Background: Several studies have highlighted the evolution of functional or structural brain alterations from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD). They have pointed to a progression of brain atrophy within temporal, parietal and frontal lobes1,2 while metabolic decreases were restricted to frontal and cingulate areas3,4. Cross-sectional studies in AD led to a similar discrepancy between structural and functional alterations5. This study aims at directly assessing the relationships and differences between the profiles of metabolic and morphological changes from aMCI to AD. Methods: Seventeen aMCI patients underwent both 18FDG-PET and T1-MRI examinations at inclusion (t0) and 18 months later (t18). At t18, seven of them fulfilled clinical criteria for probable AD (converters) while the others remained clinically stable (non-converters). For MRI data, we used VBM5.1 for segmentation and DARTEL6 for a two-step warping procedure (first to an intermediate ‘t0-t18’ subject template and second to a mean group template). The t0 to t18 MRI Jacobian determinants were then used to provide grey matter (GM) evolution maps. PET data were first corrected for partial volume effects and warped onto the corresponding intermediate ‘t0-t18’ subject template where a percent of annual change (PAC) map3 was created for each patient. PET-PAC maps were then normalized onto the mean group template. Finally, voxel-by-voxel correlations were performed between the GM Jacobian and the PET-PAC maps for both converters and non-converters using the BPM toolbox7 (threshold: p<.001 uncorrected). Results: No significant positive correlations were found between PET and GM evolution maps. Significant negative correlations were found in large parieto-occipital, orbito-frontal and dorso-lateral frontal clusters for non-converters (see Figure) while no clusters reached significance for converters. Conclusions: The lack of positive correlations between PET and GM evolution maps confirms the regional discrepancy between these alterations and suggests that they are underpinned by distinct pathological processes. The negative correlation between structural and metabolic evolutions indicates that functional compensatory mechanisms may occur to face atrophy in those patients who will not rapidly decline to AD, by opposition to rapid converters. These results suggest that the inability to engage such compensatory mechanisms may be responsible for a rapid decline to AD.
References
1. Chételat et al., NeuroImage, 27, 934-46, 2005
2. Whitwell et al., Brain, 130, 1777-1786, 2007
3. Fouquet al., Brain, In Press
4. Drzezga et al., Eur J Nucl Med Mol Imaging, 30, 1104-13, 2003
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