Development and Validation of Models to Estimate the Incident Risk of Cognitive Impairment and Atherosclerotic Cardiovascular Disease in Older Adults

Background Guidelines emphasize using atherosclerotic cardiovascular disease (ASCVD) risk prediction models for treatment decisions, but risk of cognitive impairment is an equally important concern in older adults. Current ASCVD risk prediction models were derived in younger adults and do not includ...

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Main Authors: Michael G. Nanna, Daniel Wojdyla, Eric D. Peterson, Ann Marie Navar, Jeff D. Williamson, Lisandro D. Colantonio, Stephen Y. Wang, Yasser Jamil, Alain G. Bertoni, Musarrat Nahid, Abdulla A. Damluji, Parag Goyal, Sarwat I. Chaudhry, Thomas M. Gill, Karen P. Alexander
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.038949
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author Michael G. Nanna
Daniel Wojdyla
Eric D. Peterson
Ann Marie Navar
Jeff D. Williamson
Lisandro D. Colantonio
Stephen Y. Wang
Yasser Jamil
Alain G. Bertoni
Musarrat Nahid
Abdulla A. Damluji
Parag Goyal
Sarwat I. Chaudhry
Thomas M. Gill
Karen P. Alexander
author_facet Michael G. Nanna
Daniel Wojdyla
Eric D. Peterson
Ann Marie Navar
Jeff D. Williamson
Lisandro D. Colantonio
Stephen Y. Wang
Yasser Jamil
Alain G. Bertoni
Musarrat Nahid
Abdulla A. Damluji
Parag Goyal
Sarwat I. Chaudhry
Thomas M. Gill
Karen P. Alexander
author_sort Michael G. Nanna
collection DOAJ
description Background Guidelines emphasize using atherosclerotic cardiovascular disease (ASCVD) risk prediction models for treatment decisions, but risk of cognitive impairment is an equally important concern in older adults. Current ASCVD risk prediction models were derived in younger adults and do not include holistic measures of health or predict cognitive impairment. Methods We utilized data from the Framingham, Framingham Offspring, CHS (Cardiovascular Health Study), and ARIC (Atherosclerosis Risk in Communities) cohorts to derive and validate 2 Selective Functional Prediction models to estimate an older person's (aged ≥75 years) risk within 5 years of developing incident: (1) cognitive impairment; and (2) ASCVD, while accounting for the competing risk of death. Variable selection, including functional status, was based on the least absolute shrinkage and selection operator method. The cognitive impairment (N=3466) and ASCVD (N=4403) model populations were split into derivation and validation cohorts with external validation, then performed in MESA (Multi‐Ethnic Study of Atherosclerosis). Results In the derivation and external validation cohorts (median age, 79 years), 579 (16.7%) and 67 (15.3%) participants developed incident cognitive impairment, respectively; 748 (17.0%) and 80 (8.4%), respectively, experienced an ASCVD event. The cognitive impairment model (baseline Mini‐Mental State Examination (MMSE), atrial fibrillation, antidepressant use, mobility impairment, and dependence for grocery shopping) had good discrimination in the internal and external validation cohorts (C index 0.75 and 0.73, respectively). The ASCVD model (employment status, MMSE, aspirin, lipid‐lowering medications, blood pressure medications, systolic blood pressure, general health status, high‐density lipoprotein cholesterol, triglycerides, creatinine, and mobility impairment) had satisfactory discrimination (C index 0.67) on internal validation and outperformed the pooled cohort equations, but had modest discrimination (C index 0.59) on external validation. Although both models were well calibrated in the internal validation cohorts, they overpredicted risk in the external validation cohort. Conclusions Accurate prediction of an older person's risk of developing cognitive impairment is possible, but predicting future ASCVD events remains more challenging.
