Brain DNA Methylation Age, Lifestyle Factors and Dementia in the Swedish Twin Registry.

Advanced age is the most important risk factor for dementia. Measures of biological ageing such as DNA methylation age (DNAmAge) can give more information about the accumulation of age-related molecular damage in different organs than chronological age alone. Using post-mortem brain tissue from Swedish Twin Registry participants, we explored the relationship between lifestyle factors, dementia and DNAmAge measures from prefrontal cortex and cerebellum (n = 27 individuals) and paired blood samples (n = 20 individuals). We observed that smoking was associated with a higher DNAmAge deviation (PCBrainAge + 6.4 years in prefrontal cortex, CI [2.5, 10.3], p = 0.004). Conversely, a longer time spent in formal education was associated with a lower DNAmAge deviation (DNAmClockCortical - 4.8 years in prefrontal cortex, CI [-7.9, -1.8], p = 0.007). We found no significant differences between DNAmAge deviation of dementia cases versus controls, though among dementia cases there was a tendency towards higher DNAmClockCortical deviation in prefrontal cortex for those with a more advanced Braak stage on histopathological assessment (+ 3.4 years, CI [-0.68, 7.50], p = 0.13). There were no clear associations between DNAmAge from brain and blood samples collected prior to death. In summary, these data highlight the impact of smoking and education on biomarkers of brain ageing and emphasise the role for organ-specific biomarkers of ageing.