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

Abstract

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.

Midlife cancer/diabetes and risk of dementia and mild cognitive impairment: A population‐based prospective cohort study in Japan

“…Trained neuropsychologists assessed cognitive function using the Mini‐Mental State Examination, the Logical Memory I/II subtest of the Wechsler Memory Scale – Revised, the Clock‐Drawing Test, and the Clinical Dementia Rating Scale. According to the Japan Alzheimer's Disease Neuroimaging Initiative project, for mild cognitive impairment (MCI), the cut‐off point of the Wechsler Memory Scale – Revised Logical Memory II subtest was adjusted for education (2 for 0–9 years, 4 for 10–15 years, and 8 for >15 years). For dementia, the Mini‐Mental State Examination cut‐off point was set to 23.…”

The association between “Brain‐Age Score” (BAS) and traditional neuropsychological screening tools in Alzheimer's disease

“…We evaluated the proposed framework on 147 AD patients, 112 progressive‐MCI (pMCI) patients, 102 stable‐MCI (sMCI) patients, and 146 healthy controls (HCs) acquired from the J‐ADNI dataset. More information about J‐ADNI is provided in the Appendix and (Fujishima et al., 2017). To test the efficiency of the proposed framework, we performed a correlation test between the BAS and the neuropsychological screening tools (i.e., MMSE, CDR, ADAS, and FAQ) as well as between the BAS and anatomical MRI measurements (i.e., normalized gray matter (nGM), normalized white matter (nWM), normalized cerebrospinal fluid (nCSF), mean cortical thickness, and hippocampus volume).…”

Evaluation of PiB visual interpretation with CSF Aβ and longitudinal SUVR in J-ADNI study

“…The ApoE genotype was determined by direct sequencing [18]. Clinical Dementia Rating (CDR) was performed for assessment of the clinical status in this study.…”

“…Structural MRI was performed with 1.5-T MRI scanners using a three-dimensional sagittal magnetization-prepared rapid gradient-echo imaging (MPRAGE) sequence according to a standardized protocol [18] at each PiB follow-up period. For the 133 individuals, a total of 5 MRI scanner models by three vendors were used (34 GE SIGNA EXCITE, 17 GE SIGNA HDxt, 11 Philips Intera, 30 Siemens Avanto, 41 Siemens Symphony).…”