Epigenetic aging and age-related cognitive decline both show substantial variability across individuals. While a potential link between the two is increasingly studied in both general and psychiatric populations, a systematic review has not yet been performed. This review summarizes the state of the present literature as well as critical evaluation and suggestions for future research. A literature search (October 31 th , 2024) identified original peer-reviewed studies examining epigenetic aging and cognitive function in general and/or psychiatric populations following a pre-registered protocol (PROSPERO: registration number CRD42024608024). Other article types or non-English works were excluded. 57 observational studies (N General =51, N Psychiatric =6) were included with a total number of 37,516 participants in 47 cross-sectional studies, and 15,551 within 27 longitudinal assessments. Sixteen tools of epigenetic age estimation were investigated, mainly in peripheral blood (N=53). Quality assessment with the Agency for Healthcare Research and Quality checklist showed low risk of bias in 93% of studies. Great heterogeneity existed in cohort characteristics, cognitive tests, epigenetic age assessments, use of covariates, and statistical modelling. Overall, significant associations of cognitive measures with epigenetic aging measures were found in 43 studies of which 5 included psychiatric patients. Evidence supported a link between epigenetic age acceleration and worse cognitive performance in 21/38 (55%) studies. In conclusion, current literature shows encouraging results, yet remains scarce for psychiatric populations. To establish epigenetic aging tools as biomarkers of premature cognitive aging, more research is needed. Funding: Max Planck Institute of Psychiatry. Epigenetic aging and age-related cognitive performance can substantially vary between individuals. The relationship between them is increasingly investigated in both general and psychiatric populations, yet a systematic review within these populations in the necessary detail is not available. We reviewed the literature systematically to summarize and assess existing evidence, showing the current gaps and future challenges. The evidence supports a link between epigenetic age acceleration and worse cognitive performance, yet interpretation is limited due to great methodological heterogeneity. Our work presents a critical evaluation and provides suggestions for future advancements in the field.
Yusupov et al. (Sun,) studied this question.