Mid-life Epigenetic Age, Brain Age and Cognitive Function in the CARDIA Cohort

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March 2, 2022

Aging (Aging-US) published this trending research paper as the cover for Volume 14, Issue 4 on February 27, 2022, entitled, “Mid-life epigenetic age, neuroimaging brain age, and cognitive function: coronary artery risk development in young adults (CARDIA) study” by researchers from the Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL; Biggs Institute Neuroimaging Core, Glenn Biggs Institute for Neurodegenerative Disorders, University of Texas Health Science Center at San Antonio, San Antonio, TX; Department of Radiology, University of Pennsylvania, Philadelphia, PA; Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL; Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL; Department of Neurology, Boston University School of Medicine, Boston, MA; Laboratory of Epidemiology and Population Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN; Departments of Neurological Surgery, Medicine-Hematology and Oncology, Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL; Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY; Kaiser Permanente Division of Research, Oakland, CA; Department of Diagnostic Medicine, Dell Medical School, University of Texas at Austin, Austin, TX; Departments of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA; Department of Neurology University of California, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California San Francisco, CA; San Francisco VA Medical Center, San Francisco, CA. DOI - https://doi.org/10.18632/aging.203918 Corresponding Authors - Yinan Zheng - y-zheng@northwestern.edu, Kristine Yaffe - Kristine.Yaffe@ucsf.edu, and Lifang Hou - l-hou@northwestern.edu 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 - cognitive function, epigenetic age, brain age, DNA methylation, magnetic resonance imaging About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at http://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Aging-US is published by Impact Journals, LLC: http://www.ImpactJournals.com​​ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

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