Table 3. Change from baseline in cognitive and functioning efficacy variables and brain volumes by gender and BuChE genotype (ITT-LOCF).
| Change from baseline to endpoint, mean (SD) | ||||||||
|---|---|---|---|---|---|---|---|---|
|
| ||||||||
| BuChE-K/* | BuChE wt/wt | |||||||
|
| ||||||||
| Efficacy variable | men | women | men | women | p-value1 | p-value2 | p-value3 | p-value4 |
| Number of patients (ITT) | n = 84 | n = 72 | n = 153 | n = 181 | ||||
|
| ||||||||
| Total Z-score of cognitive battery | ||||||||
| Placebo | -1.1 (4.7) | -0.9 (4.9) | -0.9 (4.1) | -0.9 (4.7) | 0.535 | 0.351 | 0.469 | 0.982 |
| Rivastigmine | -0.4 (4.7) | -0.6 (4.3) | -1.2 (4.9) | -1.0 (4.1) | 0.902 | 0.835 | ||
| p-value5 | 0.274 | 0.922 | 0.767 | 0.663 | ||||
|
| ||||||||
| ADAS-cog | ||||||||
| Placebo | -4.7 (9.7) | -2.5 (8.2) | -1.2 (5.4) | -4.1 (10.8) | 0.040 | 0.299 | 0.632 | 0.499 |
| Rivastigmine | -2.2 (8.5) | -0.9 (4.6) | -1.7 (7.9) | -3.0 (8.4) | 0.135 | 0.280 | ||
| p-value5 | 0.037 | 0.111 | 0.559 | 0.664 | ||||
|
| ||||||||
| ADCS-ADL | ||||||||
| Placebo | -5.5 (12.8) | -6.0 (12.7) | -3.4 (9.1) | -10.9 (18.2) | 0.927 | 0.002 | 0.730 | 0.014 |
| Rivastigmine | -6.9 (16.8) | -4.9 (9.7) | -5.7 (11.3) | -6.1 (14.3) | 0.739 | 0.770 | ||
| p-value5 | 0.784 | 0.769 | 0.165 | 0.046 | ||||
|
| ||||||||
| Number of patients (ITT) | n = 37 | n = 38 | n = 79 | n = 86 | ||||
|
| ||||||||
| Total hippocampal volume, cm3 | ||||||||
| Placebo | -0.3 (0.5) | -0.5 (0.6) | -0.3 (0.6) | -0.4 (0.5) | 0.727 | 0.633 | 0.714 | 0.526 |
| Rivastigmine | -0.5 (0.6) | -0.5 (0.6) | -0.2 (0.5) | -0.4 (0.7) | 0.632 | 0.162 | ||
| p-value5 | 0.681 | 0.770 | 0.448 | 0.911 | ||||
|
| ||||||||
| Annualized rates of ventricular expansion, cm3/year | ||||||||
| Placebo | 3.9 (5.7) | 7.5 (6.5) | 5.2 (6.2) | 5.7 (6.4) | 0.015 | 0.893 | 0.137 | 0.206 |
| Rivastigmine | 4.1 (3.6) | 3.6 (5.1) | 5.5 (4.5) | 3.6 (5.1) | 0.673 | 0.120 | ||
| p-value5 | 0.843 | 0.116 | 0.634 | 0.044 | ||||
|
| ||||||||
| Annualized rates of brain atrophy, cm3/year | ||||||||
| Placebo | -1.1 (10.4) | -7.2 (8.7) | -2.9 (11.1) | -5.4 (13.1) | 0.160 | 0.526 | 0.327 | 0.007 |
| Rivastigmine | -5.5 (5.9) | -4.1 (22.5) | -6.0 (6.2) | -0.6 (11.2) | 0.949 | 0.003 | ||
| p-value5 | 0.188 | 0.640 | 0.060 | 0.039 | ||||
|
| ||||||||
| Whole brain white matter volume, % change | ||||||||
| Placebo | 5.2 (6.7) | 9.1 (12.5) | 7.0 (9.9) | 6.8 (10.5) | 0.204 | 0.659 | 0.098 | 0.124 |
| Rivastigmine | 8.6 (6.1) | 4.4 (9.7) | 7.1 (6.6) | 3.0 (7.7) | 0.143 | 0.019 | ||
| p-value6 | 0.321 | 0.155 | 0.947 | 0.027 | ||||
ANCOVA model. Age, race and years of education were adjusted.
1
Men versus women in subjects with BuChE-K/*
2
Men versus women in subjects with BuChE wt/wt
3
Interaction of gender and treatment in subjects with BuChE-K/* (2-way model)
4
Interaction of gender and treatment in subjects with BuChE wt/wt (2-way model)
5
Rivastigmine versus placebo in each gender and BuChE genotype subgroup