Table 2.
Second-generation DNAm marker | Cognitive outcomes | ||||
---|---|---|---|---|---|
Primary Global cognitiond | Secondary | ||||
General cognition (3MS) | Verbal memorye | Executive function/attention scoref | |||
DNAmPhenoAgea, y | Rho | −0.10 | −0.10 | −0.01 | −0.09 |
p | 0.59 | 0.57 | 0.95 | 0.62 | |
AgeAccelPhenoa, y | Rho | −0.01 | −0.01 | 0.06 | −0.03 |
p | 0.95 | 0.94 | 0.74 | 0.86 | |
DNAmGrimAgeb, y | Rho | −0.36 | −0.10 | −0.17 | −0.32 |
p | 0.04 | 0.59 | 0.34 | 0.07 | |
AgeAccelGrimb, y | Rho | −0.40 | −0.09 | −0.19 | −0.38 |
p | 0.02 | 0.61 | 0.28 | 0.03 | |
DNAmTLc, per 100-base pairs | Rho | 0.21 | 0.04 | −0.07 | 0.28 |
p | 0.24 | 0.83 | 0.71 | 0.12 | |
DNAmTLadjAgec, per 100-base pairs | Rho | 0.16 | −0.04 | −0.12 | 0.24 |
p | 0.38 | 0.83 | 0.51 | 0.18 |
3MS, the Modified-Mini Mental State; DNAm, DNA methylation. Results of secondary cognitive outcomes were not adjusted for multiple hypothesis testing; findings should be interpreted with caution. The Spearman correlations between second-generation DNAm markers and cognitive outcomes were adjusted by chronological age, sex, blood cell proportions, body mass index, cigarette smoking, and Charlson-Deyo comorbidity index.
DNAmPhenoAge is a validated novel epigenetic clock that predicts varying aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer’s disease [4]. AgeAccelPheno is an age-accelerated residual measure of DNAmPhenoAge, derived by regressing epigenetic age on chronological age.
DNAmGrimAge is a validated novel DNAm biomarker which predicts lifespan and all-cause mortality [5]. AgeAccelGrim is an age-accelerated residual measure of DNAmGrimAge, derived by regressing epigenetic age on chronological age.
DNAmTL is a DNA methylation measurement of telomere length (unit is per 100-base pair) [6]. DNAmTLadjAge is an age-accelerated residual measure of DNAmTL, derived by regressing epigenetic age on chronological age.
Global cognition score is a composite score for the mean of the z-scores of all cognitive tests.
Verbal memory score is a composite score for the mean of the z-scores of 4 tests: the immediate and delayed recalls of a 10-word list and the East Boston Memory Test.
Executive function/attention score is a composite score for the mean of the z-scores of 4 tests: trails making tests A and B, and category fluency tests (naming animals and vegetables).