Mid-life Epigenetic Age, Neuroimaging Brain Age, and Cognitive Function: Coronary Artery Risk Development in Young Adults (CARDIA) Study

Yinan Zheng; Mohamad Habes; Mitzi Gonzales; Raymond Pomponio; Ilya Nasrallah; Sadiya Khan; Douglas E. Vaughan; Christos Davatzikos; Sudha Seshadri; Lenore Launer; Farzaneh Sorond; Sanaz Sedaghat; Derek Wainwright; Andrea Baccarelli; Stephen Sidney; Nick Bryan; Philip Greenland; Donald Lloyd-Jones; Kristine Yaffe; Lifang Hou

doi:10.18632/aging.203918

Mid-life Epigenetic Age, Neuroimaging Brain Age, and Cognitive Function: Coronary Artery Risk Development in Young Adults (CARDIA) Study

Yinan Zheng^*, Mohamad Habes, Mitzi Gonzales, Raymond Pomponio, Ilya Nasrallah, Sadiya Khan, Douglas E. Vaughan, Christos Davatzikos, Sudha Seshadri, Lenore Launer, Farzaneh Sorond, Sanaz Sedaghat, Derek Wainwright, Andrea Baccarelli, Stephen Sidney, Nick Bryan, Philip Greenland, Donald Lloyd-Jones, Kristine Yaffe, Lifang Hou

^*Corresponding author for this work

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

22 Scopus citations

Abstract

The proportion of aging populations affected by dementia is increasing. There is an urgent need to identify biological aging markers in mid-life before symptoms of age-related dementia present for early intervention to delay the cognitive decline and the onset of dementia. In this cohort study involving 1,676 healthy participants (mean age 40) with up to 15 years of follow up, we evaluated the associations between cognitive function and two classes of novel biological aging markers: blood-based epigenetic aging and neuroimaging-based brain aging. Both accelerated epigenetic aging and brain aging were prospectively associated with worse cognitive outcomes. Specifically, every year faster epigenetic or brain aging was on average associated with 0.19-0.28 higher (worse) Stroop score, 0.04-0.05 lower (worse) RAVLT score, and 0.23-0.45 lower (worse) DSST (all false-discovery-rate-adjusted p <0.05). While epigenetic aging is a more stable biomarker with strong long-term predictive performance for cognitive function, brain aging biomarker may change more dynamically in temporal association with cognitive decline. The combined model using epigenetic and brain aging markers achieved the highest accuracy (AUC: 0.68, p<0.001) in predicting global cognitive function status. Accelerated epigenetic age and brain age at midlife may aid timely identification of individuals at risk for accelerated cognitive decline and promote the development of interventions to preserve optimal functioning across the lifespan.

Original language	English (US)
Pages (from-to)	1691-1712
Number of pages	22
Journal	Aging
Volume	14
Issue number	4
DOIs	https://doi.org/10.18632/aging.203918
State	Published - 2022

Funding

The study was funded by NIH/NIA grant R01AG069120. The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201800005I and HHSN2682018 00007I), Northwestern University (HHSN2682018000 03I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN 268201800004I). CARDIA was also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between NIA and NHLBI (AG0005). The DNA methylation laboratory work and analytical component were funded by American Heart Association (17SFRN33700278 and 14SFRN20790000, Northwestern University, PI: Dr. Lifang Hou). This manuscript has been reviewed by CARDIA for scientific content.

Keywords

Brain age
Cognitive function
Dna methylation
Epigenetic age
Magnetic resonance imaging

ASJC Scopus subject areas

Aging
Cell Biology

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10.18632/aging.203918

Cite this

Zheng, Y., Habes, M., Gonzales, M., Pomponio, R., Nasrallah, I., Khan, S., Vaughan, D. E., Davatzikos, C., Seshadri, S., Launer, L., Sorond, F., Sedaghat, S., Wainwright, D., Baccarelli, A., Sidney, S., Bryan, N., Greenland, P., Lloyd-Jones, D., Yaffe, K., & Hou, L. (2022). Mid-life Epigenetic Age, Neuroimaging Brain Age, and Cognitive Function: Coronary Artery Risk Development in Young Adults (CARDIA) Study. Aging, 14(4), 1691-1712. https://doi.org/10.18632/aging.203918

