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Table 1 Comparison of possible trial designs at different stages of Alzheimer's disease neurobiology

From: Alzheimer's disease therapeutic research: the path forward

  Mild AD Trial Early AD Trial Very early AD Trial
Cognitive status Mild dementia Mild cognitive impairment Cognitively normal
CDR global score 0.5 to 1 0.5 0
MMSE range 16 to 26 25 to 30 28 to 30
Biomarker for subject selection None Amyloid imaging and/or CSF Aβ42 Amyloid imaging and/or CSF Aβ42
Biomarker for subject stratification None or APOE genotype APOE genotype APOE genotype
Primary cognitive outcome measure ADAS-cog11 ADAS-cog12 (includes delayed recall) Sensitive memory and/or executive function measure
Primary global/functional outcome measure CDR-SB CDR-SB None
Analysis covariates Baseline cognition and regional brain volume Baseline cognition and regional brain volume Regional brain volume
Biomarker outcome Regional brain atrophy Regional brain atrophy Regional brain atrophy and/or amyloid measure (as surrogate endpoint)
Duration of treatment 18 months 24 months 24 to 36 months
Primary analysis Change score or slope of co-primaries: ADAS-cog11, CDR-SB Change score or slope of co-primaries: ADAS-cog12, CDR-SB Regional brain atrophy rate and cognitive decline
  1. AD = Alzheimer's disease; ADAS-cog = Alzheimer's Disease Assessment Scale-cognitive subscale; APOE, apolipoprotein E; CDR-SB = Clinical Dementia Rating 'sum of boxes'; CSF = cerebrospinal fluid; MMSE, Mini-Mental State Examination.