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spelling doaj-art-e1896cb26d57463d9407c39bdaad7cbe2025-08-20T03:31:07ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-06-01141110.1161/JAHA.124.038949Development and Validation of Models to Estimate the Incident Risk of Cognitive Impairment and Atherosclerotic Cardiovascular Disease in Older AdultsMichael G. Nanna0Daniel Wojdyla1Eric D. Peterson2Ann Marie Navar3Jeff D. Williamson4Lisandro D. Colantonio5Stephen Y. Wang6Yasser Jamil7Alain G. Bertoni8Musarrat Nahid9Abdulla A. Damluji10Parag Goyal11Sarwat I. Chaudhry12Thomas M. Gill13Karen P. Alexander14Section of Cardiovascular Medicine, Yale School of Medicine New Haven CT USADuke Clinical Research Institute Durham NC USADivision of Cardiology UT Southwestern Medical Center Dallas TX USADivision of Cardiology UT Southwestern Medical Center Dallas TX USASection on Gerontology and Geriatric Medicine and the Sticht Center for Healthy Aging and Alzheimer’s Prevention at Wake Forest School of Medicine Winston‐Salem NC USADepartment of Epidemiology, School of Public Health University of Alabama at Birmingham Birmingham AL USADivision of Cardiology The CardioVascular Center, Tufts Medical Center Boston MA USASection of Cardiovascular Medicine Department of Internal Medicine, Inova Schar Heart and Vascular Institute Falls Church VA USASection of Epidemiology and Prevention, Wake Forest School of Medicine Winston‐Salem NC USADivision of General Internal Medicine, Weill Cornell Medicine New York NY USAInova Center of Outcomes Research Falls Church VA USAProgram for the Care and Study of the Aging Heart, Department of Medicine, Weill Cornell Medicine New York NY USADepartment of Internal Medicine, Yale School of Medicine New Haven CT USADivision of Geriatrics Yale School of Medicine New Haven CT USADuke Clinical Research Institute Durham NC USABackground Guidelines emphasize using atherosclerotic cardiovascular disease (ASCVD) risk prediction models for treatment decisions, but risk of cognitive impairment is an equally important concern in older adults. Current ASCVD risk prediction models were derived in younger adults and do not include holistic measures of health or predict cognitive impairment. Methods We utilized data from the Framingham, Framingham Offspring, CHS (Cardiovascular Health Study), and ARIC (Atherosclerosis Risk in Communities) cohorts to derive and validate 2 Selective Functional Prediction models to estimate an older person's (aged ≥75 years) risk within 5 years of developing incident: (1) cognitive impairment; and (2) ASCVD, while accounting for the competing risk of death. Variable selection, including functional status, was based on the least absolute shrinkage and selection operator method. The cognitive impairment (N=3466) and ASCVD (N=4403) model populations were split into derivation and validation cohorts with external validation, then performed in MESA (Multi‐Ethnic Study of Atherosclerosis). Results In the derivation and external validation cohorts (median age, 79 years), 579 (16.7%) and 67 (15.3%) participants developed incident cognitive impairment, respectively; 748 (17.0%) and 80 (8.4%), respectively, experienced an ASCVD event. The cognitive impairment model (baseline Mini‐Mental State Examination (MMSE), atrial fibrillation, antidepressant use, mobility impairment, and dependence for grocery shopping) had good discrimination in the internal and external validation cohorts (C index 0.75 and 0.73, respectively). The ASCVD model (employment status, MMSE, aspirin, lipid‐lowering medications, blood pressure medications, systolic blood pressure, general health status, high‐density lipoprotein cholesterol, triglycerides, creatinine, and mobility impairment) had satisfactory discrimination (C index 0.67) on internal validation and outperformed the pooled cohort equations, but had modest discrimination (C index 0.59) on external validation. Although both models were well calibrated in the internal validation cohorts, they overpredicted risk in the external validation cohort. Conclusions Accurate prediction of an older person's risk of developing cognitive impairment is possible, but predicting future ASCVD events remains more challenging.https://www.ahajournals.org/doi/10.1161/JAHA.124.038949cardiovascular diseasecognitive impairmentgeriatricolder adultspreventionrisk prediction
spellingShingle Michael G. Nanna
Daniel Wojdyla
Eric D. Peterson
Ann Marie Navar
Jeff D. Williamson
Lisandro D. Colantonio
Stephen Y. Wang
Yasser Jamil
Alain G. Bertoni
Musarrat Nahid
Abdulla A. Damluji
Parag Goyal
Sarwat I. Chaudhry
Thomas M. Gill
Karen P. Alexander
Development and Validation of Models to Estimate the Incident Risk of Cognitive Impairment and Atherosclerotic Cardiovascular Disease in Older Adults
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
cardiovascular disease
cognitive impairment
geriatric
older adults
prevention
risk prediction
title Development and Validation of Models to Estimate the Incident Risk of Cognitive Impairment and Atherosclerotic Cardiovascular Disease in Older Adults
title_full Development and Validation of Models to Estimate the Incident Risk of Cognitive Impairment and Atherosclerotic Cardiovascular Disease in Older Adults
title_fullStr Development and Validation of Models to Estimate the Incident Risk of Cognitive Impairment and Atherosclerotic Cardiovascular Disease in Older Adults
title_full_unstemmed Development and Validation of Models to Estimate the Incident Risk of Cognitive Impairment and Atherosclerotic Cardiovascular Disease in Older Adults
title_short Development and Validation of Models to Estimate the Incident Risk of Cognitive Impairment and Atherosclerotic Cardiovascular Disease in Older Adults
title_sort development and validation of models to estimate the incident risk of cognitive impairment and atherosclerotic cardiovascular disease in older adults
topic cardiovascular disease
cognitive impairment
geriatric
older adults
prevention
risk prediction
url https://www.ahajournals.org/doi/10.1161/JAHA.124.038949
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