Table 1

Overview of randomised controlled trials of cholinesterase inhibitors which used the ADAS-Cog and a global clinical measure

TrialProportion screened to enrolledNumber studiedNumber withdrewDurationSecondary measuresComments
ADAS, Alzheimer’s Disease Assessment Scale; ADCS/ADL, Alzheimer’s Disease Cooperative Study Activities of Daily Living inventory; ADLC, Activities of daily living checklist; CDR-SB, Clinical Dementia Rating Scale—Sum of the Boxes; CGIC, Clinical Global Impression of Change; CIBI, Clinician Interview-Based Impression; CIBIS, Clinician’s Interview-Based Impression of Change Plus Caregiver Input; CMCS, Caregiver-rated Modified Crichton Scale; d, day; DAD, Disability Assessment for Dementia; FCCA, Final Comprehensive Consensus Assessment; GDS, Global Deterioration Scale; GERRI, Geriatric Evaluation of Relative’s Rating Instrument; GIS, Global Improvement Scale; IADL, Instrumental Activities of Daily Living; IDDD, Interview for Deterioration of Daily activities in Dementia; MENFIS, Mental Function Impairment Scale; MMSE, Mine-Mental State Examination; N/A, not available; NPI, Neuropsychiatric Inventory; PDS, Progressive Deterioration Scale; PSMS, Physical Self Maintenance Scale; PSQI, Pittsburg Sleep Quality Index; QoL-P, -C, Quality of Life (Patient or Caregiver)
Tacrine
Davis et al, 199236Not stated; 632 enrolled in “enrichment” phase112 placebo401 unable to calculate a “best dose”6 week titration phaseMMSE, PDS, PSMS, IADL, ADAS-Noncog, ADAS-totalIncluded a pretest “enrichment phase” (n = 632) to determine whether each patient had a “best dose” response (n = 231)
103 “best dose” (40 mg or 80 mg)16 did not enter the double blind phase2 week placebo baseline phaseGlobal measure: GCIC
6 weeks double blind phase
6 weeks open label phase
Knapp et al, 199437Not stated184 placebo59 placebo24 week titration phaseMMSE, PDS, GDS, Caregiver CGIC, IADL, FCCA, ADAS-total, ADAS-Noncog, PSMSGlobal measure: CIBI
61 80 mg/d32 80 mg/d6 week double blind phase
179 120 mg/d121 120 mg/d
239 160 mg/d172 160 mg/d
Metrifonate
Becker et al, 19962653:5123 placebo1 metrifonate3 week placebo run-inMMSE, ADLC, ADAS-cog, ADAS-totalIncluded a 3 week loading dose followed by a 9 week maintenance dose
27 2.1 mg/kg3 month double blind phaseGlobal measure: GIS
weekly doseFinal open label phase
Cummings et al, 199827Not stated120 placebo2 week screening 12 week double blind phasePSMS, MMSE, IADL, CIBIS+, GERRIIncluded a 2 week loading dose followed by a 10 week maintenance dose
121 0.2 mg/kg/d40 week optional open label phaseGlobal measure: CIBIC+
120 0.3 mg/kg/d
119 0.65 mg/kg/d
Morris et al, 199828511:408135 placebo16 placebo2 week screeningMMSE, NPI, GDS, ADAS-Noncog, CIBIS+, DADIncluded a 2 week loading dose followed by a 24 week maintenance dose
273 0.65 mg/kg/d58 0.65 mg/kg/d26 week double blind phaseGlobal measure: CIBIC+
8 week post treatment
Donepezil
Rogers et al, 199621Not stated40 placebo5 placebo12 week double blindMMSE, ADL, CDR-SB, QoL-P, QoL-CGlobal measure: CGIC
42 1 mg/d8 1 mg/d2 week placebo washout phase
40 3 mg/d2 3 mg/d
39 5 mg/d5 5 mg/d
Rogers et al, 1998a23Not stated162 placeboN/A24 week double blind phaseMMSE, CDR-SB, QoLGlobal measure: CIBIC+
154 5 mg/d6 week placebo washout phase
157 10 mg/d
Rogers et al, 1998b22Not stated153 placeboN/A12 week double blind phaseMMSE, CDR-SB, QoLGlobal measures: CIBIC+
157 5 mg/d3 week single blind washout
158 10 mg/d
Homma et al, 200024Not stated134 placebo39 withdrawals24 week double blind studyCDR-SB, CMCS, MENFISADAS-J Cog—Japanese version of the ADAS-Cog
134 5 mg/dGlobal measure: J-CGIC
Burns et al, 199925Not stated274 placeboN/A24 week double blind phaseIDDD, CDR-SB, QoLGlobal measure: CIBIC+
271 5 mg/d6 week placebo washout phase
273 10 mg/d
Rivastigmine
Rösler et al, 199930831:725239 placebo31 placebo26 weeksPDS, GDS, MMSEGlobal measure: CIBIC+
243 1–4 mg/d33 1–4 mg/d
243 6–12 mg/d79 6–12 mg/d
Corey-Bloom et al, 199829925:699235 placebo38 placebo7 week titration phasePDS, MMSE, GDSGlobal measure: CIBIC+
233 1–4 mg/d34 1–4 mg/d19 week flexible dose phase
231 6–12 mg/d82 6–12 mg/d
Galantamine
Tariot et al, 2000311178:978286 placebo46 placebo4 week placebo run-in phaseADCS/ADL, NPIGlobal measure: CIBIC+
140 8 mg/d32 8 mg/d5 month double blind phase
279 16 mg/d60 16 mg/d
273 24 mg/d61 24 mg/d
Raskind et al, 200032764:636213 placebo41 placebo4 week placebo run-in phaseADL, DADGlobal measure: CIBIC+
212 24 mg/d68 24 mg/d6 month double blind phase
211 32 mg/d89 32 mg/d
Rockwood et al, 200134534:386125 placebo12 placebo4 week placebo run-in periodNPI, ADAS-Noncog, DAD, PSQIGlobal measure: CIBIC+
261 24–32 mg/d86 24–32 mg/d3 month double blind phase
Wilcock et al, 200033753:653215 placebo29 placebo4 week placebo run-in periodDAD, 13-item ADAS-Cog, MMSEGlobal measure: CIBIC+
220 24 mg/d44 24 mg/d5 month double blind phase
218 32 mg/d55 32 mg/d
Wilkinson et al 200135Not stated87 placebo14 placebo2 week placebo run-inPDS-1Global measure: CGIC
88 18 mg/d25 18 mg/d2 week dose escalation
56 24 mg/d14 24 mg/d10 weeks on assigned dose
54 36 mg/d26 36 mg/d
Physostigmine
Van Dyck et al, 200040Not stated93 placebo11 placebo3 week dose enrichment phaseMMSE, IADL, GCICGlobal measure: CIBIC+
83 best dose17 best dose4 week placebo washout phase
12 week double blind phase
Thal et al, 1996391111:366183 placeboN/A4 week dose titration phaseMMSE, PSMS, IADLGlobal measure: CGIC
183 best dose2 week all placebo phase
6 week double blind phase
Thal et al, 199938699:475117 placebo31 placebo2 week washout periodIADL, GERRI, CGICGlobal measure: CIBIC+
176 30 mg/d110 30 mg/d9 week dose titration phase
182 36 mg/d124 36 mg/d24 week double blind phase