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title = "Mid-life Epigenetic Age, Neuroimaging Brain Age, and Cognitive Function: Coronary Artery Risk Development in Young Adults (CARDIA) Study",

abstract = "The proportion of aging populations affected by dementia is increasing. There is an urgent need to identify biological aging markers in mid-life before symptoms of age-related dementia present for early intervention to delay the cognitive decline and the onset of dementia. In this cohort study involving 1,676 healthy participants (mean age 40) with up to 15 years of follow up, we evaluated the associations between cognitive function and two classes of novel biological aging markers: blood-based epigenetic aging and neuroimaging-based brain aging. Both accelerated epigenetic aging and brain aging were prospectively associated with worse cognitive outcomes. Specifically, every year faster epigenetic or brain aging was on average associated with 0.19-0.28 higher (worse) Stroop score, 0.04-0.05 lower (worse) RAVLT score, and 0.23-0.45 lower (worse) DSST (all false-discovery-rate-adjusted p <0.05). While epigenetic aging is a more stable biomarker with strong long-term predictive performance for cognitive function, brain aging biomarker may change more dynamically in temporal association with cognitive decline. The combined model using epigenetic and brain aging markers achieved the highest accuracy (AUC: 0.68, p<0.001) in predicting global cognitive function status. Accelerated epigenetic age and brain age at midlife may aid timely identification of individuals at risk for accelerated cognitive decline and promote the development of interventions to preserve optimal functioning across the lifespan.",

keywords = "Brain age, Cognitive function, Dna methylation, Epigenetic age, Magnetic resonance imaging",

author = "Yinan Zheng and Mohamad Habes and Mitzi Gonzales and Raymond Pomponio and Ilya Nasrallah and Sadiya Khan and Vaughan, {Douglas E.} and Christos Davatzikos and Sudha Seshadri and Lenore Launer and Farzaneh Sorond and Sanaz Sedaghat and Derek Wainwright and Andrea Baccarelli and Stephen Sidney and Nick Bryan and Philip Greenland and Donald Lloyd-Jones and Kristine Yaffe and Lifang Hou",

note = "Funding Information: The study was funded by NIH/NIA grant R01AG069120. The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201800005I and HHSN2682018 00007I), Northwestern University (HHSN2682018000 03I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN 268201800004I). CARDIA was also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between NIA and NHLBI (AG0005). The DNA methylation laboratory work and analytical component were funded by American Heart Association (17SFRN33700278 and 14SFRN20790000, Northwestern University, PI: Dr. Lifang Hou). This manuscript has been reviewed by CARDIA for scientific content. Publisher Copyright: {\textcopyright} 2022 Zheng et al.",

year = "2022",

doi = "10.18632/aging.203918",

language = "English (US)",

volume = "14",

pages = "1691--1712",

journal = "Aging",

issn = "1945-4589",

publisher = "Impact Journals LLC",

number = "4",

}

Zheng, Y, Habes, M, Gonzales, M, Pomponio, R, Nasrallah, I, Khan, S , Vaughan, DE, Davatzikos, C, Seshadri, S, Launer, L, Sorond, F, Sedaghat, S, Wainwright, D, Baccarelli, A, Sidney, S, Bryan, N, Greenland, P, Lloyd-Jones, D, Yaffe, K & Hou, L 2022, 'Mid-life Epigenetic Age, Neuroimaging Brain Age, and Cognitive Function: Coronary Artery Risk Development in Young Adults (CARDIA) Study', Aging, vol. 14, no. 4, pp. 1691-1712. https://doi.org/10.18632/aging.203918

TY - JOUR

T1 - Mid-life Epigenetic Age, Neuroimaging Brain Age, and Cognitive Function

T2 - Coronary Artery Risk Development in Young Adults (CARDIA) Study

AU - Zheng, Yinan

AU - Habes, Mohamad

AU - Gonzales, Mitzi

AU - Pomponio, Raymond

AU - Nasrallah, Ilya

AU - Khan, Sadiya

AU - Vaughan, Douglas E.

