Fleisher A, Esque J, Chen K, Monarrez C, Liu X, Lee W, Roontiva A, Thiyyagura P, Langbaum J, Bandy D.
Tracking Fibrillar Amyloid Accumulation and Estimating Prevention Trial Sample Sizes in Cognitively Normal APOE E4 Homozygotes, Heterozygotes and Non-Carriers.
Human Amyloid Imaging Abstract. 2012 Jan 1;
Background: We previously used Pittsburgh Compound B positron emission tomography (PiB PET) to characterize and compare baseline fibrillar amyloid measurements in cognitively normal late middle-aged and older adult apolipoprotein-E4 (APOE4) homozygotes, heterozygotes and non-carriers (Reiman et al,009). Here, we used PiB PET to track the4-month accumulation of fibrillar amyloid in these genetic groups and estimate the number of at-risk persons needed to detect attenuation in amyloid accumulation in4-month pre-symptomatic Alzheimer’s disease (AD) trials.
Methods:0 min dynamic PET scans were acquired at baseline and4-month follow-up. Cerebral-to-cerebellar PiB distribution volume ratios (DVR) were calculate in twenty-nine3±4 year-old cognitively normal participants, including APOE4 homozygotes, heterozygotes, and3 non-carriers. SPM8 was used to characterize and compare brain maps of4-month PiB DVR increases, as well as increases in six automatically labeled regions-of-interest (ROIs). The number of cognitively normal homozygotes and/or heterozygotes needed per group to detect a5% slowing in amyloid accumulation with two-tailed p=0.05,0% power was estimated.
Results: While the APOE4 homozygotes were slightly younger (p=0.05), the three genetic groups did not differ in their gender distribution, educational level, clinical ratings or neuropsychological test scores, or in their4-month cognitive test ratings and changes scores. The APOE4 homozygotes and heterozygotes had significant4-month PiB DVR increases compared to non-carriers, evident in the statistical brain maps, ROIs, and mean cerebral measurements (pConclusions: This study demonstrates increased rates of amyloid accumulation in cognitively normal adults at three levels of genetic risk for AD. A relatively small number of at-risk subjects may be needed to detect amyloid-modifying treatment effects in pre-symptomatic AD trials, as we have proposed in the Alzheimer’s Prevention Initiative (API).