Journal
NEUROBIOLOGY OF AGING
Volume 34, Issue 1, Pages 62-72Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2012.03.006
Keywords
Alzheimer's disease; Clinical trials; Mild cognitive impairment; Preclinical; Predementia; Sample size; Enrichment
Categories
Funding
- Elan
- Janssen Alzheimer Immunotherapy
- Bristol-Myers Squibb
- Medivation
- Pfizer
- Alzheimer's Disease Cooperative Study
- NIA [AG016570]
- Sidell-Kagan Foundation
- ADNI (National Institutes of Health) [U01 AG024904]
- NIA
- National Institute of Biomedical Imaging and Bioengineering
- Canadian Institutes of Health Research
- National Institutes of Health [P30 AG010129, K01 AG030514]
- Dana Foundation
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008042] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [P30AG010129, U19AG010483, P50AG016570, K01AG030514, F30AG041681, U01AG024904] Funding Source: NIH RePORTER
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This study modeled predementia Alzheimer's disease clinical trials. Longitudinal data from cognitively normal (CN) and mild cognitive impairment (MCI) participants in the Alzheimer's Disease Neuroimaging Initiative were used to calculate sample size requirements for trials using outcome measures, including the Clinical Dementia Rating scale sum of boxes, Mini-Mental State Examination, Alzheimer's Disease Assessment Scale-cognitive subscale with and without delayed recall, and the Rey Auditory Verbal Learning Task. We examined the impact on sample sizes of enrichment for genetic and biomarker criteria, including cerebrospinal fluid protein and neuroimaging analyses. We observed little cognitive decline in the CN population at 36 months, regardless of the enrichment strategy. Nonetheless, in CN subjects, using Rey Auditory Verbal Learning Task total as an outcome at 36 months required the fewest subjects across enrichment strategies, with apolipoprotein E genotype epsilon 4 carrier status requiring the fewest (n = 499 per arm to demonstrate a 25% reduction in disease progression). In MCI, enrichment reduced the required sample sizes for trials, relative to estimates based on all subjects. For MCI, the Clinical Dementia Rating scale sum of boxes consistently required the smallest sample sizes. We conclude that predementia clinical trial conduct in Alzheimer's disease is enhanced by the use of biomarker inclusion criteria. (C) 2013 Elsevier Inc. All rights reserved.
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