In Vivo Correlates of Pathological Diagnosis in Primary Progressive Aphasia (P4.009)

Objective: To investigate the relationship between in vivo clinical and neuroimaging features and neuropathologic findings in a large cohort of patients with primary progressive aphasia (PPA). Background:Nonfluent/agrammatic (nfvPPA) and semantic (svPPA) variants of PPA are most often encompassed by the spectrum of frontotemporal lobar degeneration (FTLD), whereas Alzheimer’s disease (AD) pathology has been shown in most cases of logopenic variant PPA (lvPPA). Clinical and neuroanatomical heterogeneity within each variant might be due to specific pathologic correlates. Large clinicopathological series of prospectively evaluated PPA patients are still lacking. Methods: We evaluated clinical, MRI and neuropathologic data from 59 patients with sporadic PPA, namely 25 nfvPPA, 24 svPPA, 7 lvPPA and 3 patients not meeting criteria for any specific variant (mixedPPA). Patterns of grey matter (GM) and white matter (WM) atrophy at presentation were assessed in each clinical and pathologic subgroup. Results: We identified prevalent underlying pathology for each PPA variant, as 18/25 (72[percnt]) nfvPPA patients were diagnosed with 4R-tau FTLD (specifically, 11 CBD and 7 PSP), 19/24 (79[percnt]) svPPA showed TDP-C FTLD, and all lvPPA had AD pathology. Other pathological diagnoses were: Pick’s disease (PiD), observed in 4 nfvPPA, 2 svPPA and 2 mixedPPA; TDP-A FTLD (2 nfvPPA); TDP-B FTLD (2 svPPA); AD (1 nfvPPA and 1 mixedPPA); and WM 4R-tauopathy with globular glial inclusions (1 svPPA). PiD was associated with severe, early neuropsychiatric symptoms and extensive atrophy involving mainly left but also right frontal and temporal lobes, across all clinical variants. NfvPPA-TDP showed selective left posterior frontal GM atrophy. SvPPA-tau had severe medial temporal and orbitofrontal GM and WM atrophy and greater executive impairment than svPPA-TDP. Conclusions: Patterns of GM and WM atrophy may suggest atypical pathologic diagnosis within each PPA variant in vivo. PiD is associated with distinctive behavioral alterations and may underlie different profiles of language impairment.