Table 1. Performance Differences for Cognitive Tasks for Each Drug Challenge by Treatment Type by APOE Genotype.
| Cognitive construct | Task | Dependent variable | Genotype | Treatment | 2.5 μg/kg SCOP | 5.0 μg/kg SCOP | 10 mg MECA | 20 mg MECA |
|---|---|---|---|---|---|---|---|---|
| Attention | ||||||||
| CRT | ||||||||
| Total (ms) | APOE4+ | Placebo | 21.95 (18.99) | 142.19 (35.5) | 76.16 (14.2) | 16.25 (44.4) | ||
| Tamoxifen | 31.00 (23.3) | 122.07 (43.9) | −33.63 (38.4) | 15.88 (44.1) | ||||
| APOE4− | Placebo | 23.13 (16.1) | 125.78 (32.1) | 31.34 (13.1) | 24.88 (40.6) | |||
| Tamoxifen | 87.09 (21.1) | 174.24 (37.8) | 70.33 (33.6) | 128.28 (35.4) | ||||
| Recognition RT (ms) | APOE4+ | Placebo | −2.37 (12.3) | 29.10 (16.7) | 22.91 (10.6) | −9.03 (16.3) | ||
| Tamoxifen | 6.00 (5.7) | 23.35 (16.2) | −0.50 (20.7) | 24.36 (31.4) | ||||
| APOE4− | Placebo | 16.74 (10.7) | 43.82 (15.3) | 27.35 (9.8) | 23.24 (14.9) | |||
| Tamoxifen | 10.74 (5.2) | 46.05 (14.3) | 39.41 (18.1) | 46.4 (25.7) | ||||
| Motor RT (ms) | APOE4+ | Placebo | 31.32 (14.2) | 83.25 (28.9) | 37.33 (7.3) | 17.34 (17.2) | ||
| Tamoxifen | 23.44 (25.95) | 65.33 (33.0) | −19.94 (8.9) | 2.97 (31.6) | ||||
| APOE4− | Placebo | 5.50 (11.6) | 57.74 (25.93) | 15.97 (6.7) | 20.84 (15.8) | |||
| Tamoxifen | 72.69 (23.69) | 161.08 (28.3) | 31.09 (7.8) | 85.67 (25.4) | ||||
| Short-term memory | ||||||||
| DS | ||||||||
| Digit span (number correct) | APOE4+ | Placebo | 0.86 (0.7) | −0.25 (0.6) | 0.59 (0.5) | −0.78 (0.6) | ||
| Tamoxifen | 0.25 (0.6) | −0.63 (0.6) | 0.50 (0.7) | 0.13 (0.7) | ||||
| APOE4− | Placebo | 0.33 (0.5) | −0.75 (0.5) | −0.08 (0.4) | 0.27 (0.5) | |||
| Tamoxifen | 0 (0.5) | −0.91 (0.5) | −0.28 (0.6) | −0.65 (0.6) | ||||
| Semantic memory | ||||||||
| FT | ||||||||
| Words generated | APOE4+ | Placebo | 1.29 (2.3) | −0.13 (2.1) | −2.41 (2.7) | 1.34 (2.6) | ||
| Tamoxifen | 1.13 (2.1) | −1.00 (2.1) | 1.88 (1.7) | −0.50 (2.0) | ||||
| APOE4− | Placebo | 3.63 (1.8) | 0.25 (1.8) | 0.33 (2.1) | 0.15 (2.0) | |||
| Tamoxifen | −0.18 (1.8) | −1.09 (1.8) | 1.14 (1.4) | −1.11 (1.7) | ||||
| Episodic memory | ||||||||
| SRT | ||||||||
| Total recall (number correct) | APOE4+ | Placebo | −11.68 (4.5) | −32.13 (4.2) | −7.44 (5.0) | −3.19 (3.7) | ||
| Tamoxifen | −8.00 (4.2) | −28.75 (4.2) | 3.63 (4.6) | −1.25 (3.0) | ||||
| APOE4− | Placebo | −9.50 (3.4) | −27.08 (3.4) | −6.58 (3.8) | −6.58 (3.0) | |||
| Tamoxifen | −5.14 (3.7) | −21.54 (3.7) | −6.07 (3.9) | −1.51 (2.6) | ||||
| Recall consistency (number correct) | APOE4+ | Placebo | −11.86 (4.7) | −29.25 (4.4) | −6.79 (6.2) | −1.70 (4.62) | ||
| Tamoxifen | −7.63 (4.4) | −24.75 (4.4) | 4.25 (5.9) | −1.88 (4.4) | ||||
| APOE4− | Placebo | −10.58 (3.6) | −24.42 (3.6) | −7.83 (4.8) | −7.19 (3.7) | |||
| Tamoxifen | −3.80 (4.0) | −16.70 (4.0) | −3.02 (5.1) | −0.97 (3.9) | ||||
| Recall failure (number of failures) | APOE4+ | Placebo | 8.49 (4.7) | 26.75 (4.4) | 5.74 (3.44) | 3.14 (3.3) | ||
| Tamoxifen | 6.38 (4.4) | 26.13 (4.4) | −1.75 (2.9) | 0.88 (2.7) | ||||
