Table 1.
Subgroup Meta-Analysis of Cholinesterase Inhibitors and Falls, Syncope, and Related Events.
| Study Characteristics (P for interaction*) | No of Studies | Treated (n / N) | Placebo (n / N) | Pooled OR (95% CI) | P for Heterogeneity | I2† |
|---|---|---|---|---|---|---|
| Fall | ||||||
| Type of cognitive impairment (P for interaction = 0.502) | ||||||
| AD | 9 | 189 / 3844 | 116 / 1953 | 0.94 (0.74, 1.20) | 0.98 | 0% |
| VD or mixed dementia | 2 | 53 / 761 | 53 / 735 | 0.99 (0.58, 1.71) | 0.18 | 44% |
| PDD or DLB | 1 | 21 / 362 | 11 / 179 | 0.94 (0.44, 2.00) | - | - |
| MCI | 1 | 61 / 1026 | 85 / 1022 | 0.70 (0.50, 0.98) | - | - |
| Severity of cognitive impairment (P for interaction = 0.263) | ||||||
| Mild | 2 | 62 / 1122 | 85 / 1079 | 0.70 (0.50, 0.99) | 0.56 | 0% |
| Mild to moderate | 7 | 206 / 4211 | 135 / 2254 | 0.91 (0.73, 1.14) | 0.81 | 0% |
| Moderate to severe | 0 | - | - | - | - | - |
| Severe | 4 | 56 / 660 | 45 / 556 | 1.08 (0.71, 1.64) | 1.00 | 0% |
| Residential status (P for interaction = 0.377) | ||||||
| Community | 10 | 281 / 5530 | 226 / 3438 | 0.85 (0.71, 1.02) | 0.81 | 0% |
| Nursing home | 3 | 43 / 463 | 39 / 451 | 1.06 (0.67, 1.69) | 1.00 | 0% |
| Length of follow-up‡ (P for interaction = 0.517) | ||||||
| < 6 months | 2 | 28 / 820 | 16 / 417 | 0.97 (0.51, 1.82) | 0.95 | 0% |
| 6 – 11 months | 11 | 253 / 4651 | 167 / 2669 | 0.98 (0.79, 1.20) | 0.79 | 0% |
| 12 – 17 months | 4 | 138 / 1200 | 98 / 808 | 0.93 (0.70, 1.22) | 0.82 | 0% |
| ≥ 18 months | 3 | 138 / 1678 | 123 / 1308 | 0.76 (0.52, 1.10) | 0.20 | 39% |
| Syncope | ||||||
| Type of cognitive impairment (P for interaction = 0.048) | ||||||
| AD | 9 | 65 / 3751 | 19 / 2137 | 1.90 (1.14, 3.15) | 0.98 | 0% |
| VD or mixed dementia | 2 | 26 / 827 | 10 / 392 | 1.19 (0.56, 2.52) | 0.33 | 0% |
| PDD or DLB | 1 | 1 / 224 | 5 / 118 | 0.10 (0.01, 0.88) | - | - |
| MCI | 1 | 4 / 391 | 1 / 387 | 3.99 (0.44, 35.9) | - | - |
| Severity of cognitive impairment (P for interaction = 0.700) | ||||||
| Mild | 4 | 31 / 1314 | 11 / 836 | 1.37 (0.69, 2.74) | 0.57 | 0% |
| Mild to moderate | 9 | 65 / 3879 | 24 / 2198 | 1.61 (0.94, 2.76) | 0.36 | 9% |
| Moderate to severe | 0 | - | - | - | - | - |
| Severe | 0 | - | - | - | - | - |
| Residential status (P for interaction = N/A) | ||||||
| Community | 13 | 96 / 5193 | 35 / 3034 | 1.53 (1.02, 2.30) | 0.53 | 0% |
| Nursing home | 0 | - | - | - | - | - |
| Length of follow-up‡ (P for interaction = 0.396) | ||||||
| < 6 months | 3 | 26 / 1480 | 7 / 805 | 1.91 (0.80, 4.58) | 0.61 | 0% |
| 6 – 11 months | 8 | 58 / 3357 | 24 / 1868 | 1.26 (0.73, 2.16) | 0.37 | 8% |
| 12 – 17 months | 3 | 13 / 368 | 4 / 367 | 2.64 (0.92, 7.59) | 0.76 | 0% |
| ≥ 18 months | 0 | - | - | - | - | - |
| Fracture | ||||||
| Type of cognitive impairment (P for interaction = 0.916) | ||||||
| AD | 6 | 22 / 1143 | 13 / 821 | 1.42 (0.69, 2.92) | 0.43 | 0% |
