Association of a pace of aging epigenetic clock with rate of cognitive decline in the Framingham Heart Study Offspring Cohort

Abstract INTRODUCTION The geroscience hypothesis proposes systemic biological aging is a root cause of cognitive decline. METHODS We analyzed Framingham Heart Study Offspring Cohort data (n = 2296; 46% male; baseline age M = 62, SD = 9, range = 25–101 y). We measured cognitive decline across two dec...

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Main Authors: Micah J. Savin, Haoyang Wang, Heming Pei, Allison E. Aiello, Stephanie Assuras, Avshalom Caspi, Terrie E. Moffitt, Peter A. Muenning, Calen P. Ryan, Baoyi Shi, Yaakov Stern, Karen Sugden, Linda Valeri, Daniel W. Belsky
Format: Article
Language:English
Published: Wiley 2024-10-01
Series:Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring
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Online Access:https://doi.org/10.1002/dad2.70038
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author Micah J. Savin
Haoyang Wang
Heming Pei
Allison E. Aiello
Stephanie Assuras
Avshalom Caspi
Terrie E. Moffitt
Peter A. Muenning
Calen P. Ryan
Baoyi Shi
Yaakov Stern
Karen Sugden
Linda Valeri
Daniel W. Belsky
author_facet Micah J. Savin
Haoyang Wang
Heming Pei
Allison E. Aiello
Stephanie Assuras
Avshalom Caspi
Terrie E. Moffitt
Peter A. Muenning
Calen P. Ryan
Baoyi Shi
Yaakov Stern
Karen Sugden
Linda Valeri
Daniel W. Belsky
author_sort Micah J. Savin
collection DOAJ
description Abstract INTRODUCTION The geroscience hypothesis proposes systemic biological aging is a root cause of cognitive decline. METHODS We analyzed Framingham Heart Study Offspring Cohort data (n = 2296; 46% male; baseline age M = 62, SD = 9, range = 25–101 y). We measured cognitive decline across two decades of neuropsychological‐testing follow‐up. We measured pace of aging using the DunedinPACE epigenetic clock. Analysis tested if participants with faster DunedinPACE values experienced more rapid cognitive decline compared with those with slower DunedinPACE values. RESULTS Participants with faster DunedinPACE had poorer cognitive functioning at baseline and experienced more rapid cognitive decline over follow‐up. Results were robust to confounders and consistent across population strata. Findings were similar for the PhenoAge and GrimAge epigenetic clocks. DISCUSSION Faster pace of aging is a risk factor for preclinical cognitive decline. Metrics of biological aging may inform risk stratification in clinical trials and prognosis in patient care. Highlights Faster DunedinPACE is associated with preclinical cognitive aging. Higher baseline cognition was protective of DunedinPACE‐associated cognitive decline. The DunedinPACE association with cognitive decline explained a fourth of dementia risk.
