Using serial registered brain magnetic resonance imaging to measure disease progression in Alzheimer disease - Power calculations and estimates of sample size to detect treatment effects

Objective: To evaluate the rate of brain atrophy calculated from serial mag netic resonance imaging (MRI) registration as a surrogate marker of disease progression for use in clinical trials in Alzheimer disease (AD). Methods: Eighteen patients with mild to moderate AD and 18 age-matched norm al controls underwent 2 MRI brain scans separated by a 12-month interval. E ach individual's later scan was registered to their first scan, and the vol ume of cerebral tissue loss calculated directly from the registered and sub tracted MRI scan pairs. The mean and SD of the rate of brain volume changes were used to estimate the sample sizes that would be needed in a clinical trial with a drug anticipated to modify disease progression by varying degr ees. Comparable sample size estimates were performed with data for other me thods of monitoring rates of brain atrophy, extracted from published papers . Results: The mean (SD) rate of brain atrophy for the patients with AD was 2 .37% (1.11%) per year, while in the control group it was 0.41% (0.47%) per year. Based on these figures, to have 90% power to detect a drug effect equ ivalent to a 20% reduction in the rate of atrophy, 207 patients would be ne eded in Each treatment arm. This assumes a 1-year placebo-controlled trial with a 10% patient dropout rate, and that 10% of scan pairs are unusable. Conclusion: Registration of serial MRI volume images provides a powerful me thod of quantification of brain atrophy that call be used to monitor progre ssion of AD in clinical trials.