This is a Competing Supplement application to 1R01-AG027345 """"""""Evolution of memory-related fMRI activation over the course of MCI and AD"""""""", in order to obtain PET amyloid imaging with Pittsburgh Compound B (PIB) on a subset of subjects participating in the R01 longitudinal functional magnetic resonance imaging (fMRI) study. Both the parent R01 and this Supplement are in Response to the NIA Program Announcement (PA-04-158) for """"""""Ancillary Studies for the Alzheimer's Disease Neuroimaging Initiative (ADNI). The overall goal of the parent R01 is to develop fMRI memory paradigms as a biomarker for use in clinical trials and longitudinal studies of mild cognitive impairment (MCI) and Alzheimer's disease (AD). The goal of this Supplement is to investigate the relationship of PIB binding to alterations in memory- related fMRI activity, to determine the impact of amyloid burden on memory dysfunction in MCI and AD. We will acquire PIB and FDG PET imaging at baseline and at annual intervals to coincide with the fMRI, ASL resting perfusion, volumetric MRI, and clinical assessments in the longitudinal phase of the parent R01. We hypothesize that level of neocortical PIB binding will be associated with altered fMRI hippocampal activation and parietal deactivation in a distributed memory network, at very early stages of the pathophysiological process of AD. The level of PIB binding will correlate with degree of memory impairment at baseline and the likelihood of further memory decline. We hypothesize that the distribution of PIB retention will coincide with the pattern of hypometabolism on FDG PET and decreased resting ASL MR perfusion in specific parietal regions, and that the level of PIB binding will relate to volumetric loss on longitudinal structural MRI. The addition of PIB imaging to the parent R01 longitudinal sample provides an exceptional opportunity to further our understanding of the evolution of memory-related fMRI activity over the course of prodromal AD. It is now particularly critical to understand the relationship of amyloid to memory impairment, as potential amyloid modifying therapies are moving into large-scale clinical trials. Elucidating the contribution of amyloid burden to memory dysfunction will not only enhance our ability to use fMRI as a potential biomarker, but also add to our knowledge regarding the role of amyloid deposition in memory impairment and likelihood of clinical progression in prodromal AD. ? ? ?
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