Prediction of disability-free survival in healthy older people

the ASPREE investigators

doi:10.1007/s11357-022-00547-x

Prediction of disability-free survival in healthy older people

the ASPREE investigators

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6–77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people. Trial registration Clinicaltrials.gov (NCT01038583).

Original language	English (US)
Pages (from-to)	1641-1655
Number of pages	15
Journal	GeroScience
Volume	44
Issue number	3
DOIs	https://doi.org/10.1007/s11357-022-00547-x
State	Published - Jun 1 2022

Bibliographical note

Funding Information:
We thank the ASPREE trial staff, participants and general practitioners. ASPREE investigators and committees International Steering Committee: John McNeil (Chair and Principal Investigator), Anne Murray (Co-Chair and Co-Principal Investigator), Lawrie Beilin, Andrew Chan, Jamehl Demons, Michael Ernst, Sara Espinoza, Matthew Goetz, Colin Johnston, Brenda Kirpach, Danny Liew, Karen Margolis, Frank Meyskens, Mark Nelson, Chris Reid, Raj Shah, Elsdon Storey, Andrew Tonkin, Rory Wolfe, Robyn Woods, John Zalcberg International End Point Adjudication Committees: Mark Nelson (Chair), Diane Ives (Co-Chair), Michael Berk, Wendy Bernstein, Donna Brauer, Christine Burns, Trevor Chong, Geoff Cloud, Jamehl Demons, Geoffrey Donnan, Charles Eaton, Paul Fitzgerald, Peter Gibbs, Andrew Haydon, Michael Jelinek, Finlay Macrae, Suzanne Mahady, Mobin Malik, Karen Margolis, Catriona McLean, Anne Murray, Anne Newman, Luz Rodriguez, Suzanne Satterfield (deceased), Raj Shah, Elsdon Storey, Jeanne Tie, Andrew Tonkin, Gijsberta van Londen, Stephanie Ward, Jeff Williamson, Erica Wood, John Zalcberg Data and Safety Monitoring Board: Jay Mohr (Chair).

Funding Information:
Open Access funding enabled and organized by CAUL and its Member Institutions This study was financially supported by the National Institute on Aging and the National Cancer Institute at the National Institutes of Health (grant numbers U01AG029824, U19AG062682); the National Health and Medical Research Council of Australia (grant numbers 334047, 1127060); Monash University; and the Victorian Cancer Agency. J.N. is recipient of a fellowship by the Deutsche Forschungsgemeinschaft (NE 2165/1-1). C.M.R. is supported through a NHMRC Principal Research Fellowship (APP 1136372). JMCN is supported through an NHMRC Leadership Fellowship (IG 1173690).

Publisher Copyright:
© 2022, The Author(s).

Keywords

Disability
Elderly
Healthy
Public Health
Risk prediction
Survival

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s11357-022-00547-x

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@article{5102a5b31266403fb9638ee6e39af9ec,

title = "Prediction of disability-free survival in healthy older people",

abstract = "Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6–77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people. Trial registration Clinicaltrials.gov (NCT01038583).",

keywords = "Disability, Elderly, Healthy, Public Health, Risk prediction, Survival",

author = "{the ASPREE investigators} and Neumann, {Johannes Tobias} and Thao, {Le T.P.} and Murray, {Anne M.} and Emily Callander and Carr, {Prudence R.} and Nelson, {Mark R.} and Rory Wolfe and Woods, {Robyn L.} and Reid, {Christopher M.} and Shah, {Raj C.} and Newman, {Anne B.} and Williamson, {Jeff D.} and Tonkin, {Andrew M.} and McNeil, {John J.} and Anne Murray and Lawrie Beilin and Andrew Chan and Jamehl Demons and Michael Ernst and Sara Espinoza and Matthew Goetz and Colin Johnston and Brenda Kirpach and Danny Liew and Karen Margolis and Frank Meyskens and Chris Reid and Raj Shah and Elsdon Storey and Robyn Woods and John Zalcberg and Diane Ives and Michael Berk and Wendy Bernstein and Donna Brauer and Christine Burns and Trevor Chong and Geoff Cloud and Jamehl Demons and Donnan, {Geoffrey A.} and Charles Eaton and Margolis, {Karen L} and Margolis, {Karen L} and Dave Gilbertson and Margolis, {Karen L} and Kevin Peterson and P. Duane and S. Frost and Murray, {Anne M} and N. Sandhu",

note = "Funding Information: We thank the ASPREE trial staff, participants and general practitioners. ASPREE investigators and committees International Steering Committee: John McNeil (Chair and Principal Investigator), Anne Murray (Co-Chair and Co-Principal Investigator), Lawrie Beilin, Andrew Chan, Jamehl Demons, Michael Ernst, Sara Espinoza, Matthew Goetz, Colin Johnston, Brenda Kirpach, Danny Liew, Karen Margolis, Frank Meyskens, Mark Nelson, Chris Reid, Raj Shah, Elsdon Storey, Andrew Tonkin, Rory Wolfe, Robyn Woods, John Zalcberg International End Point Adjudication Committees: Mark Nelson (Chair), Diane Ives (Co-Chair), Michael Berk, Wendy Bernstein, Donna Brauer, Christine Burns, Trevor Chong, Geoff Cloud, Jamehl Demons, Geoffrey Donnan, Charles Eaton, Paul Fitzgerald, Peter Gibbs, Andrew Haydon, Michael Jelinek, Finlay Macrae, Suzanne Mahady, Mobin Malik, Karen Margolis, Catriona McLean, Anne Murray, Anne Newman, Luz Rodriguez, Suzanne Satterfield (deceased), Raj Shah, Elsdon Storey, Jeanne Tie, Andrew Tonkin, Gijsberta van Londen, Stephanie Ward, Jeff Williamson, Erica Wood, John Zalcberg Data and Safety Monitoring Board: Jay Mohr (Chair). Funding Information: Open Access funding enabled and organized by CAUL and its Member Institutions This study was financially supported by the National Institute on Aging and the National Cancer Institute at the National Institutes of Health (grant numbers U01AG029824, U19AG062682); the National Health and Medical Research Council of Australia (grant numbers 334047, 1127060); Monash University; and the Victorian Cancer Agency. J.N. is recipient of a fellowship by the Deutsche Forschungsgemeinschaft (NE 2165/1-1). C.M.R. is supported through a NHMRC Principal Research Fellowship (APP 1136372). JMCN is supported through an NHMRC Leadership Fellowship (IG 1173690). Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = jun,

