White Matter Disease Correlates with Lexical Retrieval Deficits in Primary Progressive Aphasia

Abstract

Objective: To relate fractional anisotropy (FA) changes associated with the semantic and logopenic variants of primary progressive aphasia (PPA) to measures of lexical retrieval.Methods: We collected neuropsychological testing, volumetric magnetic resonance imaging, and diffusion-weighted imaging on semantic variant PPA (svPPA) (n = 11) and logopenic variant PPA (lvPPA) (n = 13) patients diagnosed using published criteria. We also acquired neuroimaging data on a group of demographically comparable healthy seniors (n = 34). FA was calculated and analyzed using a white matter (WM) tract-specific analysis approach. This approach utilizes anatomically guided data reduction to increase sensitivity and localizes results within canonically defined tracts. We used non-parametric, cluster-based statistical analysis to relate language performance to FA and determine regions of reduced FA in patients.Results: We found widespread FA reductions in WM for both variants of PPA. FA was related to both confrontation naming and category naming fluency performance in left uncinate fasciculus and corpus callosum in svPPA and left superior and inferior longitudinal fasciculi in lvPPA.Conclusion: SvPPA and lvPPA are associated with distinct disruptions of a large-scale network implicated in lexical retrieval, and the WM disease in each phenotype may contribute to language impairments including lexical retrieval.

Classification and clinicoradiologic features of primary progressive aphasia (PPA) and apraxia of speech

“…In keeping with this, there were diffuse white matter abnormalities that were also maximal in the posterior temporal and inferior parietal white matter (Mandelli et al, 2014). The posterior temporal and inferior parietal regions involved in the present study have been linked to phonological loop functions (Gorno-Tempini et al, 2008), and the prominent involvement of the underlying white matter tracts, including the superior and inferior longitudinal fasciculi, likely underlie the poor repetition, naming and comprehension observed in this group (Powers et al, 2013). …”

Prominent microglial activation in cortical white matter is selectively associated with cortical atrophy in primary progressive aphasia

“…For example proton magnetic resonance spectroscopy has demonstrated that abnormalities occur in the arcuate fasciculus in PPA . Diffusion tensor imaging (DTI) studies have linked white matter changes to language impairments specific to the clinical subtypes of PPA . However, the extent to which grey and white matter degeneration occur in parallel or sequentially is not yet known in PPA.…”

Divergent Longitudinal Propagation of White Matter Degradation in Logopenic and Semantic Variants of Primary Progressive Aphasia

“…These tracts have also been identified as being critical components of the language network [12,25,27], in particular speech production and semantic retrieval [27,28]. A recent cross-sectional study dissociated patterns of white matter change in lvPPA and svPPA [11].…”

“…Notably, lvPPA show widespread cortical atrophy to posterior regions of the brain, predominantly affecting the left temporo-parietal junction region, while svPPA show focal change associated with the anterior temporal lobes [2,3]. However, crosssectional studies comparing white matter integrity in lvPPA and svPPA cohorts often fail to show such a distinction [11,12], likely due to wide distributed white matter changes seen in lvPPA.…”