [IL-6, IL-1β, IL-17A] and tumor necrosis factor-α [TNF-α]) were included in the analysis. KP metabolites and inflammatory markers were measured using liquid chromatography-tandem mass spectrometry and immunoassays, respectively. 23%–92% of the inverse relationship between inflammatory markers and D3Cr muscle mass was mediated by KP metabolites (indirect effect p < .05). 3-hydroxyanthranilic acid (3-HAA), quinolinic acid (QA), TRP, xanthurenic acid (XA), KYN/TRP, 3-hydroxykynurenine (3-HK)/3-HAA, QA/3-HAA, and nicotinamide (NAM)/QA mediated the AGP relationship. 3-HAA, QA, KYN/TRP, 3-HK/XA, HKr ratio, 3-HK/3-HAA, QA/3-HAA, and NAM/QA mediated the CRP. KYN/TRP, 3-HK/XA, and NAM/QA explained the relationship for IL-6 and 3-HK/XA and QA/3-HAA for TNF-α. No mediation effect was observed for the other cytokines (indirect effect p > .05). KP metabolites, particularly higher ratios of KYN/TRP, 3-HK/XA, 3-HK/3-HAA, QA/3-HAA, and a lower ratio of NAM/QA, mediated the relationship between inflammation and low muscle mass. Our preliminary cross-sectional data suggest that interventions to alter D3Cr muscle mass may focus on KP metabolites rather than inflammation per se.