Table 2
Mean Changes in Primary and Secondary Outcome Measures During the 4-Year Study Period as Compared With Baselinea| Vitamin E | Memantine | Vitamin E + Memantine | Placebo | |
|---|---|---|---|---|
| ADCS-ADL | (n = 140) | (n = 142) | (n = 139) | (n = 140) |
| Mean (SD) baseline scoreb | 57.20 (14.38) | 57.77 (13.78) | 57.16 (13.59) | 56.93 (13.61) |
| Least squares mean follow-up score (95% CI) | 44.15 (41.98 to 46.32) | 42.98 (40.82 to 45.14) | 42.76 (40.58 to 44.94) | 50.00 (38.82 to 43.17) |
| Mean annual rate of functional decline (95% CI)c | −6.08 (−7.04 to −5.13) | −6.60 (−7.55 to −5.65) | −6.70 (−7.66 to −5.74) | −7.47 (−8.43 to −6.52) |
| Least squares means change (SE) | −13.81 (1.11) | −14.98 (1.10) | −15.20 (1.11) | −16.96 (1.11) |
| Mean difference compared with placebo (95% CI) | 3.15 (0.92 to 5.39) | 1.98 (−0.24 to 4.20) | 1.76 (−0.48 to 4.00) | |
| Unadjusted P valued | .006 | .08 | .12 | |
| Adjusted P value | .03 | .40 | .49 | |
| MMSE | (n = 136) | (n = 140) | (n = 136) | (n = 137) |
| Mean annual rate of cognitive declinec | −1.37 (−1.66 to −1.07) | −1.41 (−1.70 to −1.11) | −1.29 (−1.59 to −0.99) | −1.46 (−1.76 to −1.16) |
| Least squares means change (SE) | −2.97 (0.33) | −3.05 (0.33) | −2.80 (0.33) | −3.16 (0.33) |
| Mean difference compared with placebo (95% CI) | 0.19 (−0.54 to 0.92) | 0.12 (−0.61 to 0.84) | 0.37 (−0.36 to 1.10) | |
| Unadjusted P valued | .60 | .75 | .32 | |
| Adjusted P value | .84 | .84 | .84 | |
| ADAS-cog | (n = 135) | (n = 140) | (n = 136) | (n = 137) |
| Mean annual rate of cognitive declinec | 2.75 (2.12 to 3.39) | 2.94 (2.31 to 3.57) | 2.82 (2.18 to 3.46) | 3.59 (2.95 to 4.22) |
| Least squares means change (SE) | 5.97 (0.70) | 6.38 (0.70) | 6.13 (0.71) | 7.78 (0.70) |
| Mean difference compared with placebo (95% CI) | −1.80 (−3.28 to −0.33) | −1.39 (−2.85 to 0.07) | −1.65 (−3.12 to −0.17) | |
| Unadjusted P valued | .02 | .06 | .03 | |
| Adjusted P value | .10 | .25 | .14 | |
| NPI | (n = 140) | (n = 142) | (n = 139) | (n = 140) |
| Mean annual rate of increased symptomsc | 0.35 (−0.51 to 1.21) | 0.82 (−0.04 to 1.69) | 0.79 (−0.08 to 1.66) | 1.00 (0.12 to 1.87) |
| Least squares means change (SE) | 0.79 (1.00) | 1.87 (1.00) | 1.79 (1.00) | 2.26 (1.01) |
| Mean difference compared with placebo (95% CI) | −1.46 (−3.55 to 0.63) | −0.39 (−2.47 to 1.70) | −0.47 (−2.57 to 1.63) | |
| Unadjusted P valued | .17 | .72 | .66 | |
| Adjusted P value | .94 | .94 | .94 | |
| CAS | (n = 140) | (n = 142) | (n = 139) | (n = 140) |
| Mean annual rate of increased caregiver time, hc | 1.48 (0.80 to 2.15) | 2.43 (1.76 to 3.11) | 2.20 (1.52 to 2.88) | 2.26 (1.58 to 2.94) |
| Least squares means change (SE), h | 3.35 (0.78) | 5.52 (0.78) | 5.00 (0.78) | 5.14 (0.79) |
| Mean difference compared with placebo (95% CI) | −1.79 (−3.35 to −0.23) | 0.38 (−1.18 to 1.94) | −0.14 (−1.70 to 1.42) | |
| Unadjusted P valued | .02 | .63 | .86 | |
| Adjusted P value | .12 | .86 | .86 |
aAll fitted models included time as categorical variable with an unstructured covariance matrix. The test for a treatment × time interaction was not significant for any of the outcomes; therefore, the overall mean effects over the follow-up period are presented.
bBaseline scores are for those included in the outcome model. These scores do not equal mean decline plus follow-up scores because the baseline scores are actual means and the follow-up and change scores are model-estimated least squares means.
cAnnual rate of decline is calculated by dividing the least squares means change by the average follow-up time of 2.27 years for the ADCS-ADL Inventory, NPI, and CAS, and by 2.17 years, the average follow-up time for the MMSE and ADAS-cog. Average follow-up for the patient-completed questionnaires was slightly less due to the requirement for an in-person evaluation as opposed to the caregiver questionnaires, which were occasionally completed over the telephone.
dP value is unadjusted for multiple comparisons.