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. Author manuscript; available in PMC: 2024 Jan 1.
Published in final edited form as: J Alzheimers Dis. 2023;93(4):1563–1575. doi: 10.3233/JAD-230093

Table 2.

Partial Spearman correlations between second-generation DNAm markers and cognitive outcomes at baseline (n = 45)

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.

a

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.

b

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.

c

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.

d

Global cognition score is a composite score for the mean of the z-scores of all cognitive tests.

e

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.

f

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).