Table 2.
Associations between three different Alzheimer’s disease polygenic risk scores (PRS) and cognitive test scores and eye movement outcomes.
| Cognitive outcome | b (95%-CI) for AD PRS Jansen | p-value | FDR-adjusted p-value | b (95%-CI) for AD PRS Wightman | p-value | FDR-adjusted p-value | b (95%-CI) for AD PRS Schwartzentruber | p-value | FDR-adjusted p-value |
|---|---|---|---|---|---|---|---|---|---|
| Outcomes - classical cognitive tasks | |||||||||
| Digit span forward [number of digits] | −0.017 (−0.048, 0.013) | 0.273 | 0.588 | 0.006 (−0.025, 0.037) | 0.693 | 0.808 | 0.001 (−0.030, 0.031) | 0.968 | 1.000 |
| Digit span backward [number of digits] | 0.016 (−0.016, 0.049) | 0.323 | 0.595 | 0.034 (0.001, 0.067) | 0.041 | 0.383 | 0.027 (−0.006, 0.059) | 0.105 | 0.368 |
| Corsi forward [number of blocks] | −0.031 (−0.058, −0.005) | 0.022 | 0.252 | −0.031 (−0.058, −0.004) | 0.025 | 0.383 | −0.038 (−0.065, −0.012) | 0.005 | 0.140 |
| Corsi backward [number of blocks] | −0.018 (−0.044, 0.008) | 0.167 | 0.585 | −0.015 (−0.041, 0.010) | 0.242 | 0.522 | −0.014 (−0.040, 0.012) | 0.281 | 0.564 |
| AVLT – immediate recall [sum of recalled words] | −0.147 (−0.371, 0.076) | 0.197 | 0.588 | −0.077 (−0.301, 0.147) | 0.499 | 0.665 | −0.114 (−0.338, 0.110) | 0.318 | 0.564 |
| AVLT – delayed recall [number of words] | −0.037 (−0.112, 0.039) | 0.340 | 0.595 | −0.034 (−0.110, 0.041) | 0.375 | 0.665 | −0.038 (−0.114, 0.037) | 0.320 | 0.564 |
| Word fluency task [number of animals] | −0.137 (−0.316, 0.043) | 0.137 | 0.548 | −0.104 (−0.283, 0.076) | 0.258 | 0.522 | −0.133 (−0.313, 0.047) | 0.146 | 0.409 |
| Trail-making test A [log s] | 0.002 (−0.001, 0.006) | 0.217 | 0.588 | 0.004 (0.000, 0.007) | 0.029 | 0.383 | 0.003 (−0.001, 0.006) | 0.097 | 0.368 |
| Trail-making test B [log s] | 0.003 (−0.001, 0.008) | 0.123 | 0.548 | 0.004 (−0.001, 0.008) | 0.084 | 0.470 | 0.004 (−0.001, 0.008) | 0.096 | 0.368 |
| MWT-B [sum of correctly recognised words] | −0.007 (−0.098, 0.085) | 0.887 | 0.920 | −0.033 (−0.125, 0.058) | 0.474 | 0.665 | −0.037 (−0.129, 0.054) | 0.423 | 0.564 |
| Outcomes - eye movement tasks | |||||||||
| Log of spatial error during fixation [log °] | 0.002 (−0.001, 0.006) | 0.250 | 0.588 | 0.002 (−0.002, 0.006) | 0.259 | 0.522 | 0.002 (−0.001, 0.006) | 0.248 | 0.564 |
| Log of saccade rate during fixation [log N/s] | −0.001 (−0.006, 0.005) | 0.845 | 0.910 | 0.001 (−0.004, 0.007) | 0.692 | 0.808 | 0.002 (−0.003, 0.008) | 0.416 | 0.564 |
| Log of blink rate during fixation [log N/s] | −0.001 (−0.003, 0.000) | 0.085 | 0.548 | −0.001 (−0.003, 0.000) | 0.143 | 0.500 | −0.001 (−0.002, 0.001) | 0.422 | 0.564 |
| Smooth pursuit velocity gain [%] | −0.145 (−0.553, 0.264) | 0.487 | 0.620 | −0.389 (−0.797, 0.019) | 0.061 | 0.427 | −0.393 (−0.801, 0.016) | 0.059 | 0.368 |
| Saccade frequency during smooth pursuit [N/s] | −0.017 (−0.033, −0.002) | 0.027 | 0.252 | −0.001 (−0.017, 0.014) | 0.857 | 0.908 | −0.003 (−0.018, 0.013) | 0.715 | 0.834 |
