. 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).


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  1. Miami: Age and Amyloid—What Has ApoE Got to Do With It?