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Abstract
Objective: To investigate the effect of enriching mild cognitive impairment (MCI) clinical trials using combined markers of amyloid pathology and neurodegeneration.
Methods: We evaluate an implementation of the recent National Institute for Aging–Alzheimer's Association (NIA-AA) diagnostic criteria for MCI due to Alzheimer disease (AD) as inclusion criteria in clinical trials and assess the effect of enrichment with amyloid (A+), neurodegeneration (N+), and their combination (A+N+) on the rate of clinical progression, required sample sizes, and estimates of trial time and cost.
Results: Enrichment based on an individual marker (A+ or N+) substantially improves all assessed trial characteristics. Combined enrichment (A+N+) further improves these results with a reduction in required sample sizes by 45% to 60%, depending on the endpoint.
Conclusions: Operationalizing the NIA-AA diagnostic criteria for clinical trial screening has the potential to substantially improve the statistical power of trials in MCI due to AD by identifying a more rapidly progressing patient population.
GLOSSARY
- A+=
- amyloid positive;
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ADAS-Cog13=
- Alzheimer's Disease Assessment Scale Cognitive Subscale;
- ADNI=
- Alzheimer's Disease Neuroimaging Initiative;
- FAQ=
- Functional Assessment Questionnaire;
- HV=
- hippocampal volume;
- MCI=
- mild cognitive impairment;
- MMSE=
- Mini-Mental State Examination;
- N+=
- neurodegeneration positive;
- NIA-AA=
- National Institute for Aging–Alzheimer's Association;
- RAVLT=
- Rey Auditory Verbal Learning Test;
- SNR=
- signal-to-noise ratio
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (www.loni.usc.edu/ADNI). Therefore, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at Neurology.org.
Supplemental data at Neurology.org
- Received March 1, 2016.
- Accepted in final form June 7, 2016.
- © 2016 American Academy of Neurology
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