Autopsy Validation of Progressive Supranuclear Palsy‐Predominant Speech/Language Disorder Criteria

Background Progressive supranuclear palsy (PSP) may present as a speech/language disorder (PSP-SL). Objective We assessed pathological correlates of patients with PSP-SL who retained the suggestive of PSP-SL (s.o. PSP-SL) diagnosis versus those who progressed to possible/probable (poss./prob.) PSP. Methods Thirty-four prospectively recruited patient with s.o. PSP-SL completed comprehensive speech/language and neurological assessments longitudinally, died, and underwent autopsy. Results Twelve patients (35%) evolved to poss./prob PSP, while 22 (65%) remained as s.o. PSP-SL. Pathological diagnoses differed across the groups (P = 0.025). Patients with s.o. PSP-SL had four different neuropathologies (corticobasal degeneration [59%], PSP [13%], Pick's disease [14%], and frontotemporal lobar degeneration with TDP-43 [14%]), while all patients with poss./prob. PSP had a 4R-tauopathy (PSP [67%] and corticobasal degeneration [33%]). Development of poss./prob. PSP increased the chance of having PSP pathology by 2.38 times. Conclusions PSP-SL is associated with heterogenous pathologies. Evolution of PSP-SL into poss./prob. PSP is more predictive of underlying PSP pathology than s.o. PSP-SL. © 2021 International Parkinson and Movement Disorder Society.