Racial disparities in the association of epigenetic age acceleration with the transition between normal cognition, mild cognitive impairment and dementia

Abstract

Background

This study aimed to explore the association between epigenetic age acceleration and the transition between different cognitive status during dementia process. We also verified the racial disparities in the above relationships.

Methods

Data was from the US Health and Retirement Study, involving 3593 participants (50+) with a 4-year follow-up. Normal cognition (NC), mild cognitive impairment (MCI) and dementia was evaluated by the modified Telephone Interview for Cognitive Status. Epigenetic age was determined by epigenetic clocks based on DNA methylation patterns and dichotomized into acceleration and deceleration according to residual from the regression of epigenetic age on chronological age. Cox regression models were conducted to examine the association between epigenetic age acceleration and risk of transition between NC, MCI and dementia. Subgroup analysis was conducted to verify racial disparities.

Results

Among those with NC at baseline (n = 2671), 1053 (39.42 %) were male, 1618 (60.58 %) were female, 2057 (77.01 %) were Whites, and 614 (22.99 %) were Non-Whites. A total of 278 participants developed the transition from NC to MCI and 42 participants developed the transition from NC to dementia during the median follow-up of 3.92 years (interquartile range: 1.17–4.83 years). Accelerated epigenetic aging measured by GrimAge clock was associated with higher risk of MCI incidence (HR = 1.56, 95 % CI: 1.15–2.11) whereas epigenetic age acceleration measured by all the seven epigenetic clocks and the risk of transition from NC to dementia was not associated. Among those with MCI at baseline (n = 922), 408 (44.25 %) were male, 514 (55.75 %) were female, 633 (68.66 %) were Whites, and 289 (31.34 %) were Non-Whites. A total of 132 participants experienced transition from MCI to dementia during the median follow-up of 3.58 years (interquartile range: 1.17–4.67 years). Participants with age acceleration measured by Horvath's skin&blood clock had a higher risk of transition from MCI to dementia (HR = 1.62, 95 % CI: 1.09–2.40). Heterogeneity of race was found in the relationship of epigenetic aging with transition between cognitive status and the observed associations only existed among non-Whites. Specifically, associations between GrimAge AccelAge and higher risk of transition from NC to MCI (HR = 2.04, 95 % CI: 1.10–3.79, P for interaction = 0.039) as well as transition from NC to dementia (HR = 3.71, 95 % CI: 1.03–13.34, P for interaction = 0.040) were only found among Non-White participants. In addition, significant association between epigenetic age acceleration measured by Hannum (HR = 2.16, 95 % CI: 1.10–4.24, P for interaction = 0.048), Horvath's skin&blood (HR = 4.33, 95 % CI: 2.04–9.20, P for interaction = 0.046), and Zhang's clock (HR = 1.94, 95 % CI: 1.07–3.51, P for interaction = 0.046), and the higher risk of the transition from MCI to dementia was only observed in non-White respondents.

Conclusions

Exposure to accelerated epigenetic aging was significantly associated with a higher risk of transition from NC to MCI as well as progression from MCI to dementia. Early detection of the differences between chronological aging and epigenetic aging and more emphasis on non-White older adults were recommended.