Peripheral DNA methylation, cognitive decline and brain aging: pilot findings from the Whitehall II imaging study.
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Chouliaras, L., Pishva, E., Haapakoski, R., Zsoldos, E., Mahmood, A., Filippini, N., Burrage, J., et al. (2018). Peripheral DNA methylation, cognitive decline and brain aging: pilot findings from the Whitehall II imaging study.. Epigenomics, 10 (5), 585-595. https://doi.org/10.2217/epi-2017-0132
Background: DNA methylation (DNAm) has been linked with the pathophysiology of brain ageing, cognitive impairment and dementia. Methods: The present study investigated the association between blood genome-wide DNAm profiles, cognitive dysfunction and brain magnetic resonance imaging (MRI) measures in 48 participants of the Whitehall II imaging sub-study. Results: We identified eight differentially methylated regions (DMRs) associated with cognitive impairment. Accelerated ageing based on the Hannum epigenetic clock was associated with mean diffusivity and global fractional anisotropy. We also identified modules of co-methylated loci associated with white matter hyperintensities. These co-methylation modules were enriched among pathways relevant to beta-amyloid processing and glutamatergic signalling. Conclusion: Our data support the notion that blood DNAm changes may have utility as a biomarker for cognitive dysfunction and brain ageing.
Brain, Humans, Aging, Premature, DNA, Magnetic Resonance Imaging, Pilot Projects, DNA Methylation, Epigenesis, Genetic, Functional Neuroimaging, Biomarkers, Cognitive Aging, Cognitive Dysfunction
. The study was funded by the National Institute of Health Research (NIHR) Academic Clinical Fellowship programme (ACF; LC) the Oxfordshire Health Services Research Committee (OHSRC; LC), the Oxford University Clinical Academic Graduate School (OUCAGS; LC), the UK Medical Research Council (G1001354; KPE; K013351; MK), the Gordon Edward Small’s Charitable Trust (SC008962; KPE), the HDH Wills 1965 charitable trust (charity No: 1117747; KPE), the Medical Research Council (MRC) (Grant number: MR/N027973/1; KL, EP) as part of the Joint Programme—Neurodegenerative Disease Research (JPND) grant for the EPI-AD consortium.
External DOI: https://doi.org/10.2217/epi-2017-0132
This record's URL: https://www.repository.cam.ac.uk/handle/1810/275755