Epigenetic aging as a biomarker of dementia and related outcomes: a systematic review

Background: Biological aging may be a robust biomarker of dementia or cognitive performance. This systematic review synthesized the evidence for an association between epigenetic aging and dementia, mild cognitive impairment and cognitive function. Methods: A systematic search was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: 30 eligible articles were included. There was no strong evidence that accelerated epigenetic aging was associated with dementia/mild cognitive impairment (n = 7). There was some evidence of an association with poorer cognition (n = 20), particularly with GrimAge acceleration, but this was inconsistent and varied across cognitive domains. A meta-analysis was not performed due to high study heterogeneity. Conclusion: There is insufficient evidence to indicate that current epigenetic aging clocks can be clinically useful biomarkers of dementia or cognitive aging. Plain language summary As individuals get older, changes in cognitive performance are common, including some degree of cognitive decline. Dementia is a symptom characterized by significant decline in cognitive function that affects daily living, and age is the biggest risk factor. Researchers have now identified ways to estimate a person's biological age from a blood sample (referred to as 'epigenetic aging'), and this measure is thought to better estimate an individual's rate of aging than his or her chronological age. This study brought together all of the previous studies, 30 in total, that have investigated links between biological aging and cognitive performance, as well as dementia risk. Synthesizing all of this evidence, the authors found no strong evidence that the individuals with dementia had accelerated aging. However, there was some evidence, although inconsistent, indicating that accelerated aging was associated with worse cognitive performance. Tweetable abstract Although age is the strongest risk factor for dementia, there is no strong evidence that individuals with dementia have accelerated biological aging (based on existing epigenetic clocks).