| VD or mixed dementia | 2 | 11 / 1071 | 4 / 519 | 1.32 (0.42, 4.16) | 0.94 | 0% |
| PDD or DLB | 0 | - | - | - | - | - |
| MCI | 0 | - | - | - | - | - |
| Severity of cognitive impairment (P for interaction = 0.861) | ||||||
| Mild | 2 | 11 / 1071 | 4 / 519 | 1.32 (0.42, 4.16) | 0.94 | 0% |
| Mild to moderate | 3 | 13 / 591 | 8 / 426 | 1.32 (0.43, 4.09) | 0.31 | 14% |
| Moderate to severe | 0 | - | - | - | - | - |
| Severe | 2 | 9 / 256 | 4 / 251 | 1.98 (0.62, 6.31) | 0.50 | 0% |
| Residential status (P for interaction = 0.482) | ||||||
| Community | 6 | 24 / 1958 | 13 / 1089 | 1.21 (0.59, 2.49) | 0.60 | 0% |
| Nursing home | 2 | 9 / 256 | 4 / 251 | 1.98 (0.62, 6.31) | 0.50 | 0% |
| Length of follow-up‡ (P for interaction = 0.882) | ||||||
| < 6 months | 3 | 6 / 739 | 1 / 428 | 1.66 (0.19, 14.4) | 0.22 | 33% |
| 6 – 11 months | 4 | 19 / 1333 | 11 / 768 | 1.22 (0.55, 2.70) | 0.65 | 0% |
| 12 – 17 months | 1 | 8 / 142 | 5 / 144 | 1.66 (0.53, 5.20) | - | - |
| ≥ 18 months | 0 | - | - | - | - | - |
| Accidental Injury | ||||||
| Type of cognitive impairment (P for interaction = 0.694) | ||||||
| AD | 14 | 324 / 5135 | 204 / 2850 | 1.20 (0.84, 1.71) | 0.002 | 59% |
| VD or mixed dementia | 4 | 160 / 1863 | 104 / 1105 | 0.96 (0.63, 1.47) | 0.07 | 58% |
| PDD or DLB | 0 | - | - | - | - | - |
| MCI | 1 | 21 / 1026 | 15 / 1022 | 1.40 (0.72, 2.74) | - | - |
| Severity of cognitive impairment (P for interaction = 0.990) | ||||||
| Mild | 5 | 162 / 2589 | 97 / 1794 | 1.06 (0.65, 1.72) | 0.04 | 60% |
| Mild to moderate | 11 | 258 / 5060 | 148 / 2812 | 1.18 (0.79, 1.75) | 0.002 | 64% |
| Moderate to severe | 2 | 78 / 247 | 72 / 251 | 1.17 (0.62, 2.19) | 0.20 | 41% |
| Severe | 1 | 7 / 128 | 6 / 120 | 1.10 (0.36, 3.37) | - | - |
| Residential status (P for interaction = 0.441) | ||||||
| Community | 17 | 431 / 7793 | 259 / 4752 | 1.10 (0.83, 1.46) | 0.001 | 58% |
| Nursing home | 2 | 74 / 231 | 64 / 225 | 1.42 (0.86, 2.33) | 0.62 | 0% |
| Length of follow-up‡ (P for interaction = 0.299) | ||||||
| < 6 months | 4 | 59 / 1601 | 23 / 845 | 1.29 (0.79, 2.11) | 0.56 | 0% |
| 6 – 11 months | 13 | 417 / 5545 | 285 / 2968 | 0.90 (0.70, 1.16) | 0.04 | 45% |
| 12 – 17 months | 4 | 104 / 1220 | 74 / 976 | 1.46 (0.79, 2.69) | 0.006 | 73% |
| ≥ 18 months | 2 | 39 / 1189 | 30 / 1098 | 0.85 (0.31, 2.32) | 0.05 | 75% |
Abbreviations: AD, Alzheimer's disease; CI, confidence interval; DLB, dementia with Lewy body; MCI, mild cognitive impairment; N/A, non-applicable; OR, odds ratio; PDD, Parkinson disease with dementia; VD, vascular dementia.
*
P value for interaction was computed from the meta-regression model that investigated the variations in effect size by a study-level characteristic.
†
I2 measures the proportion of heterogeneity in individual studies that cannot be explained by chance.
‡
Open-label extension studies of placebo-controlled trials were included so that the number of studies may be greater.