Okonkwo O, Oh J, Christian B, Xu G, Cleary C, Harding S, Wooten D, Hillmer A, Murali D, Barnhart T.
Fibrillar Amyloid-Β Burden in Cognitively Normal Middle-Aged Adults Enrolled in the Wisconsin Registry for Alzheimer’s Prevention.
Human Amyloid Imaging Abstract. 2012 Jan 1;
Background: Aggregation of amyloid-beta (Aβ) is a core neuropathological feature of Alzheimer’s disease (AD). However, it is unknown how early in the disease process this aggregation begins. We present initial data from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) addressing this question.
Methods: Participants (mean age=59 years% female) were cognitively-healthy middle aged adults with (FH+, n=108) or without (FH-, n=48) parental family history of AD. Participants underwent neuroimaging including an SPGR MRI (GET) and a dynamic0-minute PiB PET (Siemens HR+), and comprehensive neuropsychological examination including the Rey Auditory Verbal Learning Test (RAVLT). PiB images were co-registered to the MRI images, and Logan distribution volume ratios (DVRs) were computed utilizing a cerebellar reference derived from FreeSurfer. FreeSurfer parcellations were also used to quantify PiB retention in4 regions of interest (ROI), with specific focus on the inferior parietal lobule, the cingulate isthmus, the precuneus, the rostral middle frontal gyrus, and the superior temporal gyrus. Participants were designated as PiB+ if the mean DVR in any ROI was ≥.2.
Results: Twenty-eight percent (n=44) of the participants were PiB+. Compared to PiB- participants, PiB+ participants were more likely to be APOE4 positive (55% vs.8%, p=.002) and women (80% vs.3%, p=.052). Surprisingly, we found significant positive correlations between RAVLT Total, Short Delay, and Long Delay scores and PiB retention in the precuneus and cingulate isthmus (r’s ranging from .16 to .27, p<.05>Conclusion: We found evidence for Aβ aggregation in8% of cognitively-healthy late-middle aged adults and this was significantly influenced by APOE status and gender. The positive association with scores on cognitive tests of memory suggests that a compensatory process may be occurring. We are investigating associations between PiB amyloid burden and CSF markers of Aβ, as well as concurrent associations with FDG metabolism and BOLD signal.