Epigenetic Markers of Smoking Predict Brain Atrophy Independent of Self-Reported Tobacco Use and Cognitive Status
Andrea Zhang1, Burcu Kaplan2, Lily Wang1, James Galvin1, David Lukacsovich1, Deirdre O'Shea1
1University of Miami, 2University of Rhode Island
Objective:
This study investigates the association between an epigenetic marker of smoking and various measures of brain atrophy, considering self-reported tobacco use and cognitive status.
Background:
Smoking is a known risk factor for dementia, contributing to brain atrophy and cognitive decline. Traditional assessments relying on self-reported tobacco use may underestimate smoking's impact. Epigenetic markers offer a promising alternative for assessing smoking-related brain changes.
Design/Methods:
Data were obtained from 79 participants enrolled in the Healthy Brain Initiative, an ongoing longitudinal study of brain aging in older adults in South Florida, who had baseline structural MRI and blood DNA methylation data. A validated epigenetic marker of smoking was used to evaluate smoking-related changes. The analysis adjusted for age, gender, education, self-report tobacco use, cognitive status (34% MCI, 66% unimpaired), and estimated immune cell type proportions. Hierarchical multiple regression assessed the association between the epigenetic marker of smoking and several measures of brain atrophy, hippocampal volume, and white matter integrity.
Results:
The epigenetic marker explained the most variance in temporal lobe atrophy (ΔR2=.110, p=.001), followed by global atrophy (ΔR2= .093, p = .004.), frontal atrophy (ΔR2=.091, p =. 004), and hippocampal volume (ΔR2=.061, p =.028). There was no significant association between occipital or parietal lobe atrophy, white matter integrity, or total brain lesion count. The marker's association with brain atrophy measures was independent of self-reported tobacco use, which was not significantly associated with any MRI variables. Additionally, cognitive status (34% MCI) did not moderate the relationship between the epigenetic marker and MRI measures.
Conclusions:
The epigenetic marker of smoking explained a modest amount of variance in brain atrophy, most notably in the temporal lobe, independent of self-reported tobacco use, which showed no significant associations with MRI measures. These findings highlight the potential of epigenetic markers to improve brain health assessments beyond traditional self-reported measures.
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