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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.