O2-02-01: Patterns of atrophy on voxel based morphometry differ between amnestic MCI converters and nonconverters

Abstract

Amnestic mild cognitive impairment (aMCI) represents the clinically evident prodromal phase of Alzheimer's disease (AD). While the majority of aMCI subjects progress to AD, a proportion remains relatively stable. Identifying characteristics that distinguish aMCI subjects who convert more vs. less rapidly is useful for clinical and disease characterization purposes. To compare patterns of grey matter loss in subjects with aMCI who convert to AD within a fixed time interval vs. those who do not convert. Thirty-seven aMCI subjects were identified that converted to AD within 18 months of the baseline MRI scan (aMCI converters). In addition, a group of 18 aMCI subjects were identified that remained stable for their entire clinical course, where the minimum required follow-up time from baseline MRI was set at three years (aMCI non-converters). Each subject was age- and gender-matched to a control. Voxel-based morphometry (VBM) was used to assess patterns of grey matter atrophy in the aMCI converters and non-converters compared to the control group, and compared to each other. An optimized version of VBM was applied using customized templates and prior probability maps. The aMCI converters showed a bilateral pattern of loss affecting the mesial and inferior temporal lobe, the temporoparietal association neocortex and the frontal lobes, compared to controls. The aMCI non-converters showed no regions of grey matter loss when compared to controls. When the converters and non-converters were compared directly, the converters showed greater grey matter loss in the mesial and inferior temporal lobes, the temporoparietal neocortex, posterior cingulate, precuneus, anterior cingulate, and frontal lobes than the non-converters (Figure; results shown on a 3D render and on representative slices corrected for multiple comparisons using the FDR, p<0.05). The regions of loss observed in aMCI converters are typical of subjects with AD, and fit the known pattern of pathological progression in AD. The lack of grey matter loss in non-converter aMCI subjects is consistent with the notion that patterns of atrophy on MRI at baseline map well onto the subsequent clinical course.