Temporoparietal atrophy: a marker of AD pathology independent of clinical diagnosis

Abstract

Alzheimer's disease (AD) can present with non-amnestic clinical syndromes. We investigated whether there is an imaging signature of AD pathology in these atypical subjects. We identified 14 subjects that had pathological AD, a non-amnestic presentation (i.e. atypical AD), and MRI. These subjects were matched to 14 with clinical and pathological AD (i.e. typical AD), 14 with the same non-amnestic presentations with frontotemporal lobar degeneration (FTLD) pathology, and 20 controls. Voxel-based morphometry and region-of-interest (ROI) analysis were used to assess patterns of grey matter loss. Loss was observed in the temporoparietal cortex in both typical and atypical AD, and showed significantly greater loss than FTLD. However, the medial temporal lobes were more severely affected in typical AD and FTLD compared to atypical AD. A ratio of hippocampal and temporoparietal volumes provided excellent discrimination of atypical AD from FTLD subjects. Temporoparietal atrophy may therefore provide a useful marker of the presence of AD pathology even in subjects with atypical clinical presentations, especially in the context of relative sparing of the hippocampus.

Figure 1

Results of the VBM comparisons of typical AD, atypical AD and FTLD groups with controls. Results are shown on 3D renderings of the brain and representative coronal slices through the customized template.

Figure 2

Results of the conjunction analyses shown on 3D renderings of the brain. Two conjunction analyses are shown: 1) conjunction of “atypical AD versus controls” and “typical AD versus controls”, and 2) conjunction using the three clinical variants of atypical AD: “aphasic dementia versus controls”, “CBS versus controls”, and “bvFTD versus controls”.

Figure 3

Results of VBM direct comparisons between the typical and atypical AD groups, and between the atypical AD and FTLD groups. The typical AD and FTLD groups showed greater grey matter loss in the hippocampi than the atypical AD group. Conversely, the atypical AD group showed greater loss in the left putamen than the typical AD group, and greater loss in the temporoparietal cortex than the FTLD group.

Figure 4

Regions of grey matter loss in each of the different atypical clinical diagnosis groups (aphasic dementia, corticobasal syndrome and behavioral variant frontotemporal dementia) when compared to controls.

Figure 5

Box-plots with individual data points superimposed showing hippocampal, temporoparietal, medial parietal and lateral frontal volumes for the three disease groups and controls (CN). Clinical diagnoses for subjects in the atypical AD and FTLD groups are highlighted in different colors. P values represent Kruskal-Wallis testing across the typical and atypical AD groups and the FTLD group. Kruskal-Wallis testing across all four groups, including controls, showed differences for all regions (p<0.001). The horizontal lines of the boxes represent the 25^th, 50^th (median), and 75^th percentiles of the distributions. The vertical lines extending from the boxes stop at the most extreme data point within 1.5 inter-quartile ranges of the box.

Figure 6

ROC curves showing the ability of hippocampal volume, temporoparietal volume and the ratio of hippocampal to temporoparietal volume to differentiate patients in the atypical AD and FTLD groups.