P1‐412: Effects of amyloid plaques and ApoE4 allele on brain connectivity in cognitively normal elderly

At rest, important brain areas constitute a network with correlated spontaneous brain activity, the “default mode network” (DMN). These regions, including the precuneus, are among the earliest regions affected in Alzheimer's disease (AD). Both neuropathology and clinical PIB imaging studies support the existence of a pre-clinical AD state with elevated Aβ burden in cognitively normal individuals. We sought to determine if the putative toxic effects of Aβ plaques extend to differences in functional connectivity between cognitively normal individuals with (PIB+) and without (PIB-) Aβ deposition. In addition, we determined the effects of the ApoE4 allele in individuals who were PIB-. Community-living volunteers enrolled in longitudinal studies of memory and aging at the Washington University Alzheimer's Disease Research Center (ADRC). In one sample, participants with Alzheimer's disease (AD) (n = 35) were compared with 68 cognitively normal participants who were further subdivided by PET PIB imaging into those without evidence of brain amyloid (PIB-) and those with brain amyloid (PIB+) deposition. The regions with abnormalities were further applied in a sample of participants divided by ApoE genotype. Resting state fMRI (fcMRI) images were acquired on a 3T scanner and correlation maps were obtained by selecting a seed region in the precuneus and creating an image map of correlations using Pearson product-moment correlation and the voxel-by-voxel BOLD time-course. Resting state fMRI demonstrated that, compared with the PIB- group, the PIB+ group differed significantly in functional connectivity in the same regions, and in the same direction, as differences found in the AD group. Further, examining effects of ApoE4, significant differences were found in bilateral hippocampus and other regions in the default mode network. Our data demonstrate that prior to any manifestations of cognitive or behavioral changes there were differences in resting state connectivity in cognitively normal subjects with brain amyloid deposition, suggesting that early manifestation of Aβ toxicity can be detected using resting state fMRI. In addition, examining only PIB- subjects, there was a significant effect of ApoE4 genotype on connectivity, suggesting that even prior to Aβ plaque deposition, pathological effects of the E4 allele can be demonstrated.