Table 2.
Mean difference between ChEIs, memantine, and placebo in cognitive, global, functional, and behavioral outcomes from meta-analyses of clinical trials
| Cognitive Function (ADAS-cog or SIB) | Global (CIBIC-Plus or CDR) | Function | Behavior (NPI) | ||||||
| Monotherapy versus placebo | |||||||||
| Tan et al. [28] 23 trials; patients with mild, moderate, or severe AD | Donepezil 5 mg | –1.95 (– 2.60 to – 1.29)*** | ND | 1.00 (– 0.53 to 2.53) | ND | ||||
| Donepezil 10 mg | –2.48 (– 3.23 to – 1.73)*** | ND | 1.03 (0.21 to 1.85)* | –2.72 (– 4.92 to – 0.52)* | |||||
| Galantamine 24 mg | –3.03 (– 3.66 to – 2.41)*** | ND | 0.68 (0.04 to 1.32)* | –1.72 (– 3.12 to – 0.33)* | |||||
| Galantamine 32 mg | –3.20 (– 4.36 to – 2.04)*** | ND | ND | ND | |||||
| Rivastigmine 12 mg | –2.01 (– 2.69 to – 1.32)*** | ND | 1.80 (0.20 to 3.40)* | –0.50 (– 2.68 to 1.68) | |||||
| Memantine 20 mg | –1.29 (– 2.30 to – 0.28)* | ND | 1.02 (0.27 to 1.78)** | –0.71 (– 1.98 to 0.55) | |||||
| Birks [30] 13 trials; patients with mild, moderate, or severe AD | ChEIs pooleda | –2.37 (– 2.73 to – 2.02)*** | 1.84 (1.47 to 2.30)*** | 2.46 (1.55 to 3.37)*** | –2.44 (– 4.12 to – 0.76)** | ||||
| Donepezilb | From: – 2.33 to – 2.92 | From: 1.62 to 2.08 | 3.80 | From: 2.60 to – 5.60 | |||||
| Galantamineb | From: – 2.90 to – 3.90 | ND | ND | –2.00 | |||||
| Rivastigmineb | From: – 1.10 to – 1.60 | ND | From: 0.80 to 3.40 | ND | |||||
| Hansen et al. [29] 22 trials; patients with mild, moderate, or severe AD | Donepezil pooledc | –2.67 (– 3.28 to – 2.06)np | ND | 0.31 (0.21 to 0.40)np | –4.3 (– 5.95 to – 2.65)np | ||||
| Galantamine pooledc | –2.76 (– 3.17 to – 2.34)np | ND | 0.27 (0.18 to 0.36)np | –1.44 (– 2.39 to – 0.48)np | |||||
| Rivastigmine pooledc | –3.01 (– 3.80 to – 2.21)np | ND | 0.26 (0.11 to 0.40)np | ND | |||||
| Combination versus ChEI monotherapy | |||||||||
| Schmidt et al. [69] 4 trials; patients with moderate or severe AD | Memantine + ChEI | –0.27 (– 0.37 to – 0.17)*** | –0.20 (– 0.31 to – 0.09)*** | –0.08 (– 0.18 to 0.02) | –0.19 (– 0.31 to – 0.07)** | ||||
| Matsunaga et al. [68] 7 trials; patients with mild, moderate, or severe AD | Memantine + ChEI | –0.13 (– 0.26 to 0.01) | –0.15 (– 0.28 to – 0.01)* | –0.10 (– 0.19 to – 0.01)* | –0.13 (– 0.24 to – 0.02)* | ||||
| Tsoi et al. [71] 14 trials; patients with mild, moderate, or severe AD | Memantine + ChEI | ND | 0.01 (– 0.25 to 0.28) | –0.14 (– 1.23 to 0.95) | –1.85 (– 4.83 to 1.13) | ||||
| Combination versus memantine monotherapy | |||||||||
| Tsoi et al. [71] 14 trials; patients with mild, moderate, or severe AD | Memantine + ChEI | ND | ND | –0.39 (– 1.01 to 0.23) | ND | ||||
AD, Alzheimer’s disease; ADAS-cog, Alzheimer’s Disease Assessment Scale cognitive subscale; CDR, Clinical Dementia Rating scale; ChEI, cholinesterase inhibitor; CIBIC-Plus, Clinician’s Interview-Based Impression of Change Plus caregiver input; ND, not determined; NPI, neuropsychiatric inventory; SIB, Severe Impairment Battery. Functional outcomes based on various measures, including Alzheimer’s Disease Cooperative Study-Activities of Daily Living, Bristol Activities of Daily Living Scale, and Progressive Deterioration Scale. *p < 0.05; **p < 0.01; ***p < 0.001; npNo p value provided. aMean doses: donepezil 10 mg, galantamine 24 mg, and rivastigmine 8.5–10.4 mg. bRange of mean difference in individual studies. cDose range in individual studies: donepezil 5–10 mg, galantamine 16–32 mg, and rivastigmine 6–12 mg.