| Prosaccade latency [ms] | 0.889 (0.177, 1.601) | 0.014 | 0.252 | 0.407 (−0.303, 1.117) | 0.261 | 0.522 | 0.594 (−0.117, 1.305) | 0.102 | 0.368 |
| Prosaccade amplitude gain [%] | −0.085 (−0.272, 0.101) | 0.370 | 0.599 | −0.143 (−0.329, 0.043) | 0.132 | 0.500 | −0.178 (−0.364, 0.009) | 0.062 | 0.368 |
| Log of prosaccade spatial error [log %] | 0.003 (−0.003, 0.008) | 0.300 | 0.595 | 0.001 (−0.004, 0.007) | 0.669 | 0.808 | 0.003 (−0.003, 0.008) | 0.335 | 0.564 |
| Prosaccade peak velocity [°/s] | −0.925 (−2.549, 0.698) | 0.264 | 0.588 | 0.559 (−1.060, 2.178) | 0.499 | 0.665 | 0.077 (−1.544, 1.699) | 0.926 | 0.997 |
| Amplitude-adjusted peak prosaccade velocity | −0.006 (−0.022, 0.009) | 0.419 | 0.599 | 0.011 (−0.005, 0.026) | 0.179 | 0.522 | 0.007 (−0.009, 0.023) | 0.387 | 0.564 |
| Antisaccade latency [ms] | 0.563 (−0.830, 1.956) | 0.428 | 0.599 | −0.110 (−1.493, 1.273) | 0.876 | 0.908 | 0.072 (−1.314, 1.458) | 0.919 | 0.997 |
| Antisaccade amplitude gain [%] | −0.175 (−1.022, 0.672) | 0.686 | 0.768 | −0.517 (−1.357, 0.324) | 0.228 | 0.522 | −0.654 (−1.496, 0.188) | 0.128 | 0.398 |
| Log of antisaccade spatial error [log %] | 0.005 (−0.001, 0.011) | 0.133 | 0.548 | −0.002 (−0.008, 0.004) | 0.462 | 0.665 | −0.002 (−0.008, 0.004) | 0.499 | 0.635 |
| Antisaccade peak velocity [°/s] | −0.597 (−2.641, 1.447) | 0.567 | 0.690 | −0.184 (−2.213, 1.845) | 0.859 | 0.908 | −0.506 (−2.539, 1.527) | 0.626 | 0.762 |
| Amplitude-adjusted peak antisaccade velocity | 0.010 (−0.014, 0.034) | 0.405 | 0.599 | 0.018 (−0.006, 0.042) | 0.133 | 0.500 | 0.020 (−0.004, 0.044) | 0.101 | 0.368 |
| Antisaccade costs [ms] | −0.474 (−1.760, 0.812) | 0.470 | 0.620 | −0.531 (−1.806, 0.744) | 0.414 | 0.665 | −0.526 (−1.804, 0.751) | 0.419 | 0.564 |
| Antisaccade error rate [%] | 0.152 (−0.491, 0.794) | 0.644 | 0.751 | 0.243 (−0.398, 0.885) | 0.457 | 0.665 | 0.298 (−0.344, 0.941) | 0.363 | 0.564 |
The table displays the change in cognitive performance per one standard deviation increase in Alzheimer’s disease PRS for the three different PRS scores separately. The regression coefficients for each PRS were obtained from the following multivariable linear regression model: Cognitive outcome ~ b0 + PRS* b1 + age + age2 + sex + population stratification + residual error. The FDR-correction is based on 28 comparisons (27 in the table plus antisaccade correction rate) and was conducted for each PRS score separately. None of the association between PRS and cognitive performance remained significant after excluding APOE from the PRS. In bold are those associations with an unadjusted p-value below 0.05.
AD Alzheimer’s disease, b unstandardized regression coefficient, FDR false discovery rate, AVLT Auditory Verbal Learning and Memory Test, MWT-B Mehrfachwahl-Wortschatz-Intelligenztest, 95%-CI = 95%-confidence interval.