Table 2.
Relation of Epigenetic Clocks in Dorsolateral Prefrontal Cortex to Clinical Phenotypes
| EPIGENETIC CLOCKS | |||||
|---|---|---|---|---|---|
| Outcomes 1 | Hannum | Horvath | PhenoAge | GrimAge | Cortical |
| CLINICAL DIAGNOSES | Odds Ratio 2 per SD increase in clock age OR (95% CI) | ||||
| Alzheimer’s Dementia | 1.14 (0.93,1.41) | 1.03 (0.83,1.29) | 0.89 (0.74,1.07) | 0.62 (0.39,0.98) | 1.54 (1.14,2.08) |
| Any Dementia | 1.13 (0.92,1.38) | 1.00 (0.81,1.24) | 0.93 (0.78,1.12) | 0.61 (0.39, 0.96) | 1.50 (1.12,2.02) |
| COGNITIVE DECLINE |
Mean difference in annual rate of decline per SD increase in clock age2 β (p-value) |
||||
| Global cognition | −0.001 (0.9) | 0.007 (0.3) | 0.004 (0.5) | 0.036 (0.01) | −0.03 (0.003) |
| Episodic memory | −0.004 (0.6) | 0.010 (0.2) | 0.005 (0.4) | 0.031 (0.06) | −0.03 (0.02) |
| Semantic memory | −0.004 (0.6) | 0.008 (0.4) | −0.002 (0.8) | 0.041 (0.04) | −0.03 (0.04) |
| Perceptual speed | −0.002 (0.7) | 0.007 (0.3) | 0.002 (0.7) | 0.027 (0.1) | −0.03 (0.04) |
| Working memory | 0.002 (0.7) | 0.004 (0.5) | 0.002 (0.7) | 0.041 (0.01) | −0.03 (0.004) |
| Visuospatial ability | −0.004 (0.5) | −0.002 (0.7) | −0.002 (0.8) | 0.026 (0.07) | −0.03 (0.003) |
| OTHER NEUROLOGIC PHENOTYPES | |||||
| Parkinsonian signs | 0.003 (0.7) | −0.004 (0.7) | −0.003 (0.7) | −0.017 (0.4) | 0.03 (0.05) |
| Motor function | 0.001 (0.4) | 0.002 (0.4) | 0.001 (0.6) | 0.003 (0.5) | −0.001 (0.7) |
| GENETIC FACTORS |
Odds Ratio
2
per SD increase in clock age
OR (95% CI) |
||||
| ApoE e4 genotype (e3e4/e4e4) | 1.13 (0.90, 1.42) | 1.12 (0.88, 1.43) | 1.11 (0.90, 1.36) | 1.02 (0.62,1.70) | 1.49 (1.06,2.09) |
1
For Horvath, Hannum, PhenoAge, GrimAge clocks n=680 for global cognition, episodic memory, semantic memory, working memory; n=661 for perceptual speed and visuospatial ability; n=677 for Parkinsonian signs; n=635 for motor function; n=702 for Alzheimer’s dementia and 721 for dementia; n=697 for apoE. For Cortical clock we further excluded 88 participants who had been part of the original training set for the Cortical clock.
2
Odds ratios (OR) and mean differences adjusted for age at death, sex, education, and baseline levels of depressive symptoms