Changes in DNA methylation–based aging predicts brain damage and dementia and reflects life‐course cardiovascular risk
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Abstract INTRODUCTION There is well‐established evidence showing an association between accelerated biological aging (BA) and brain pathology. However, it remains unclear whether dynamic change in BA during adulthood is directly associated with brain health or primarily reflects cumulative life‐course environmental and lifestyle exposures. alz71632-sec-0010 METHODS We analyzed data from the Age, Gene/Environment Susceptibility–Reykjavik Study (AGES‐RS;= 2081), with assessments at midlife (≈50 [SD 6.3] years) and late‐life (baseline ≈76 [4.8]; follow‐up ≈81 [4.8] years). We identified individuals with substantial change in BA (measured by DunedinPACE) and examined associations with brain magnetic resonance imaging (MRI) and cognitive outcomes. Mediation analyses tested whether late‐life BA mediated associations between midlife cardiovascular health and later‐life brain health. alz71632-sec-0020 RESULTS Shifting to accelerated BA was associated with lower brain volumes and incident dementia. Associations with brain infarcts and cognitive function largely reflected cumulative life‐course exposure. alz71632-sec-0030 DISCUSSION These findings underscore the need for further investigation into the timing, reversibility, and pathways linking BA to brain health. alz71632-sec-0040 Highlights In analyses using the full sample (average associations), higher baseline DunedinPACE was strongly associated with lower brain volumes, greater likelihood of infarcts, and poorer cognitive perform
Abstract
Abstract INTRODUCTION There is well‐established evidence showing an association between accelerated biological aging (BA) and brain pathology. However, it remains unclear whether dynamic change in BA during adulthood is directly associated with brain health or primarily reflects cumulative life‐course environmental and lifestyle exposures. alz71632-sec-0010 METHODS We analyzed data from the Age, Gene/Environment Susceptibility–Reykjavik Study (AGES‐RS;= 2081), with assessments at midlife (≈50 [SD 6.3] years) and late‐life (baseline ≈76 [4.8]; follow‐up ≈81 [4.8] years). We identified individuals with substantial change in BA (measured by DunedinPACE) and examined associations with brain magnetic resonance imaging (MRI) and cognitive outcomes. Mediation analyses tested whether late‐life BA mediated associations between midlife cardiovascular health and later‐life brain health. alz71632-sec-0020 RESULTS Shifting to accelerated BA was associated with lower brain volumes and incident dementia. Associations with brain infarcts and cognitive function largely reflected cumulative life‐course exposure. alz71632-sec-0030 DISCUSSION These findings underscore the need for further investigation into the timing, reversibility, and pathways linking BA to brain health. alz71632-sec-0040 Highlights In analyses using the full sample (average associations), higher baseline DunedinPACE was strongly associated with lower brain volumes, greater likelihood of infarcts, and poorer cognitive performance at follow‐up. After excluding participants with consistentlyorDunedinPACE trajectories over follow‐up, a shift toward accelerated DunedinPACE was associated with lower brain volumes; however, associations with infarcts, small vessel disease, and cognitive performance were less evident. Baseline DunedinPACE mediated the association between midlife cardiovascular health (Life's Simple 7 composite score) and follow‐up brain volumes, infarcts, and cognitive performance at follow‐up. Our findings underscore the potential of biological aging not only to identify individuals at elevated risk of brain damage when their pace of aging accelerates, but also to capture the cumulative effects of lifestyle and environmental exposures on brain aging. bullet alz71632-list-0001 highlights