day = "1",

doi = "10.1007/s11357-022-00547-x",

language = "English (US)",

volume = "44",

pages = "1641--1655",

journal = "GeroScience",

issn = "2509-2715",

publisher = "Springer International Publishing AG",

number = "3",

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TY - JOUR

T1 - Prediction of disability-free survival in healthy older people

AU - the ASPREE investigators

AU - Neumann, Johannes Tobias

AU - Thao, Le T.P.

AU - Murray, Anne M.

AU - Callander, Emily

AU - Carr, Prudence R.

AU - Nelson, Mark R.

AU - Wolfe, Rory

AU - Woods, Robyn L.

AU - Reid, Christopher M.

AU - Shah, Raj C.

AU - Newman, Anne B.

AU - Williamson, Jeff D.

AU - Tonkin, Andrew M.

AU - McNeil, John J.

AU - Murray, Anne

AU - Beilin, Lawrie

AU - Chan, Andrew

AU - Demons, Jamehl

AU - Ernst, Michael

AU - Espinoza, Sara

AU - Goetz, Matthew

AU - Johnston, Colin

AU - Kirpach, Brenda

AU - Liew, Danny

AU - Margolis, Karen

AU - Meyskens, Frank

AU - Reid, Chris

AU - Shah, Raj

AU - Storey, Elsdon

AU - Woods, Robyn

AU - Zalcberg, John

AU - Ives, Diane

AU - Berk, Michael

AU - Bernstein, Wendy

AU - Brauer, Donna

AU - Burns, Christine

AU - Chong, Trevor

AU - Cloud, Geoff

AU - Demons, Jamehl

AU - Donnan, Geoffrey A.

AU - Eaton, Charles

AU - Margolis, Karen L

AU - Gilbertson, Dave

AU - Margolis, Karen L

AU - Peterson, Kevin

AU - Duane, P.

AU - Frost, S.

AU - Murray, Anne M

AU - Sandhu, N.

N1 - Funding Information: We thank the ASPREE trial staff, participants and general practitioners. ASPREE investigators and committees International Steering Committee: John McNeil (Chair and Principal Investigator), Anne Murray (Co-Chair and Co-Principal Investigator), Lawrie Beilin, Andrew Chan, Jamehl Demons, Michael Ernst, Sara Espinoza, Matthew Goetz, Colin Johnston, Brenda Kirpach, Danny Liew, Karen Margolis, Frank Meyskens, Mark Nelson, Chris Reid, Raj Shah, Elsdon Storey, Andrew Tonkin, Rory Wolfe, Robyn Woods, John Zalcberg International End Point Adjudication Committees: Mark Nelson (Chair), Diane Ives (Co-Chair), Michael Berk, Wendy Bernstein, Donna Brauer, Christine Burns, Trevor Chong, Geoff Cloud, Jamehl Demons, Geoffrey Donnan, Charles Eaton, Paul Fitzgerald, Peter Gibbs, Andrew Haydon, Michael Jelinek, Finlay Macrae, Suzanne Mahady, Mobin Malik, Karen Margolis, Catriona McLean, Anne Murray, Anne Newman, Luz Rodriguez, Suzanne Satterfield (deceased), Raj Shah, Elsdon Storey, Jeanne Tie, Andrew Tonkin, Gijsberta van Londen, Stephanie Ward, Jeff Williamson, Erica Wood, John Zalcberg Data and Safety Monitoring Board: Jay Mohr (Chair). Funding Information: Open Access funding enabled and organized by CAUL and its Member Institutions This study was financially supported by the National Institute on Aging and the National Cancer Institute at the National Institutes of Health (grant numbers U01AG029824, U19AG062682); the National Health and Medical Research Council of Australia (grant numbers 334047, 1127060); Monash University; and the Victorian Cancer Agency. J.N. is recipient of a fellowship by the Deutsche Forschungsgemeinschaft (NE 2165/1-1). C.M.R. is supported through a NHMRC Principal Research Fellowship (APP 1136372). JMCN is supported through an NHMRC Leadership Fellowship (IG 1173690). Publisher Copyright: © 2022, The Author(s).

PY - 2022/6/1

Y1 - 2022/6/1

N2 - Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6–77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people. Trial registration Clinicaltrials.gov (NCT01038583).

AB - Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6–77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people. Trial registration Clinicaltrials.gov (NCT01038583).

KW - Disability

KW - Elderly

KW - Healthy

KW - Public Health

KW - Risk prediction

KW - Survival

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UR - http://www.scopus.com/inward/citedby.url?scp=85132455784&partnerID=8YFLogxK

U2 - 10.1007/s11357-022-00547-x

DO - 10.1007/s11357-022-00547-x

M3 - Article

C2 - 35420334

AN - SCOPUS:85132455784

SN - 2509-2715

VL - 44

SP - 1641

EP - 1655

JO - GeroScience

JF - GeroScience

IS - 3

ER -

Prediction of disability-free survival in healthy older people

Abstract

Bibliographical note

Keywords

UN SDGs

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