Abstract
The primary progressive aphasias (PPA) are a heterogeneous group of language-led neurodegenerative diseases resulting from large-scale brain network degeneration. White matter (WM) pathways bind networks together, and might therefore hold information about PPA pathogenesis. Here we used diffusion tensor imaging and tract-based spatial statistics to compare WM tract changes between PPA syndromes and with respect to Alzheimer's disease and healthy controls in 33 patients with PPA (13 nonfluent/agrammatic PPA); 10 logopenic variant PPA; and 10 semantic variant PPA. Nonfluent/agrammatic PPA was associated with predominantly left-sided and anterior tract alterations including uncinate fasciculus (UF) and subcortical projections; semantic variant PPA with bilateral alterations in inferior longitudinal fasciculus and UF; and logopenic variant PPA with bilateral but predominantly left-sided alterations in inferior longitudinal fasciculus, UF, superior longitudinal fasciculus, and subcortical projections. Tract alterations were more extensive than gray matter alterations, and the extent of alteration across tracts and PPA syndromes varied between diffusivity metrics. These WM signatures of PPA syndromes illustrate the selective vulnerability of brain language networks in these diseases and might have some pathologic specificity.
Highlights
The primary progressive aphasias (PPA) or ‘language-led dementias’ are important on clinical and neurobiological grounds (Gorno-Tempini et al, 2011; Grossman, 2010; Rohrer et al, 2010c)
A recent wealth of genetic and neuropathological data has enabled certain clinical PPA phenotypes to be correlated with particular pathological substrates: for example, semantic variant PPA (sv-PPA) is predominantly associated with TAR DNA-binding protein 43 (TDP-43) type C pathology and logopenic variant PPA (lv-PPA) with Alzheimer’s disease (AD) pathology (Grossman, 2010; Rohrer et al, 2011; Whitwell and Josephs, 2011)
Most patients were characterized as having nonfluent/agrammatic variant PPA (nv-PPA) (n 1⁄4 13), lv-PPA (n 1⁄4 10), or sv-PPA (n 1⁄4 10) in line with current criteria (Gorno-Tempini et al, 2011)
Summary
The primary progressive aphasias (PPA) or ‘language-led dementias’ are important on clinical and neurobiological grounds (Gorno-Tempini et al, 2011; Grossman, 2010; Rohrer et al, 2010c). A recent wealth of genetic and neuropathological data has enabled certain clinical PPA phenotypes to be correlated with particular pathological substrates: for example, sv-PPA is predominantly associated with TAR DNA-binding protein 43 (TDP-43) type C pathology and lv-PPA with Alzheimer’s disease (AD) pathology (Grossman, 2010; Rohrer et al, 2011; Whitwell and Josephs, 2011). Despite these advances, predicting tissue pathology or making an accurate clinical diagnosis remains challenging for the diseases in the PPA spectrum. These issues in turn present challenges for planning future trials of disease-modifying therapies in PPA: such trials are likely to target specific pathologies and to seek to initiate treatments early in the disease course to minimize cognitive decline
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