Table 1 |
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Comparison of possible trial designs at different stages of Alzheimer's disease neurobiology |
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Mild AD Trial |
Early AD Trial |
Very early AD Trial |
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Cognitive status |
Mild dementia |
Mild cognitive impairment |
Cognitively normal |
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CDR global score |
0.5 to 1 |
0.5 |
0 |
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MMSE range |
16 to 26 |
25 to 30 |
28 to 30 |
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Biomarker for subject selection |
None |
Amyloid imaging and/or CSF Aβ42 |
Amyloid imaging and/or CSF Aβ42 |
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Biomarker for subject stratification |
None or APOE genotype |
APOE genotype |
APOE genotype |
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Primary cognitive outcome measure |
ADAS-cog11 |
ADAS-cog12 (includes delayed recall) |
Sensitive memory and/or executive function measure |
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Primary global/functional outcome measure |
CDR-SB |
CDR-SB |
None |
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Analysis covariates |
Baseline cognition and regional brain volume |
Baseline cognition and regional brain volume |
Regional brain volume |
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Biomarker outcome |
Regional brain atrophy |
Regional brain atrophy |
Regional brain atrophy and/or amyloid measure (as surrogate endpoint) |
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Duration of treatment |
18 months |
24 months |
24 to 36 months |
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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 |
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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. |
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Aisen Alzheimers Res Ther 2009 1:2 doi:10.1186/alzrt2 |
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