Clinical, Anatomical, and Pathological Features in the Three Variants of Primary Progressive Aphasia: A Review

Abstract

Primary progressive aphasias (PPA) are neurodegenerative diseases clinically characterized by an early and relatively isolated language impairment. Three main clinical variants, namely the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA) have been described, each with specific linguistic/cognitive deficits, corresponding anatomical and most probable pathological features. Since the discovery and the development of diagnostic criteria for the PPA variants by the experts in the field, significant progress has been made in the understanding of these diseases. This review aims to provide an overview of the literature on each of the PPA variant in terms of their clinical, anatomical and pathological features, with a specific focus on recent findings. In terms of clinical advancements, recent studies have allowed a better characterization and differentiation of PPA patients based on both their linguistic and non-linguistic profiles. In terms of neuroimaging, techniques such as diffusion imaging and resting-state fMRI have allowed a deeper understanding of the impact of PPA on structural and functional connectivity alterations beyond the well-defined pattern of regional gray matter atrophy. Finally, in terms of pathology, despite significant advances, clinico-pathological correspondence in PPA remains far from absolute. Nonetheless, the improved characterization of PPA has the potential to have a positive impact on the management of patients. Improved reliability of diagnoses and the development of reliable in vivo biomarkers for underlying neuropathology will also be increasingly important in the future as trials for etiology-specific treatments become available.

Globular Glial Tauopathy Type I Presenting as Atypical Progressive Aphasia, With Comorbid Limbic-Predominant Age-Related TDP-43 Encephalopathy

“…This finding, in line with reported white matter lesion in the GGT type I, struck the dorsal language stream and could have had a severe impact on syntax deficits and frontal inhibition late in the disease course. Moreover, in nfvPPA cases (with similar findings to ours), tauopathy-related parkinsonism and supranuclear gaze palsy are often reported (Rohrer et al, 2010;Montembeault et al, 2018).…”

Primary progressive aphasia: misdiagnosis with ‘normal imaging’

“…Although there are some controversies, three clinical variants of primary progressive aphasia (PPA) are generally recognised: the non‐fluent/agrammatic variant (nfvPPA or avPPA), in which there may or may not also be an apraxia of speech (AOS); the semantic variant (svPPA), and the logopenic variant (lvPPA) 1,2 . While nfvPPA and svPPA are characterised as linguistic variants of frontotemporal dementia (FTD), 3 lvPPA is most often associated with Alzheimer‐type pathology and is therefore classified with Alzheimer's disease (AD) 4 .…”

Ethical and Practical Challenges of the Communication and Behavioral Manifestations of Primary Progressive Aphasia

“…This neurodegenerative disease is defined by the insidious onset, gradual decline, and predominance of language impairments (in contrast to memory impairment as seen in Alzheimer's disease [AD]) and compromised participation in activities of daily living due to these deficits. 1,2 Three different PPA variants are specified by international consensus criteria based on clinical presentation (language manifestations), patterns of atrophy, and/or underlying neuropathology: logopenic variant PPA (lvPPA), nonfluent agrammatic PPA (nfaPPA), and semantic variant PPA (svPPA) 3 (Table 1). Individuals with lvPPA are distinguished from other variants by impaired single-word retrieval in spontaneous speech and naming, impaired repetition of phrases and sentences, 4 and left temporoparietal atrophy.…”