Heterogeneity within primary progressive aphasia (PPA): differences between variants in functional communication, and a new sub-variant of logopenic variant PPA

Abstract

Primary progressive aphasia (PPA) is an acquired neurodegenerative syndrome that has specific and devastating effects on an individual’s speech and language ability. Based on a detailed assessment of behavior and cognition, combined with structural neuroimaging data and pathological evidence, PPA is typically classified into three variants: the non-fluent (nfvPPA), semantic (svPPA), and logopenic (lvPPA). However, in spite of some distinct behavioral features, i) PPA individuals exhibit some shared features, including an impairment in lexical retrieval (anomia), and more generally, ii) researchers have long acknowledged the heterogeneity within each variant. Here, I tackle two important issues in PPA research. First, inspired by a recent shift towards naturalistic paradigms in the field of language, I use naturalistic speech samples to examine ‘functional communication’ in the three variants of PPA – an ability most relevant to everyday functioning and often not captured by traditional controlled-paradigm assessments. Second, I examine the variability within lvPPA and identify a new sub-variant. In Study 1, I compare individuals in the mild stages of PPA from each of the three variants to age-matched control participants with respect to their lexical production abilities on a picture description task. Using a measure recently introduced by Berube et al. (2019), I show that individuals with nfvPPA, despite grammatical impairment, exhibit preserved informativeness whereas lvPPA and svPPA do not. Furthermore, I show that the reduction in informativeness in svPPA is due to a propensity for self-referential tangents. In Study 2, using a diverse set of functional language assessments, I identify a distinct profile of lvPPA with atypical Wernicke’s-like symptoms (WlvPPA): fluent speech and impaired auditory comprehension. Finally, Study 3 extends these behavioral findings by determining potential neural underpinnings of this distinct sub-variant through a longitudinal structural anatomical investigation of one of these patients. The results suggest that WlvPPA may arise from additional atrophy in regions outside of what is traditionally considered the language network. These results i) highlight the importance of supplementing standardized language batteries with assessments of functional communication using naturalistic speech samples, and ii) demonstrate that heterogeneity in PPA may manifest as qualitatively distinct functional profiles.