Clinical, Neuroimaging, and Neuropathologic Features of Primary Progressive Aphasia Lacking Core Features of Nonfluent and Semantic Variants
Hiroyuki Watanabe1, Joseph Duffy1, Heather Clark1, Mary Machulda2, Jonathan Graff-Radford1, Nha Trang Thu Pham3, Dennis Dickson4, Val Lowe3, Jennifer Whitwell3, Keith Josephs1
1Neurology, 2Psychology, 3Radiology, 4Neuroscience, Mayo Clinic
Objective:
To examine clinical, neuroimaging, and neuropathologic features of primary progressive aphasia (PPA) lacking features of nonfluent/semantic variants and to provide practical additions to the 2011 consensus criteria for PPA.
Background:
Evidence has accumulated that the 2011 consensus criteria do not fully capture features of logopenic variant PPA (lvPPA/LPA).
Design/Methods:
This was a retrospective examination of data from 2 observational cohort studies where patients with PPA were prospectively recruited. Based on performance on 2 cardinal features (repetition and comprehension), patients were classified as: pure-LPA (poor repetition, acceptable comprehension), Wernicke-like (poor in both), anomic-like (acceptable in both), and transcortical sensory aphasia–like (TCSA-like) (acceptable repetition, poor comprehension).
Results:
The entire cohort consisted of 102 patients with PPA lacking features of nonfluent/semantic variants. The proportion of repetition-preserved PPA (anomic-like and TCSA-like) was more than double that of repetition-impaired PPA (pure-LPA and Wernicke-like) (73% vs 27%). Regarding clinical course (n=31), the anomic-like subgroup was a prodromal state of the pure-LPA or TCSA-like subgroup, whereas the pure-LPA and TCSA-like subgroups were a prodromal state of the Wernicke-like subgroup. There was left temporoparietal atrophy on MRI and/or hypometabolism on 18F-fluorodeoxyglucose-PET in all groups. Regarding pathologic diagnoses (n=23), 70% had Alzheimer disease (AD). The pure-LPA, Wernicke-like, and TCSA-like subgroups all showed AD pathology. Only 53% of the anomic-like subgroup had AD. The remaining 47% showed Pick disease (7%), frontotemporal lobar degeneration with TDP-43–immunoreactive pathology (20%), and Lewy body disease (20%).
Conclusions:
This observed clinical heterogeneity reflects different time points/severities of the same disease process and hence can be reconceptualized as an AD-related aphasia spectrum, incorporating lvPPA and the 4 subgroups (pure-LPA, Wernicke-like, anomic-like, and TCSA-like). Specifying moderate/severe repetition deficits as a core feature of lvPPA in the 2011 consensus criteria can enhance its pathologic correlations. Recognizing progressive anomic aphasia (anomic-like) as an additional PPA variant could lessen pathologic heterogeneity of lvPPA.
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