Sample Size Estimation for Alzheimer's Disease Trials from Japanese ADNI Serial Magnetic Resonance Imaging.

BACKGROUND: Little is known about the sample sizes required for clinical trials of Alzheimer's disease (AD)-modifying treatments using atrophy measures from serial brain magnetic resonance imaging (MRI) in the Japanese population.

OBJECTIVE: The primary objective of the present study was to estimate how large a sample size would be needed for future clinical trials for AD-modifying treatments in Japan using atrophy measures of the brain as a surrogate biomarker.

METHODS: Sample sizes were estimated from the rates of change of the whole brain and hippocampus by the k-means normalized boundary shift integral (KN-BSI) and cognitive measures using the data of 537 Japanese Alzheimer's Neuroimaging Initiative (J-ADNI) participants with a linear mixed-effects model. We also examined the potential use of ApoE status as a trial enrichment strategy.

RESULTS: The hippocampal atrophy rate required smaller sample sizes than cognitive measures of AD and mild cognitive impairment (MCI). Inclusion of ApoE status reduced sample sizes for AD and MCI patients in the atrophy measures.

CONCLUSION: These results show the potential use of longitudinal hippocampal atrophy measurement using automated image analysis as a progression biomarker and ApoE status as a trial enrichment strategy in a clinical trial of AD-modifying treatment in Japanese people.