Table 4.
Total, direct and indirect effects of PRS for AD dementia on late-life cognitive function mediated by vascular pathologies
| Memory | Global Cognition | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Predictor | Mediator | N | Total effect (95% BCCI) |
Direct effect (95% BCCI) |
Indirect effect (95% BCCI) |
PM | Total effect (95% BCCI) |
Direct effect (95% BCCI) |
Indirect effect (95% BCCI) |
PM |
| GW-ADPRS | CMB | 2308 | −.074 (−.117, −.025) | −.072 (−.115, −.023) | −.002 (−.006, −.001) | 3.2% * | −.038 (−.081, .008) | −.034 (−.076, .013) | −.004 (−.009, −.002) | 10.8% * |
| WML | 2307 | −.078 (−.124, −.033) | −.076 (−.123, −.032) | −.002 (−.007, −.00004) | 2.7% * | −.041 (−.087, .011) | −.039 (−.085, .013) | −.002 (−.006, −.0003) | 4.0% * | |
| CAC | 2577 | −.069 (−.112, −.023) | −.067 (−.110, −.022) | −.001 (−.006, .0001) | 1.6% | −.048 (−.093, −.003) | −.046 (−.092, −.001) | −.002 (−.006, −.0001) | 4.4% * | |
| 19q13-ADPRS | CMB | 2308 | −.038 (−.087, .013) | −.035 (−.085, .017) | −.003 (−.008, −.001) | 7.4% * | −.036 (−.090, .009) | −.032 (−.079, .015) | −.004 (−.013, −.001) | 11.3% * |
| WML | 2307 | −.043 (−.091, .007) | −.041 (−.088, .010) | −.002 (−.008, −.0004) | 5.6% * | −.040 (−.091, .008) | −.038 (−.088, .012) | −.002 (−.007, −.0002) | 4.8% * | |
| CAC | 2577 | −.048 (−.096, −.001) | −.046 (−.093, .002) | −.002 (−.005, .0004) | 3.6% | −.048 (−.100, −.003) | −.045 (−.096, −.0004) | −.002 (−.006, −.0001) | 5.0% * | |
| Non-19q13ADPRS | CMB | 2308 | −.068 (−.118, −.022) | −.067 (−.116, −.020) | −.001 (−.005, −.0001) | 2.1% * | −.028 (−.075, .016) | −.026 (−.074, .019) | −.002 (−.006, −.0001) | 7.5% * |
| WML | 2307 | −.070 (−.115, −.022) | −.069 (−.114, −.021) | −.001 (−.005, .0003) | 2.0% | −.029 (−.075, .017) | −.028 (−.073, .018) | −.001 (−.005, .0003) | 3.7% | |
| CAC | 2577 | −.058 (−.102, −.013) | −.057 (−.101, −.012) | −.001 (−.004, .001) | 0.9% | −.031 (−.078, .015) | −.031 (−.077, .015) | −.001 (−.004, .001) | 2.2% | |
Predictor: GW-ADPRS, 19q13-ADPRS, and non-19q13-ADPRS (the 75th percentile vs. the 25th percentile).
Mediator: CMB (lobar cerebral microbleeds; >=2 vs. 0 or 1), WML (total brain white matter lesion load; highest quartile vs. other three quartiles of the total volume of white matter lesions), or CAC (coronary artery calcification score; log-transformed, continuous).
Outcome: z-score of the memory composite score (left panel) or z-score of the global cognition composite score (right panel).
Values for total, direct and indirect effects indicate changes in each outcome.
BCCI: bias-corrected confidence interval.
PM: proportion mediated=indirect effect beta coefficient/ total effect beta coefficient. An asterisk indicates that the PM is significantly greater than 0. Models for the effects of GW-PRS adjusted for age, sex, smoking status, midlife physical activity, and diet quality.
Models for the effects of 19q13-ADPRS adjusted for age, sex, smoking status, midlife physical activity, diet quality, and non-19q13-ADPRS.
Models for the effects of non-19q13-ADPRS adjusted for age, sex, smoking status, midlife physical activity, diet quality, and 19q13-ADPRS.
An asterisk indicates that the estimated indirect effect is significantly different from zero at the 5% level.