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spelling doaj-art-c00813b213fc413fbd7aa79a23f5c2c92025-08-20T02:55:53ZengWileyAlzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring2352-87292024-10-01164n/an/a10.1002/dad2.70038Association of a pace of aging epigenetic clock with rate of cognitive decline in the Framingham Heart Study Offspring CohortMicah J. Savin0Haoyang Wang1Heming Pei2Allison E. Aiello3Stephanie Assuras4Avshalom Caspi5Terrie E. Moffitt6Peter A. Muenning7Calen P. Ryan8Baoyi Shi9Yaakov Stern10Karen Sugden11Linda Valeri12Daniel W. Belsky13Robert N. Butler Columbia Aging Center Mailman School of Public Health Columbia University Irving Medical Center New York New York USARobert N. Butler Columbia Aging Center Mailman School of Public Health Columbia University Irving Medical Center New York New York USARobert N. Butler Columbia Aging Center Mailman School of Public Health Columbia University Irving Medical Center New York New York USARobert N. Butler Columbia Aging Center Mailman School of Public Health Columbia University Irving Medical Center New York New York USANeuropsychology Department of Neurology Columbia University Irving Medical Center New York New York USADepartment of Psychology & Neuroscience Trinity College of Arts & Sciences Duke University Durham North Carolina USADepartment of Psychology & Neuroscience Trinity College of Arts & Sciences Duke University Durham North Carolina USAHealth Policy and Management Mailman School of Public Health Columbia University Irving Medical Center New York New York USARobert N. Butler Columbia Aging Center Mailman School of Public Health Columbia University Irving Medical Center New York New York USADepartment of Biostatistics MSPH Columbia University Irving Medical Center New York New York USAGH Sergievsky Center Department of Neurology Columbia University Irving Medical Center New York New York USADepartment of Psychology & Neuroscience Trinity College of Arts & Sciences Duke University Durham North Carolina USADepartment of Biostatistics MSPH Columbia University Irving Medical Center New York New York USARobert N. Butler Columbia Aging Center Mailman School of Public Health Columbia University Irving Medical Center New York New York USAAbstract INTRODUCTION The geroscience hypothesis proposes systemic biological aging is a root cause of cognitive decline. METHODS We analyzed Framingham Heart Study Offspring Cohort data (n = 2296; 46% male; baseline age M = 62, SD = 9, range = 25–101 y). We measured cognitive decline across two decades of neuropsychological‐testing follow‐up. We measured pace of aging using the DunedinPACE epigenetic clock. Analysis tested if participants with faster DunedinPACE values experienced more rapid cognitive decline compared with those with slower DunedinPACE values. RESULTS Participants with faster DunedinPACE had poorer cognitive functioning at baseline and experienced more rapid cognitive decline over follow‐up. Results were robust to confounders and consistent across population strata. Findings were similar for the PhenoAge and GrimAge epigenetic clocks. DISCUSSION Faster pace of aging is a risk factor for preclinical cognitive decline. Metrics of biological aging may inform risk stratification in clinical trials and prognosis in patient care. Highlights Faster DunedinPACE is associated with preclinical cognitive aging. Higher baseline cognition was protective of DunedinPACE‐associated cognitive decline. The DunedinPACE association with cognitive decline explained a fourth of dementia risk.https://doi.org/10.1002/dad2.70038agingAlzheimer's disease and related dementiasbiological agingcognitive declineDunedinPACEepigenetic clocks
spellingShingle Micah J. Savin
Haoyang Wang
Heming Pei
Allison E. Aiello
Stephanie Assuras
Avshalom Caspi
Terrie E. Moffitt
Peter A. Muenning
Calen P. Ryan
Baoyi Shi
Yaakov Stern
Karen Sugden
Linda Valeri
Daniel W. Belsky
Association of a pace of aging epigenetic clock with rate of cognitive decline in the Framingham Heart Study Offspring Cohort
Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring
aging
Alzheimer's disease and related dementias
biological aging
cognitive decline
DunedinPACE
epigenetic clocks
title Association of a pace of aging epigenetic clock with rate of cognitive decline in the Framingham Heart Study Offspring Cohort
title_full Association of a pace of aging epigenetic clock with rate of cognitive decline in the Framingham Heart Study Offspring Cohort
title_fullStr Association of a pace of aging epigenetic clock with rate of cognitive decline in the Framingham Heart Study Offspring Cohort
title_full_unstemmed Association of a pace of aging epigenetic clock with rate of cognitive decline in the Framingham Heart Study Offspring Cohort
title_short Association of a pace of aging epigenetic clock with rate of cognitive decline in the Framingham Heart Study Offspring Cohort
title_sort association of a pace of aging epigenetic clock with rate of cognitive decline in the framingham heart study offspring cohort
topic aging
Alzheimer's disease and related dementias
biological aging
cognitive decline
DunedinPACE
epigenetic clocks
url https://doi.org/10.1002/dad2.70038
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