IC-P2-128: Twelve-month cerebral metabolic declines in probable Alzheimer's disease and amnestic mild cognitive impairment: Preliminary findings from the Alzheimer's disease neuroimaging initiative

Abstract

In a small positron emission tomography (PET) study, we previously characterized twelve-month cerebral metabolic rate for glucose (CMRgl) declines in moderate probable Alzheimer's disease (pAD) patients and estimated the number of patients needed to detect disease-modifying treatment effects in a single-center randomized clinical trial (RCT, Alexander et al, 2002). The objectives of this study are to characterize twelve-month CMRgl declines in mild pAD and amnestic mild cognitive impairment (aMCI) patients from the multi-center Alzheimer's Disease Neuroimaging Initiative (ADNI) and estimate the number of mild pAD patients and MCI patients needed to evaluate a putative disease-slowing treatment in twelve-month multi-center RCTs. SPM5 was used to characterize twelve-month declines in 17 mild pAD patients (baseline age 71±12, MMSE 24±2) and 46 aMCI patients (baseline age 66±13, MMSE 27±2). Maximal CMRgl declines were used to estimate the number of mild pAD and aMCI patients needed per group to detect disease-modifying treatment effects in six- or twelve-month multi-center RCTs with 80% power and P≤0.001 uncorrected for multiple comparisons. The pAD patients had twelve-month CMRgl declines in posterior cingulate, precuneus, parietal, temporal and frontal regions and the aMCI patients had twelve-month CMRgl declines in the posterior cingulate, precuneus, parietal and temporal regions. To detect a 20% treatment effect on posterior cingulate CMRgl declines, we estimate the need for 153 mild pAD patients per group and 728 aMCI patients per group in twelve-month RCTs. This study provides preliminary information about twelve-month CMRgl declines in mild pAD and aMCI patients and the number of patients needed to detect disease-modifying treatment effects in a twelve-month multi-center RCT. Future analyses will extend our findings to the entire ADNI cohort, provide power estimates for 6, 12, 18 and 24-month multi-center RCTs using specified search regions versus ROIs, and compare these power estimates to those using clinical ratings, other imaging modalities and other image-analysis techniques.