ArticleAlzheimer's research & therapy2025
DNA methylation signature of a lifestyle-based resilience index for cognitive health.
Article in Alzheimer's research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- MethylCog predicts six-year cognitive ability beyond blood-based ADRD biomarkers.medRxiv : the preprint server for health sciences · 2026Article
- Development and validation of MethylCog, a blood DNA methylation proxy for cognition.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Nano-magnolol enhances the modulatory effects of magnolol on cognitive performance and BACE1-related biochemical changes in an STZ-induced rat model of Alzheimer's disease.Discover nano · 2026Article
- DNA methylation signature of cognitive reserve moderates CSF tau pathology in prodromal Alzheimer's disease.Research square · 2026Article
- Nutrition as a systems regulator of brain aging trajectories.Frontiers in molecular neuroscience · 2026Review
- Reframing brain aging: neuroinflammation as an interconnected network process.Frontiers in aging · 2026Review
- MethConvTransformer: A Deep Learning Framework for Cross-Tissue Alzheimer's Disease Detection.ArXiv · 2026Article
- The role of bilingualism on functional decline and neurodegeneration in distinct ADRD clinical syndromes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- DNA methylation and machine learning: challenges and perspective toward enhanced clinical diagnostics.Clinical epigenetics · 2025Review
- Neuroimmune dynamics and brain aging: mechanisms and consequences.Frontiers in aging neuroscience · 2025Review
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11 authors.
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Abstract
Cognitive resilience (CR) contributes to the variability in risk for developing and progressing in Alzheimer's disease (AD) among individuals. Beyond genetics, recent studies highlight the critical role of lifestyle factors in enhancing CR and delaying cognitive decline. DNA methylation (DNAm), an epigenetic mechanism influenced by both genetic and environmental factors, including CR-related lifestyle factors, offers a promising pathway for understanding the biology of CR. We studied DNAm changes associated with the Resilience Index (RI), a composite measure of lifestyle factors, using blood samples from the Healthy Brain Initiative (HBI) cohort. After corrections for multiple comparisons, our analysis identified 19 CpGs and 24 differentially methylated regions significantly associated with the RI, adjusting for covariates age, sex, APOE ε4, and immune cell composition. The RI-associated methylation changes are significantly enriched in pathways related to lipid metabolism, synaptic plasticity, and neuroinflammation, and highlight the connection between cardiovascular health and cognitive function. By identifying RI-associated DNAm, our study provided an alternative approach to discovering future targets and treatment strategies for AD, complementary to the traditional approach of identifying disease-associated variants directly. Furthermore, we developed a Methylation-based Resilience Score (MRS) that successfully predicted future cognitive decline in an external dataset from the Alzheimer's Disease Neuroimaging Initiative (ADNI), even after accounting for age, sex, APOE ε4, years of education, baseline diagnosis, and baseline MMSE score. Our findings are particularly relevant for a better understanding of epigenetic architecture underlying cognitive resilience. Importantly, the significant association between baseline MRS and future cognitive decline demonstrated that DNAm could be a predictive marker for AD, laying the foundation for future studies on personalized AD prevention.
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