Progressive logopenic/phonological aphasia: Erosion of the language network

Abstract

The primary progressive aphasias (PPA) are paradigmatic disorders of language network breakdown associated with focal degeneration of the left cerebral hemisphere. Here we addressed brain correlates of PPA in a detailed neuroanatomical analysis of the third canonical syndrome of PPA, logopenic/phonological aphasia (LPA), in relation to the more widely studied clinico-anatomical syndromes of semantic dementia (SD) and progressive nonfluent aphasia (PNFA). 32 PPA patients (9 SD, 14 PNFA, 9 LPA) and 18 cognitively normal controls had volumetric brain MRI with regional volumetry, cortical thickness, grey and white matter voxel-based morphometry analyses. Five of nine patients with LPA had cerebrospinal fluid biomarkers consistent with Alzheimer (AD) pathology (AD-PPA) and 2/9 patients had progranulin (GRN) mutations (GRN-PPA). The LPA group had tissue loss in a widespread left hemisphere network. Compared with PNFA and SD, the LPA group had more extensive involvement of grey matter in posterior temporal and parietal cortices and long association white matter tracts. Overlapping but distinct networks were involved in the AD-PPA and GRN-PPA subgroups, with more anterior temporal lobe involvement in GRN-PPA. The importance of these findings is threefold: firstly, the clinico-anatomical entity of LPA has a profile of brain damage that is complementary to the network-based disorders of SD and PNFA; secondly, the core phonological processing deficit in LPA is likely to arise from temporo-parietal junction damage but disease spread occurs through the dorsal language network (and in GRN-PPA, also the ventral language network); and finally, GRN mutations provide a specific molecular substrate for language network dysfunction.

Music Perception in Dementia

“…The musical phenotype was more severe in the PNFA group here; the involvement of pitch pattern analysis in this syndrome is in line with previous work [32] and suggests a putative mechanism linking generic mechanisms of dynamic auditory encoding with speech production via the dorsal auditory cortical pathway, extending over a range of timescales relevant to processing of individual and sequential speech sounds [9,77,[90][91][92], Marked involvement of musical perceptual mechanisms might be anticipated from the severe and focal involvement of auditory association areas in the progressive aphasias [9,11]. Although we did not demonstrate a correlation of musical measures with standard measures of verbal encoding, pitch processing mechanisms are likely to be more relevant to prosody (a crucial non-linguistic attribute of speech signals) than phonemic sequencing, at least for non-tonal languages.…”

“…This formulation suggests that music presents the brain with a complex problem of auditory information processing, entailing the decoding of a number of perceptual and cognitive modules [6,7]. On both computational and neuroanatomical grounds, these processes are likely to be vulnerable to the effects of neurodegenerative diseases, most notably AD and primary progressive aphasia syndromes that target peri-Sylvian cortex (progressive nonfluent aphasia (PNFA) and logopenic aphasia (LPA): [8][9][10][11]). A substantial body of structural and functional neuroimaging work in the healthy brain and in patients with focal brain lesions has delineated distributed cortico-subcortical networks that analyze the dimensions of music [6,12,13]: these networks closely overlap the networks targeted in canonical dementia syndromes [14,15].…”

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

“…In contrast, lvPPA showed a diffuse white matter involvement displaying a less stereotyped pattern of progression that not necessarily follows the trajectory of axonal bundles. This divergent pattern of white matter dysfunction mirrors extensive structural imaging and pathological evidence that shows widespread brain atrophy in lvPPA and circumscribed atrophy in svPPA [3,30], and suggests fundamental mechanistic differences in how pathology spreads. Whereas the primary event driving white matter involvement in svPPA is axonal death (i.e., Wallerian degeneration) derived from focal neuronal death [29], the pattern of white matter involvement in lvPPA seems to be different.…”

“…Cognitively, lvPPA, svPPA, and nfvPPA variants are characterized by core language deficits involving repetition, comprehension, and agrammatism, respectively [1]. Structural neuroimaging studies also highlight distinct, primarily left hemispheric, patterns of atrophy in temporal and frontal lobe structures, across PPA variants [1][2][3][4][5][6].…”

“…The impact of this distinction in pathology can be clearly seen in the localization and degree of structural abnormality in lvPPA and svPPA. 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.…”