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We report a patient with logopenic variant primary progressive aphasia (lv-PPA) who was diagnosed as having non-Alzheimer's disease (AD) tauopathy after multiple biophysical/biological examinations, including amyloid and 18F-florzolotau tau positron emission tomography (PET), had been performed. A woman in her late 60s who had previously been diagnosed as having AD was referred to us for a further, detailed examination. She had been unaware of any symptoms at the time of AD diagnosis, but she subsequently became gradually aware of a speech impairment. She talked nearly completely and fluently, although she occasionally exhibited word-finding difficulty and made phonological errors during naming, word fluency testing, and sentence repetition; these findings met the criteria for the diagnosis of lv-PPA, which is known to be observed more commonly in AD than in other proteinopathies. Magnetic resonance imaging, single photon emission computed tomography, and plasma phosphorylated tau and plasma neurofilament light chain measurements showed an AD-like pattern. However, both 11C-Pittsburgh compound-B and 18F-florbetaben amyloid PET showed negative results, whereas 18F-florzolotau tau PET yielded positive results, with radio signals predominantly in the left superior temporal gyrus, middle temporal gyrus, supramarginal gyrus, and frontal operculum. Whole-genome sequencing revealed no known dominantly inherited mutations in AD or frontotemporal lobar degeneration genes, including the genes encoding amyloid precursor protein, microtubule-associated protein tau, presenilin 1 and 2. To the best of our knowledge, this patient was a rare case of lv-PPA who was diagnosed as having non-AD tauopathy based on the results of multiple examinations, including whole-genome sequencing, plasma measurement, and amyloid and 18F-florzolotau tau PET. This case underscores the clinicopathologically heterogeneous nature of this syndrome. [ABSTRACT FROM AUTHOR]

Logopenic variant primary progressive aphasia (lvPPA) is a neurodegenerative language disorder primarily characterized by impaired phonological processing. Sentence repetition and comprehension deficits are observed in lvPPA and linked to impaired phonological working memory, but recent evidence also implicates impaired speech perception. Currently, neural encoding of the speech envelope, which forms the scaffolding for perception, is not clearly understood in lvPPA. We leveraged recent analytical advances in electrophysiology to examine speech envelope encoding in lvPPA. We assessed cortical tracking of the speech envelope and in-task comprehension of two spoken narratives in individuals with lvPPA (n = 10) and age-matched (n = 10) controls. Despite markedly reduced narrative comprehension relative to controls, individuals with lvPPA had increased cortical tracking of the speech envelope in theta oscillations, which track low-level features (e.g., syllables), but not delta oscillations, which track speech units that unfold across a longer time scale (e.g., words, phrases, prosody). This neural signature was highly correlated across narratives. Results indicate an increased reliance on acoustic cues during speech encoding. This may reflect inefficient encoding of bottom-up speech cues, likely as a consequence of dysfunctional temporoparietal cortex.

Logopenic variant primary progressive aphasia (lvPPA) is a neurodegenerative language disorder primarily characterized by impaired phonological processing. Sentence repetition and comprehension deficits are observed in lvPPA and linked to impaired phonological working memory, but recent evidence also implicates impaired speech perception. Currently, neural encoding of the speech envelope, which forms the scaffolding for perception, is not clearly understood in lvPPA. We leveraged recent analytical advances in electrophysiology to examine speech envelope encoding in lvPPA. We assessed cortical tracking of the speech envelope and in-task comprehension of two spoken narratives in individuals with lvPPA (n = 10) and age-matched (n = 10) controls. Despite markedly reduced narrative comprehension relative to controls, individuals with lvPPA had increased cortical tracking of the speech envelope in theta oscillations, which track low-level features (e.g., syllables), but not delta oscillations, which track speech units that unfold across a longer time scale (e.g., words, phrases, prosody). This neural signature was highly correlated across narratives. Results indicate an increased reliance on acoustic cues during speech encoding. This may reflect inefficient encoding of bottom-up speech cues, likely as a consequence of dysfunctional temporoparietal cortex. [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]