Table 2.
Sensitivity Analysis of Efficacy (Cognitive Function) of Combination Therapy with Cholinesterase Inhibitors and Memantine
Table 2a. Prior to ADAS-cog
| Variable | Subgroup | N | n | I2 | SMD | 95% CI | P value | Test for subgroup differences |
|---|---|---|---|---|---|---|---|---|
| Placebo-controlled or Non-placebo-controlled | Placebo-controlled | 5 | 1869 | 61 | -0.1 | -0.28 to 0.03 | .1 | I2 = 0%, P = .86 |
| Non-placebo-controlled | 1 | 158 | na | -0.1 | -0.41 to 0.22 | .55 | ||
| Cholinesterase inhibitor | Donepezil | 2 | 506 | 49 | -0.3 | -0.53 to 0.04 | .09 | I2 = 0%, P = .57 |
| Rivastigmine | 1 | 158 | na | -0.1 | -0.41 to 0.22 | .55 | ||
| Others | 3 | 1363 | 58 | -0.1 | -0.24 to 0.10 | .42 | ||
| Stages of Alzheimer’s disease | Mild to moderate | 3 | 862 | 0 | 0 | -0.13 to 0.14 | .97 | I2 = 84.9%, P = .01 |
| Moderate to severe | 3 | 1165 | 16 | -0.2 | -0.38 to -0.11 | .0003 | ||
| Neuropsychological test | ADAS-cog | 3 | 862 | 0 | 0 | -0.13 to 0.14 | .97 | I2 = 74.2%, P = .02 |
| SMMSE | 1 | 112 | na | -0.1 | -0.43 to 0.32 | .77 | ||
| SIB | 2 | 1053 | 21 | -0.3 | -0.41 to -0.13 | .0001 | ||
| Sample size | Total n ≥ 200 | 4 | 1757 | 70 | -0.1 | -0.31 to 0.04 | .13 | I2 = 0%, P = .70 |
| Total n < 200 | 2 | 270 | 0 | -0.1 | -0.32 to 0.16 | .52 | ||
| Memantine dose | Memantine 20 mg | 5 | 1368 | 56 | -0.1 | -0.27 to 0.07 | .25 | I2 = 0%, P = .33 |
| Memantine 28mg extended-release | 1 | 659 | na | -0.2 | -0.36 to -0.06 | .007 | ||
| Table 2b. Prior to MMSE | ||||||||
| Variable | Subgroup | N | n | I 2 | SMD | 95% CI | P value | Test for subgroup differences |
| Placebo-controlled or Non-placebo-controlled | Placebo-controlled | 5 | 1850 | 48 | -0.2 | -0.28 to -0.02 | .03 | I2 = 64.3%, P = .09 |
| Non-placebo-controlled | 1 | 158 | na | 0.14 | -0.17 to 0.45 | .38 | ||
| Cholinesterase inhibitor | Donepezil | 2 | 506 | 49 | -0.3 | -0.53 to 0.04 | .09 | I2 = 39.3%, P = .19 |
| Rivastigmine | 1 | 158 | na | 0.14 | -0.17 to 0.45 | .38 | ||
| Others | 3 | 1344 | 33 | -0.1 | -0.24 to 0.03 | .13 | ||
| Stages of Alzheimer’s disease | Mild to moderate | 3 | 843 | 0 | 0.01 | -0.13 to 0.14 | .91 | I2 = 85.4%, P = .009 |
| Moderate to severe | 3 | 1165 | 16 | -0.2 | -0.38 to -0.11 | .0003 | ||
| Neuropsychological test | SIB | 2 | 1053 | 21 | -0.3 | -0.41 to -0.13 | .0001 | I2 = 74.9%, P = .02 |
| MMSE | 3 | 843 | 0 | 0.01 | -0.13 to 0.14 | .91 | ||
| SMMSE | 1 | 112 | na | -0.1 | -0.43 to 0.32 | .77 | ||
| Sample size | Total n ≥ 200 | 4 | 1738 | 59 | -0.2 | -0.31 to -0.01 | .04 | I2 = 56.6%, P = .13 |
| Total n < 200 | 2 | 270 | 0 | 0.06 | -0.18 to 0.30 | .63 | ||
| Memantine dose | Memantine 20 mg | 5 | 1349 | 59 | -0.1 | -0.25 to 0.09 | .36 | I2 = 17.7%, P = .27 |
| Memantine 28mg extended-release | 1 | 659 | na | -0.2 | -0.36 to -0.06 | .007 | ||
ADAS-cog, Alzheimer’s Disease Assessment Scale cognitive subscale, CI, Confidence interval, MMSE, Mini-Mental State Examination, SIB, Severe Impairment Battery, SMD, standardized mean difference, SMMSE, Standardized Mini–Mental State Examination.