Dataset Information

Plasma proteomic signature of the risk of developing mobility disability: A 9-year follow-up.

ABSTRACT: INTRODUCTION:Mobility disability is a powerful indicator of poor health in older adults. The biological and pathophysiological mechanism underlying the development of mobility disability remains unknown. This study conducted a data-driven discovery phase investigation to identify plasma proteins that predict the incidence of mobility disability in community-dwelling older adults without mobility disability at baseline. METHODS:We investigated 660 women and men, aged 71.9 ± 6.0 (60-94) years, who participated in the Invecchiare in Chianti, "Aging in the Chianti Area" study and completed the 400-m walk at fast pace (400-m walk) at enrollment. Median follow-up time was 8.57 [interquartile, 3.20-9.08] years. SOMAscan technology was used to measure 1,301 plasma proteins at enrollment. The incident of mobility disability was defined as inability to complete the 400-m walk. Protein-specific Cox proportional hazard model was adjusted for sex, age, and other important covariates. RESULTS:Plasma levels of 75 proteins predicted mobility disability (p < .05). Significant proteins were enriched for the KEGG "PI3K-Akt signaling," "phagosomes," and "cytokine-cytokine receptor interaction" pathways. After multiple comparison adjustment, plasma cathepsin S (CTSS; hazard ratio [HR] 1.33, 95% CI: 1.17, 1.51, q = 0.007), growth/differentiation factor 15 (GDF15; HR: 1.45, 95% CI: 1.23, 1.72, q = 0.007), and thrombospondin-2 (THBS2; HR: 1.44, 95% CI: 1.22, 1.69, q = 0.007) remained significantly associated with high risk of losing mobility. CONCLUSION:CTSS, GDF15, and THBS2 are novel blood biomarkers associated with new mobility disability in community-dwelling individuals. Overall, our analysis suggests that cellular senescence and inflammation should be targeted for prevention of mobility disability.

SUBMITTER: Osawa Y

PROVIDER: S-EPMC7189986 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Plasma proteomic signature of the risk of developing mobility disability: A 9-year follow-up.

Osawa Yusuke Y Semba Richard D RD Fantoni Giovanna G Candia Julián J Biancotto Angélique A Tanaka Toshiko T Bandinelli Stefania S Ferrucci Luigi L

Aging cell 20200310 4

<h4>Introduction</h4>Mobility disability is a powerful indicator of poor health in older adults. The biological and pathophysiological mechanism underlying the development of mobility disability remains unknown. This study conducted a data-driven discovery phase investigation to identify plasma proteins that predict the incidence of mobility disability in community-dwelling older adults without mobility disability at baseline.<h4>Methods</h4>We investigated 660 women and men, aged 71.9 ± 6.0 (60 ...[more]

PMID: 32157804

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Project description:ImportanceAlmost 1 in 4 women older than 65 years is unable to walk 2 to 3 blocks, and mobility disability is a key factor associated with loss of independence. Lack of moderate to vigorous-intensity physical activity is associated with mobility disability, but whether lighter physical activity is associated with mobility disability is unknown.ObjectiveTo determine the association of light-intensity physical activity and incident mobility disability among older women.Design, setting, and participantsThis prospective cohort study included women enrolled in the Objectively Measured Physical Activity and Cardiovascular Health study, an ancillary study of the Women's Health Initiative, between March 2012 and April 2014, with follow-up through March 31, 2018. The Women's Health Initiative was a population-based, multisite study that recruited from 40 clinical sites across the US. Participants in the present analysis included 5735 of 7058 ambulatory, community-dwelling women aged 63 years and older who returned an accelerometer with usable data, were free of mobility disability, and had follow-up data on mobility status. Data were analyzed from August 2018 to May 2019.ExposuresLight-intensity physical activity, defined as movement requiring energy expenditure between 1.6 and 2.9 metabolic equivalents, captured using an accelerometer over 7 days.Main outcomes and measuresIncident mobility disability, defined as the first self-reported inability to walk 1 block or up a flight of stairs at annual follow-up, and persistent incident mobility disability, defined as incident mobility loss that persisted through the end of follow-up.ResultsA total of 5735 participants were included for primary analysis of all incident mobility disability (mean [SD] age, 78.5 [6.6] years [range, 63-97 years]; 2811 [49.0%] White participants). Compared with women in the lowest quartile of light-intensity physical activity, lower risk of incident mobility disability was observed in quartile 2 (multivariable hazard ratio [HR], 0.78; 95% CI, 0.67-0.90), quartile 3 (HR, 0.60; 95% CI, 0.51-0.71), and quartile 4 (HR, 0.60; 95% CI, 0.51-0.71) (P < .001). This beneficial association was stronger for persistent mobility disability in quartile 2 (multivariable HR, 0.72; 95% CI, 0.60-0.85), quartile 3 (HR, 0.55; 95% CI, 0.46-0.67), and quartile 4 (HR, 0.52; 95% CI, 0.42-0.63) (P < .001). Stratified analyses showed the association was stronger among women with a body mass index of less than 30.0 (HR, 0.73; 95% CI, 0.66-0.82) compared with women with a body mass index of 30.0 or higher (HR, 0.91; 95% CI; 0.79-1.04; P = .04 for interaction).Conclusions and relevanceIn this cohort study, increased time spent in light-intensity physical activity was associated with reduced incident mobility disability. These findings support placing greater emphasis on promoting light-intensity physical activity for preserving mobility in later life.

Project description:Study designProspective cohort study.ObjectiveThe aim of this study was to identify treatment response trajectories in patients with low back pain (LBP) during and after multidisciplinary care in a tertiary spine center, and to examine baseline patient characteristics that can distinguish trajectories.Summary of background dataTreatment response is often heterogeneous between patients with LBP. Knowledge on key characteristics that are associated with courses of disability could identify patients at risk for less favorable outcome. This knowledge will help improve shared decision-making.MethodsAdult patients with LBP completed questionnaires on disability (Pain Disability Index) and LBP impact (Impact Stratification of the National Institutes of Health minimal dataset) at baseline, 6, 12, 18, and 24 months' follow-up. Latent class analyses were applied to identify trajectories of disability and LBP impact. Baseline sociodemographic and clinical patient characteristics were compared between trajectory subgroups.ResultsFollow-up was available for 996 patients on disability and 707 patients on LBP impact. Six trajectories were identified for both outcome measures. Three disability trajectories remained stable at distinct levels of severity (68% of patients) and three trajectories showed patterns of recovery (32%). For LBP impact there was one stable trajectory (17%), two slightly improving (59%), two recovering (15%), and one with a pattern of recovery and relapse (15%). Significant differences between trajectories were observed for almost all baseline patient characteristics.ConclusionOn average, patients show moderate improvements in disability and LBP impact 2 years after visiting a multidisciplinary tertiary spine center. However, latent class analyses revealed that most patients belong to subgroups experiencing stable levels of disability and LBP impact. Differences in baseline patient characteristics were mostly associated with baseline levels of functioning, instead of (un)favorable outcome during follow-up.Level of evidence2.

Dataset Information

Plasma proteomic signature of the risk of developing mobility disability: A 9-year follow-up.

Publications

Plasma proteomic signature of the risk of developing mobility disability: A 9-year follow-up.

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