Distinct white matter injury associated with medial temporal lobe atrophy in Alzheimer's versus semantic dementia

Abstract

This study aims at further understanding the distinct vulnerability of brain networks in Alzheimer's disease (AD) versus semantic dementia (SD) investigating the white matter injury associated with medial temporal lobe (MTL) atrophy in both conditions. Twenty-six AD patients, twenty-one SD patients, and thirty-nine controls underwent a high-resolution T1-MRI scan allowing to obtain maps of grey matter volume and white matter density. A statistical conjunction approach was used to identify MTL regions showing grey matter atrophy in both patient groups. The relationship between this common grey matter atrophy and white matter density maps was then assessed within each patient group. Patterns of grey matter atrophy were distinct in AD and SD but included a common region in the MTL, encompassing the hippocampus and amygdala. This common atrophy was associated with alterations in different white matter areas in AD versus SD, mainly including the cingulum and corpus callosum in AD, while restricted to the temporal lobe - essentially the uncinate and inferior longitudinal fasciculi - in SD. Complementary analyses revealed that these relationships remained significant when controlling for global atrophy or disease severity. Overall, this study provides the first evidence that atrophy of the same MTL region is related to damage in distinct white matter fibers in AD and SD. These different patterns emphasize the vulnerability of distinct brain networks related to the MTL in these two disorders, which might underlie the discrepancy in their symptoms. These results further suggest differences between AD and SD in the neuropathological processes occurring in the MTL. Hum Brain Mapp 38:1791-1800, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: Alzheimer's disease; hippocampus; medial temporal lobe; primary progressive aphasia; semantic dementia; white matter.

Figure 1

Significant relationships between the common medial temporal lobe atrophy (center panel) and whole‐brain white matter density maps in patients with Alzheimer's disease (top panel) and semantic dementia (bottom panel). The left panels show white matter regions associated with the right medial temporal lobe volume and the right panels show white matter regions associated with the left medial temporal lobe volume. The histograms depict the mean density of the corresponding white matter regions per group and between‐group comparisons. AD, Alzheimer's disease; L, left; NC, normal controls; R, right; SD, semantic dementia. * P < 0.05; ** P < 0.01; *** P < 0.005. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Illustration of the overlap (in red) of the relationships, in patients with Alzheimer's disease (purple) and semantic dementia (cyan), between the common left medial temporal lobe atrophy and whole‐brain white matter density maps. Similar results were obtained with the right medial temporal lobe (data not shown). [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

White matter regions in patients with Alzheimer's disease and with semantic dementia showing significant atrophy as compared with controls (red), significant relationship with the left medial temporal lobe atrophy (blue) or both (purple). Results are displayed at the same threshold of P < 0.005 uncorrected at voxel level and FWE‐corrected (P < 0.005) at cluster level. MTL, medial temporal lobe; WM, white matter. [Color figure can be viewed at http://wileyonlinelibrary.com]