Primary Progressive Aphasia Lacking Core Features of Nonfluent and Semantic Variants
Watanabe Hiroyuki, Joseph R. Duffy, Heather M. Clark, Mary M. Machulda, Jonathan Graff‐Radford, Nha Trang Thu Pham, Dennis W. Dickson, Val J. Lowe, Jennifer L. Whitwell, Keith A. Josephs
Abstract
BACKGROUND AND OBJECTIVES: Evidence has accumulated that the 2011 consensus criteria for primary progressive aphasia (PPA) do not fully capture features of logopenic variant PPA (lvPPA/LPA). We aimed to examine clinical, neuroimaging, and neuropathologic features of PPA lacking features of nonfluent/semantic variants and to provide practical additions to the 2011 consensus criteria. METHODS: This was a retrospective examination of data from 2 observational cohort studies where patients with PPA were prospectively recruited at Mayo Clinic. 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: F-fluorodeoxyglucose-PET in all groups. Furthermore, repetition-impaired PPA showed severe hypometabolism in the left superior temporal lobe associated with repetition ability. Regarding pathologic diagnoses, 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%). DISCUSSION: 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.