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. 2008 Jan 1;70(1):25-34.
doi: 10.1212/01.wnl.0000287073.12737.35.

Progressive aphasia secondary to Alzheimer disease vs FTLD pathology

K A Josephs  1 , J L Whitwell, J R Duffy, W A Vanvoorst, E A Strand, W T Hu, B F Boeve, N R Graff-Radford, J E Parisi, D S Knopman, D W Dickson, C R Jack Jr, R C Petersen
Affiliations

Progressive aphasia secondary to Alzheimer disease vs FTLD pathology

K A Josephs et al. Neurology. .

Abstract

Background: The pathology causing progressive aphasia is typically a variant of frontotemporal lobar degeneration, especially with ubiquitin-positive inclusions (FTLD-U). Less commonly the underlying pathology is Alzheimer disease (AD).

Objective: To compare clinicopathologic and MRI features of subjects with progressive aphasia and AD pathology to subjects with aphasia and FTLD-U pathology and subjects with typical AD.

Methods: We identified 5 subjects with aphasia and AD pathology and 5 with aphasia and FTLD-U pathology with an MRI from a total of 216 aphasia subjects. Ten subjects with typical AD clinical features and AD pathology were also identified. All subjects with AD pathology underwent pathologic reanalysis with TDP-43 immunohistochemistry. Voxel-based morphometry (VBM) was used to assess patterns of gray matter atrophy in the aphasia cases with AD pathology, aphasia cases with FTLD-U, and typical AD cases with AD pathology, compared with a normal control group.

Results: All aphasic subjects had fluent speech output. However, those with AD pathology had better processing speed than those with FTLD-U pathology. Immunohistochemistry with TDP-43 antibodies was negative. VBM revealed gray matter atrophy predominantly in the temporoparietal cortices, with notable sparing of the hippocampus in the aphasia with AD subjects. In comparison, the aphasic subjects with FTLD-U showed sparing of the parietal lobe. Typical AD subjects showed temporoparietal and hippocampal atrophy.

Conclusions: A temporoparietal pattern of atrophy on MRI in patients with progressive fluent aphasia and relatively preserved processing speed is suggestive of underlying Alzheimer disease pathology rather than frontotemporal lobar degeneration with ubiquitin-only immunoreactive changes.

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Figures

Figure 1
Figure 1
The patterns of grey matter loss identified by voxel-based morphometry in the aphasic subjects with AD pathology (A), the aphasic subjects with FTLD-U pathology (B), and the subjects with clinical and pathological AD (C), compared to controls (corrected for multiple comparisons, p<0.01). The results are shown both on a 3D surface render to illustrate the patterns of cortical grey matter loss, and on a representative coronal slice (y=−15) to illustrate the involvement of the hippocampus. R = right.
See this image and copyright information in PMC

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