IC-P2-118: Altered fMRI activity but not significant atrophy in the posteromedial cortices in mild cognitive impairment

Abstract

Hypometabolism of the posteromedial cortices has been consistently demonstrated early in the course of Alzheimer's disease (AD) in previous FDG-PET studies, whereas results regarding structural atrophy in the posteromedial cortices have been variable. Similar to FDG-PET, recent fMRI studies have shown alterations in posteromedial cortical function in AD and in subjects with Mild Cognitive Impairment (MCI). Combined MRI/fMRI studies reporting findings in the posteromedial cortices are, however, scarce. To investigate both structural and functional changes in the posteromedial cortices within a group of elderly individuals spanning a cognitive range from healthy aging to AD. Twenty-one older controls (OC), 18 amnestic MCI subjects and 16 AD patients underwent structural MRI and fMRI during a wordlist learning task. A T1-weighted MP-RAGE was used to acquire structural and a T2*-weighted GE-EPI sequence to acquire functional data. Whole-brain structural data analysis was performed using an optimized voxel-based morphometry (VBM) protocol. Relative changes in posteromedial cortical activity during fMRI task-performance (“task-induced deactivation responses”) were examined by contrasting visual fixation to active processing of novel plus repeated words. VBM and fMRI analyses were performed using SPM2. Threshold for statistical significance was defined as cluster-corrected p<0.05. VBM revealed significant atrophy in the MTL but not in the posteromedial cortices in MCI compared to OC, while clinical AD patients demonstrated widespread atrophy in the posteromedial cortices relative to OC. FMRI revealed significant bilateral posteromedial activity in OC but only restricted areas of activity in unilateral cingulate and precuneal cortices in MCI and AD, correspondingly. The within-group fMRI results were confirmed in the between-group analyses demonstrating impaired posteromedial cortical function in MCI, as well as in AD, compared to OC. Dysfunction of the posteromedial cortices was found already in subjects with amnestic MCI compared to healthy elderly individuals. Notably, we did not detect significant posteromedial cortical atrophy within this group of MCI subjects. In clinical AD patients, both widespread atrophy and dysfunction of the posteromedial cortices were observed. These MRI/fMRI results suggest that functional alterations precede and/or exceed macroscopic structural changes in the posteromedial cortices at the stages of amnestic MCI.