AU - Davatzikos, Christos

AU - Seshadri, Sudha

AU - Launer, Lenore

AU - Sorond, Farzaneh

AU - Sedaghat, Sanaz

AU - Wainwright, Derek

AU - Baccarelli, Andrea

AU - Sidney, Stephen

AU - Bryan, Nick

AU - Greenland, Philip

AU - Lloyd-Jones, Donald

AU - Yaffe, Kristine

AU - Hou, Lifang

N1 - Funding Information: The study was funded by NIH/NIA grant R01AG069120. The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201800005I and HHSN2682018 00007I), Northwestern University (HHSN2682018000 03I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN 268201800004I). CARDIA was also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between NIA and NHLBI (AG0005). The DNA methylation laboratory work and analytical component were funded by American Heart Association (17SFRN33700278 and 14SFRN20790000, Northwestern University, PI: Dr. Lifang Hou). This manuscript has been reviewed by CARDIA for scientific content. Publisher Copyright: © 2022 Zheng et al.

PY - 2022

Y1 - 2022

N2 - The proportion of aging populations affected by dementia is increasing. There is an urgent need to identify biological aging markers in mid-life before symptoms of age-related dementia present for early intervention to delay the cognitive decline and the onset of dementia. In this cohort study involving 1,676 healthy participants (mean age 40) with up to 15 years of follow up, we evaluated the associations between cognitive function and two classes of novel biological aging markers: blood-based epigenetic aging and neuroimaging-based brain aging. Both accelerated epigenetic aging and brain aging were prospectively associated with worse cognitive outcomes. Specifically, every year faster epigenetic or brain aging was on average associated with 0.19-0.28 higher (worse) Stroop score, 0.04-0.05 lower (worse) RAVLT score, and 0.23-0.45 lower (worse) DSST (all false-discovery-rate-adjusted p <0.05). While epigenetic aging is a more stable biomarker with strong long-term predictive performance for cognitive function, brain aging biomarker may change more dynamically in temporal association with cognitive decline. The combined model using epigenetic and brain aging markers achieved the highest accuracy (AUC: 0.68, p<0.001) in predicting global cognitive function status. Accelerated epigenetic age and brain age at midlife may aid timely identification of individuals at risk for accelerated cognitive decline and promote the development of interventions to preserve optimal functioning across the lifespan.

AB - The proportion of aging populations affected by dementia is increasing. There is an urgent need to identify biological aging markers in mid-life before symptoms of age-related dementia present for early intervention to delay the cognitive decline and the onset of dementia. In this cohort study involving 1,676 healthy participants (mean age 40) with up to 15 years of follow up, we evaluated the associations between cognitive function and two classes of novel biological aging markers: blood-based epigenetic aging and neuroimaging-based brain aging. Both accelerated epigenetic aging and brain aging were prospectively associated with worse cognitive outcomes. Specifically, every year faster epigenetic or brain aging was on average associated with 0.19-0.28 higher (worse) Stroop score, 0.04-0.05 lower (worse) RAVLT score, and 0.23-0.45 lower (worse) DSST (all false-discovery-rate-adjusted p <0.05). While epigenetic aging is a more stable biomarker with strong long-term predictive performance for cognitive function, brain aging biomarker may change more dynamically in temporal association with cognitive decline. The combined model using epigenetic and brain aging markers achieved the highest accuracy (AUC: 0.68, p<0.001) in predicting global cognitive function status. Accelerated epigenetic age and brain age at midlife may aid timely identification of individuals at risk for accelerated cognitive decline and promote the development of interventions to preserve optimal functioning across the lifespan.

KW - Brain age

KW - Cognitive function

KW - Dna methylation

KW - Epigenetic age

KW - Magnetic resonance imaging

UR - http://www.scopus.com/inward/record.url?scp=85125712809&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85125712809&partnerID=8YFLogxK

U2 - 10.18632/aging.203918

DO - 10.18632/aging.203918

M3 - Article

C2 - 35220276

AN - SCOPUS:85125712809

SN - 1945-4589

VL - 14

SP - 1691

EP - 1712

JO - Aging

JF - Aging

IS - 4

ER -

Mid-life Epigenetic Age, Neuroimaging Brain Age, and Cognitive Function: Coronary Artery Risk Development in Young Adults (CARDIA) Study

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