Evolution of global and local grey matter atrophy on serial MRI scans during the progression from MCI to AD.

Mild cognitive impairment (MCI) often represents a prodromal form of dementia, conferring a significantly higher risk of converting to probable Alzheimer's disease (AD). The aim of this study is to characterise the differences of grey matter (GM) distribution and dynamics between progressive and stable MCI subjects during a 2 year period preceding the conversion to AD. We included 48 stable MCI and 12 progressive MCI cases based on the availability of 3 serial scans acquired with approximately 1 year scan interval. For the progressive MCI group, the third scan was acquired at the time of the clinical diagnosis of AD, while the first two scans were acquired approximately 2 and 1 years earlier. For the stable MCI group, the three scans were acquired at approximately 1 year intervals during a period free from significant cognitive decline. We used longitudinal voxel-based morphometry (VBM) for mapping the progression of GM loss over time. For the progressive MCI group, the cross-sectional analysis revealed areas of lower GM volumes in the parahippocampal gyrus, precuneus and posterior cingulate 12 months before the AD diagnosis. For the longitudinal VBM analysis the progressive MCI group revealed increased GM loss in cortical regions belonging to the temporal neocortex, parahippocampal cortex, and cingulate gyrus. The frontal lobe, insula and the cerebellum were also affected. This accelerated atrophy may offer new insights into the understanding of neurodegenerative pathology and the clinical relevance of these changes remains to be verified by subsequent studies.