Table 4 Mediation analyses testing hypothesized paths (Supplementary Fig. 3). Variables significantly associated with the residual measure in bivariate analyses (Table 2) that were not included as mediators were included as covariates as were the presence/absence of subjective cognitive decline, baseline mean whole brain cortical thickness, and baseline mPACC5. Significant mediation paths (defined as bootstrapped 95% CI not including 0) are highlighted in bold
From: Axonal degeneration and amyloid pathology predict cognitive decline beyond cortical atrophy
| Â | Included potential mediators | Path | Beta (95% CI) | Standardized beta (95% CI)a |
|---|---|---|---|---|
Age | p-tau181, WML volume, NfL | Â | Â | Â |
 Direct effect |  |  | 0.003 (-0.018 to 0.026) |  |
 Total indirect effects |  |  | -0.010 (-0.022 to -0.0002) | -0.058 (-0.127 to -0.001) |
 Indirect effects |  | Age – P-tau181 – NfL – residual | -0.0006 (-0.002 to 0.0004) | -0.003 (-0.014 to 0.002) |
|  |  | Age – NfL – residual | -0.007 (-0.016 to -0.001) | -0.043 (-0.094 to -0.009) |
|  |  | Age – WML volume – NfL – residual | -0.002 (-0.004 to -0.0003) | -0.012 (-0.025 to -0.002) |
Male sex | WML volume, NfL | Â | Â | Â |
 Direct effect |  |  | 0.029 (-0.209 to 0.267) |  |
 Total indirect effect |  |  | -0.045 (-0.112 to 0.006) | -0.048 (-0.120 to 0.006) |
 Indirect effects |  | Sex – NfL – residual | -0.050 (-0.116 to -0.006) | -0.054 (-0.125 to -0.007) |
|  |  | Sex – WML volume – NfL – residual | 0.006 (-0.001 to 0.017) | 0.006 (-0.002 to 0.018) |
WML volume | NfL | Â | Â | Â |
 Direct effect |  |  | 0.004 (-0.172 to 0.181) |  |
 Total indirect effect |  |  | -0.049 (-0.101 to -0.009) | -0.034 (-0.070 to -0.006) |
 Indirect effects |  | WML volume – NfL – residual | -0.049 (-0.101 to -0.009) | -0.034 (-0.070 to -0.006) |
APOEe4 allele | Aβ42/40b, GFAP, P-tau181, NfL |  |  |  |
 Direct effect |  |  | -0.067 (-0.285 to 0.152) |  |
 Total indirect effect |  |  | -0.173 (-0.315 to -0.051) | -0.184 (-0.324 to -0.057) |
 Indirect effects |  | APOE4 – Aβ42/40 – GFAP – P-tau181 – NfL – residual | -0.0038 (-0.0087 to -0.0005) | -0.0041 (-0.010 to -0.0006) |
|  |  | APOE4 – Aβ42/40 – GFAP – NfL – residual | -0.0069 (-0.0164 to -0.001) | -0.0074-(-0.0174 to -0.0011) |
|  |  | APOE4 – Aβ42/40 – P-tau181 – NfL – residual | -0.0237 (-0.050 to -0.006) | -0.025 (-0.054 to -0.006) |
|  |  | APOE4 – Aβ42/40 – NfL – residual | 0.004 (-0.016 to 0.034) | 0.004 (-0.018 to 0.037) |
|  |  | APOE4 – Aβ42/40 – residual | -0.129 (-0.315 to -0.051) | -0.137 (-0.268 to -0.021) |