Changes in DNA methylation–based aging predicts brain damage and dementia and reflects life‐course cardiovascular risk
Nigus Gebremedhin Asefa, Jorge Martinez Romero, Yi‐Han Hu, Zhiguang Li, Osorio Meirelles, Djassinabaye Mbangdadji, May A. Beydoun, Sigurdur Sigurdsson, Valborg Gudmundsdottir, Thor Aspelund, Vilmundur Gudnason, Lenore LaunerAbstract
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.
METHODS
We analyzed data from the Age, Gene/Environment Susceptibility–Reykjavik Study (AGES‐RS; n = 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.
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.
DISCUSSION
These findings underscore the need for further investigation into the timing, reversibility, and pathways linking BA to brain health.