Effectiveness of Cholinesterase Inhibitors and Memantine for Treating Dementia: Evidence Review for a Clinical Practice Guideline

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   Figure 1. Study flow diagram.

   The term companion refers to multiple reports from a single study. The authors considered the first published study as the main paper and referred to all associated reports as “companion papers.” DSM = Diagnostic and Statistical Manual of Mental Disorders; ICD = International Classification of Diseases; NINCDS = National Institute of Neurological and Communicative Disorders and Stroke.
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   Figure 2. Summary estimates for the change in Alzheimer's Disease Assessment Scale–cognitive subscale (ADAS-cog) scores.

   For donepezil (10 mg/d) versus placebo (Alzheimer disease [AD], all severity levels), the estimate was statistically significant (P < 0.001) and tests for heterogeneity were not significant (I² = 0.0%; P = 0.94). For donepezil (10 mg/d) versus placebo (mild cognitive impairment), the estimate was not significant (P = 0.31) and tests for heterogeneity were significant (I² = 75.5%; P = 0.043). For donepezil (10 mg/d) versus placebo (mild to moderate vascular dementia), the estimate was significant (P < 0.001) and tests for heterogeneity were not significant (I² = 0.0%; P = 0.84). For galantamine (24 mg) versus placebo (mild to moderate AD), the estimate was significant (P < 0.001) and tests for heterogeneity were significant (I² = 75.5%; P = 0.001). For galantamine (24 mg) versus placebo (mild to moderate AD and vascular dementia), the estimate was significant (P < 0.001). For rivastigmine (6 mg and 12 mg) versus placebo (AD, all severity levels), the estimate was significant (P < 0.001) and tests for heterogeneity were significant (I² = 90.8%; P < 0.001). For memantine (20 mg) versus placebo (mild to moderate AD), the estimate was not significant (P = 0.25). For memantine (20 mg) versus placebo (mild to moderate vascular dementia), the estimate was significant (P < 0.001) and tests for heterogeneity were not significant (I² = 11.4%; P = 0.29).
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   Figure 3. Summary relative risks for improvement or stabilization from baseline on the clinician-based impression of change scale, with caregiver input.

   For donepezil versus placebo (Alzheimer disease [AD], all severity levels), the relative risk (RR) for improvement was statistically significant (P < 0.001) and tests for heterogeneity were not significant (I² = 0.0%; P = 0.762). For donepezil versus placebo (AD, all severity levels), the RR for improvement or stabilization was significant (P < 0.001). For donepezil versus placebo (mild to moderate vascular dementia), the RR for improvement or stabilization was not significant (P = 0.633) and tests for heterogeneity were not significant (I² = 55.1%; P = 0.136). For galantamine versus placebo (mild to moderate AD), the RR for improvement or stabilization was significant (P < 0.001) and tests for heterogeneity were not significant (I² = 19.9%; P > 0.20). For galantamine versus placebo (mild to moderate AD and vascular dementia), the RR for improvement or stabilization was significant (P = 0.002). For memantine versus placebo (AD, all severity levels), the RR for improvement was significant (P < 0.001) and tests for heterogeneity were not significant (I² = 0.0%; P > 0.20). For memantine versus placebo (AD, all severity levels), the RR for improvement or stabilization was significant (P < 0.001) and tests for heterogeneity were not significant (I² = 13.8%; P > 0.20). For rivastigmine versus placebo (AD, all severity levels), the RR for improvement or stabilization was not significant (P = 0.114).