MRI patterns of atrophy associated with progression to AD in amnestic mild cognitive impairment

Abstract

Objective: To compare the patterns of gray matter loss in subjects with amnestic mild cognitive impairment (aMCI) who progress to Alzheimer disease (AD) within a fixed clinical follow-up time vs those who remain stable.

Methods: Twenty-one subjects with aMCI were identified from the Mayo Clinic Alzheimer's research program who remained clinically stable for their entire observed clinical course (aMCI-S), where the minimum required follow-up time from MRI to last follow-up assessment was 3 years. These subjects were age- and gender-matched to 42 aMCI subjects who progressed to AD within 18 months of the MRI (aMCI-P). Each subject was then age- and gender-matched to a control subject. Voxel-based morphometry (VBM) was used to assess patterns of gray matter atrophy in the aMCI-P and aMCI-S groups compared to the control group, and compared to each other.

Results: The aMCI-P group showed bilateral loss affecting the medial and inferior temporal lobe, temporoparietal association neocortex, and frontal lobes, compared to controls. The aMCI-S group showed no regions of gray matter loss when compared to controls. When the aMCI-P and aMCI-S groups were compared directly, the aMCI-P group showed greater loss in the medial and inferior temporal lobes, the temporoparietal neocortex, posterior cingulate, precuneus, anterior cingulate, and frontal lobes than the aMCI-S group.

Conclusions: The regions of loss observed in subjects with amnestic mild cognitive impairment (aMCI) who progressed to Alzheimer disease (AD) within 18 months of the MRI are typical of subjects with AD. The lack of gray matter loss in subjects with aMCI who remained clinically stable for their entire observed clinical course is consistent with the notion that patterns of atrophy on MRI at baseline map well onto the subsequent clinical course.

Figure 1

Flow chart illustrating the subject selection process.

Figure 2

Schematic plot showing the time from baseline MRI to either progress to a diagnosis of AD, or the end of clinical follow-up, for all aMCI subjects. Subjects 1–21 were classified as the aMCI-S subjects that do not progress to AD over their entire follow-up, and subjects 22–63 were classified as the aMCI-P subjects since they progressed within 18 months of the MRI scan. The gray vertical lines indicate the 18 month and three year time-points.

Figure 3

Plots showing the change in MMSE, CDR sum of boxes and AVLT sum of learning over trials 1–5 over three years from the time of the MRI in the aMCI-P (black), aMCI-S (blue) and control subjects (red).

Figure 4

Patterns of grey matter loss identified in the aMCI-P group compared to controls (corrected for multiple comparisons, p<0.05). The patterns of cortical atrophy are shown on a 3D surface render (top). In addition the results are shown on a sagittal and coronal slice through the customized template, selected to highlight changes in the cingulate cortex and the medial temporal lobes (bottom). L = left; R = right

Figure 5

Regions that show greater grey matter loss in the aMCI-P group compared to the aMCI-S group (corrected for multiple comparisons, p<0.05). The patterns of cortical atrophy are shown on a 3D surface render (top). In addition the results are shown on a sagittal and coronal slice through the customized template, selected to highlight changes in the cingulate cortex and the medial temporal lobes (bottom). L = left; R = right