A wealth of neuroimaging research has associated semantic variant primary progressive aphasia with distributed cortical atrophy that is most prominent in the left anterior temporal cortex; however, there is little consensus regarding which region within the anterior temporal cortex is most prominently damaged, which may indicate the putative origin of neurodegeneration. In this study, we localized the most prominent and consistent region of atrophy in semantic variant primary progressive aphasia using cortical thickness analysis in two independent patient samples (n = 16 and 28, respectively) relative to age-matched controls (n = 30). Across both samples the point of maximal atrophy was located in the same region of the left temporal pole. This same region was the point of maximal atrophy in 100% of individual patients in both semantic variant primary progressive aphasia samples. Using resting state functional connectivity in healthy young adults (n = 89), we showed that the seed region derived from the semantic variant primary progressive aphasia analysis was strongly connected with a large-scale network that closely resembled the distributed atrophy pattern in semantic variant primary progressive aphasia. In both patient samples, the magnitude of atrophy within a brain region was predicted by that region's strength of functional connectivity to the temporopolar seed region in healthy adults. These findings suggest that cortical atrophy in semantic variant primary progressive aphasia may follow connectional pathways within a large-scale network that converges on the temporal pole.

“Functional communication” refers to an individual’s ability to communicate effectively in his or her everyday environment, and thus is a paramount skill to monitor and target therapeutically in people with aphasia. However, traditional controlled-paradigm assessments commonly used in both research and clinical settings often fail to adequately capture this ability. In the current study, facets of functional communication were measured from picture-elicited speech samples from 70 individuals with mild primary progressive aphasia (PPA), including the three variants, and 31 age-matched controls. Building upon methods recently used by Berube et al. (2019), we measured the informativeness of speech by quantifying the content of each patient’s description that was relevant to a picture relative to the total amount of speech they produced. Importantly, form-based errors, such as mispronunciations of words, unusual word choices, or grammatical mistakes are not penalized in this approach. We found that the relative informativeness, or efficiency, of speech was preserved in non-fluent variant PPA patients as compared with controls, whereas the logopenic and semantic variant PPA patients produced significantly less informative output. Furthermore, reduced informativeness in the semantic variant is attributable to a lower production of content units and a propensity for self-referential tangents, whereas for the logopenic variant, a lower production of content units and relatively ”empty” speech and false starts contribute to this reduction. These findings demonstrate that functional communication impairment does not uniformly affect all the PPA variants and highlight the utility of naturalistic speech analysis for measuring the breakdown of functional communication in PPA.

Despite the important role of written language in everyday life, abnormalities in functional written communication have been sparsely investigated in Primary Progressive Aphasia (PPA). Prior studies have analyzed written language separately in the three variants of PPA - nonfluent (nfvPPA), logopenic (lvPPA), and semantic (svPPA) - but have rarely compared them to each other or to spoken language. Manual analysis of written language can be a time-consuming process. We developed a program which uses a language parser and quantifies content units (CU) and total units (U) in written language samples. The program was used to analyze written and spoken descriptions of the WAB Picnic scene, based on a pre-defined CU corpus. We then calculated the ratio of CU to U (CU/U Ratio) as a measure of content density. Our cohort included 115 participants (20 control participants for written, 20 control participants for spoken, 28 participants with nfvPPA, 30 with lvPPA, and 17 with svPPA). We compared written language between patients with PPA and control participants and written to spoken language in patients with the three variants of PPA. Finally, we analyzed CU and U in relation to the Progressive Aphasia Severity Scale Sum of Boxes and the Clinical Dementia Rating Sum of Boxes. Our program identified CU with a validity of 99.7% (95%CI 99.5 to 99.8) compared to manual annotation of the samples. All patients with PPA wrote fewer total units than controls (p<0.001). Patients with lvPPA (p=0.013) and svPPA (0.004) wrote fewer CU than controls. The CU/U Ratio was higher in nfvPPA and svPPA than controls (p=0.019 in both cases), but no different between lvPPA patients and controls (p=0.962). Participants with lvPPA (p<0.001) and svPPA (p=0.04) produced fewer CU in written samples compared to spoken. A two-way ANOVA showed all groups produced fewer units in written samples compared to spoken (p<0.001). However, the decrease in written CU compared to spoken was smaller than the decrease in written units compared to spoken in participants with PPA, resulting in a larger written CU/U Ratio when compared to spoken language (p<0.001). nfvPPA patients produced correlated written and spoken CU (R=0.5, p=0.009) and total units (R=0.64, p<0.001), but this was not the case for lvPPA or svPPA. Considering all PPA patients, fewer CU were produced in those with greater aphasia severity (PASS SoB, R=-0.24, p=0.04) and dementia severity (CDR SoB, R=-0.34, p=0.004). In conclusion, we observed reduced written content in patients with PPA compared to controls, with a preference for content over non-content units in patients with nfvPPA and svPPA. When comparing written to spoken language, we observed a similar "telegraphic" style in both modalities in patients with nfvPPA, which was different from patients with svPPA and lvPPA, who use significantly less non-content units in writing than in speech. Lastly, we show how our program provides a time-efficient tool, which could enable feedback and tracking of writing as an important feature of language and cognition.