| APOE4− | Placebo | 6.00 (3.6) | 23.08 (3.6) | 3.00 (2.6) | 4.24 (2.6) | |||
| Tamoxifen | 5.51 (3.9) | 20.91 (3.9) | 7.12 (2.5) | 2.29 (2.4) | ||||
| Delayed recall 1 (number correct) | APOE4+ | Placebo | −2.27 (0.9) | −4.38 (0.9) | −1.00 (1.0) | −0.43 (1.04) | ||
| Tamoxifen | −2.00 (0.8) | −5.38 (0.9) | −0.38 (1.0) | 0.38 (1.0) | ||||
| APOE4− | Placebo | −2.08 (0.7) | −4.17 (0.7) | −1.50 (0.8) | −2.00 (0.83) | |||
| Tamoxifen | −0.78 (0.8) | −2.68 (0.8) | 0 (0.9) | −0.30 (0.9) | ||||
| Delayed recall 2 (number correct) | APOE4+ | Placebo | −2.51 (1.0) | −4.63 (0.9) | −1.61 (0.9) | −0.76 (0.9) | ||
| Tamoxifen | −1.50 (0.9) | −4.12 (0.9) | −0.25 (0.9) | 0.50 (0.9) | ||||
| APOE4− | Placebo | −3.50 (0.8) | −4.17 (0.8) | −1.33 (0.7) | −1.24 (0.7) | |||
| Tamoxifen | −0.92 (0.8) | −3.41 (0.8) | −0.32 (0.8) | 0.18 (0.8) | ||||
| Spatial navigation/memory | ||||||||
| MWM | ||||||||
| Platform latency hidden (s) | APOE4+ | Placebo | −0.52 (3.7) | 4.08 (5.8) | 5.88 (4.3) | 3.28 (4.3) | ||
| Tamoxifen | −4.35 (5.4) | 5.08 (4.2) | −12.09 (4.1) | 1.17 (4.2) | ||||
| APOE4− | Placebo | 2.81 (3.0) | 5.80 (4.7) | 4.86 (3.3) | −0.79 (3.3) | |||
| Tamoxifen | 1.16 (4.4) | 7.16 (3.4) | 6.05 (3.3) | 3.61 (3.3) | ||||
| Distance to platform hidden | APOE4+ | Placebo | 471.32 (479.4) | 223.04 (497.4) | 359.03 (353.4) | 146.73 (353.4) | ||
| Tamoxifen | −323.28 (607.0) | −15.68 (596.4) | −1264.77 (328.7) | −302.11 (339.5) | ||||
| APOE4− | Placebo | 493.22 (389.9) | 398.12 (406.1) | −4.74 (259.31) | 88.20 (259.3) | |||
| Tamoxifen | 14.19 (495.6) | 755.70 (486.9) | 589.83 (259.3) | 375.41 (270.8) | ||||
| APOE4+ | Placebo | −231.52 (295.6) | −474.76 (269.5) | −271.80 (353.0) | −183.76 (371.6) | |||
| Tamoxifen | 104.55 (160.8) | 138.9 (247.0) | 304.47 (216.5) | 294.85 (183.8) | ||||
| APOE4− | Placebo | −293.66 (232.3) | −212.21 (220.0) | −213.21 (251.1) | −75.60 (268.0) | |||
| Tamoxifen | 281.84 (131.3) | 383.92 (201.6) | 146.43 (165.4) | 250.74 (140.4) | ||||
| Platform latency visible (s) | APOE4+ | Placebo | 0.50 (1.2) | 0.78 (1.1) | −0.44 (0.9) | −0.52 (0.9) | ||
| Tamoxifen | 0.16 (1.1) | 2.50 (1.1) | 1.86 (0.8) | 0.32 (0.8) | ||||
| APOE4− | Placebo | −0.66 (0.9) | −0.28 (1.0) | −0.25 (0.7) | −0.80 (0.7) | |||
| Tamoxifen | 0.05 (0.9) | −0.58 (0.9) | 0.34 (0.6) | 1.16 (0.6) | ||||
| Platform distance visible | ||||||||
| APOE4+ | Placebo | 94.28 (69.8) | 57.39 (82.7) | −8.83 (106.0) | 31.04 (82.2) | |||
| Tamoxifen | 49.58 (81.9) | 27.31 (44.0) | 13.53 (42.0) | −3.51 (50.3) | ||||
| APOE4− | Placebo | −61.42 (58.7) | −21.00 (71.2) | −87.41 (75.0) | −59.46 (59.5) | |||
| Tamoxifen | 45.77 (66.9) | −52.12 (37.3) | −84.87 (32.1) | −37.42 (38.4) |
Numbers represent least squared means (standard errors) for difference scores (challenge drug minus placebo). See text for challenge drug effects. Cognitive tasks are choice reaction time (CRT) test, digit span (DS), fluency test (FT), Buschke selective reminding test (SRT), virtual Morris water maze (MWM).