2023 American Academy of Neurology Abstract Website

Rian Bogley¹, Maxime Montembeault⁶, Isabel Allen², Salvatore Spina³, Lea Grinberg⁴, Eric Huang⁵, Joel Kramer³, Katherine Possin³, Katherine Rankin³, Howard Rosen³, Adam Boxer³, Gil Rabinovici³, William Seeley⁴, Virginia Sturm³, David Perry³, Bruce Miller³, Maria Gorno Tempini¹, Zachary Miller¹
¹Memory and Aging Center; Dyslexia Center, ²Biostatistics, ³Memory and Aging Center, ⁴Memory and Aging Center; Pathology, ⁵Pathology, UCSF, ⁶Psychiatry, Douglas Research Centre

Objective:

To investigate the prevalence, demographics, cognitive profiles, and neuropathology of yes/no confusion, a.k.a. aphasic binary reversals (ABR), in primary progressive aphasia (PPA) and frontotemporal lobar degeneration (FTLD) spectrum disorders.

Background:

ABR occurs when patients frequently answer binary choice questions (e.g., yes/no) incorrectly. High rates have been observed in nonfluent PPA (nfvPPA), corticobasal syndrome (CBS), and progressive supranuclear palsy (PSP), diseases often considered as part of a spectrum. To date, no study has thoroughly explored ABR specificity within the broader PPA/FTLD spectrum disorders or deeply examined the cognitive mechanisms behind this phenomenon.

Design/Methods:

Clinical histories across nfvPPA (n=152), CBS (n=106), PSP (n=111), behavioral variant FTD (bvFTD; n=329), logopenic variant PPA (lvPPA; n=213), and semantic variant PPA (svPPA; n=143) were screened for the presence of ABR. Demographics, cognitive measures, and neuropathology were compared between groups with and without ABR.

Results:

ABR prevalence was highest in nfvPPA (43.42%) followed by PSP (16.21%), CBS (13.21%), bvFTD (3.34%), lvPPA (2.81%), and svPPA (0.0%). ABR was highly predictive of nfvPPA diagnosis (OR=25.03 [95% CI: 16.3-38.42]) and the combined nfvPPA/CBS/PSP spectrum (OR=30.06 [95% CI: 17.67-51.12]). Analyses restricted to the nfvPPA/CBS/PSP group revealed no differences in demographics or CDR between those with and without ABR. On cognitive testing, Verbal Agility, Repetition, Digits Forward, Digits Backward, Modified Trails, Semantic Fluency, Phonemic Fluency, Stroop Color Naming and Interference were significantly worse (all p<0.05) in nfvPPA/CBS/PSP with ABR vs. without. On autopsy, 93% (n=38/41) with ABR possessed a sole tauopathy (PSP/CBD/Pick’s/GGT/AGD/unclassifiable tau) vs. 78% (n=85/109) without (Fisher’s Exact, p=0.05; restricting to nfvPPA/CBS cases, 90% [n=27/30] vs. 67% [n=41/61] had sole tauopathy, p=0.02).

Conclusions:

ABR is highly specific to nfvPPA/CBS/PSP spectrum disorders and is associated with worse language and executive function testing and sole tauopathy. Together, the presence of ABR may be capturing pathophysiological differences within these disorders and thus might reflect a novel disease biomarker.