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Abstract Details

Aphasic Binary Reversals as a Novel Biomarker Across Dementia Syndromes
Aging, Dementia, and Behavioral Neurology
P6 - Poster Session 6 (5:30 PM-6:30 PM)
7-010

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.
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.
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.

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).

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.
Authors/Disclosures
Rian L. Bogley (UCSF)
PRESENTER 		Mr. Bogley has nothing to disclose.
Maxime Montembeault, PhD (UCSF Memory and Aging Center) Dr. Montembeault has nothing to disclose.
No disclosure on file
Salvatore Spina, MD (UCSF Memory and Aging Center) Dr. Spina has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Techspert.io. Dr. Spina has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lumanity. Dr. Spina has received research support from Tau Consortium. Dr. Spina has received research support from Chan Zuckerberg Initiative, LLC. Dr. Spina has received research support from Bluefield Project to Cure FTD. Dr. Spina has received research support from NIH. Dr. Spina has received research support from Larry L. Hillblom Foundation. Dr. Spina has received personal compensation in the range of $500-$4,999 for serving as a Invited Speaker with Peking Union Medical Center Hospital.
Lea Grinberg Lea Grinberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Curasen Inc. The institution of Lea Grinberg has received research support from NIH. The institution of Lea Grinberg has received research support from Eli Lilly. The institution of Lea Grinberg has received research support from BrightFouus. The institution of Lea Grinberg has received research support from Rainwater Charity Foundation.
No disclosure on file
Joel Kramer, PhD (UCSF Medical Center) The institution of Dr. Kramer has received research support from tau consortium. Dr. Kramer has received publishing royalties from a publication relating to health care.
Katherine L. Possin, PhD (U of CA San Francisco, Neurology) Dr. Possin has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for ClearView Healthcare Partners. The institution of Dr. Possin has received research support from Quest Diagnostics. The institution of Dr. Possin has received research support from NIH. The institution of Dr. Possin has received research support from The Global Brain Health Institute. The institution of Dr. Possin has received research support from The Rainwater Foundation.
Katherine P. Rankin, PhD (University of California San Francisco) The institution of Dr. Rankin has received research support from Marcus Foundation.
Howard J. Rosen, MD (UCSF) Dr. Rosen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly . Dr. Rosen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alector. The institution of Dr. Rosen has received research support from NIH. The institution of Dr. Rosen has received research support from State of CA. Dr. Rosen has a non-compensated relationship as a Consultant with Prevail Therapeutics that is relevant to AAN interests or activities. Dr. Rosen has a non-compensated relationship as a consultant with Alchemab that is relevant to AAN interests or activities.
Adam L. Boxer, MD, PhD (University of California, San Francisco) An immediate family member of Dr. Boxer has received personal compensation for serving as an employee of Kaiser Permanente. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono. Dr. Boxer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Oscotec. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arrowhead. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurocrine Biosciences. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Switch. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arvinas. Dr. Boxer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alector. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Transposon. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen . Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Boxer has stock in Alector. Dr. Boxer has stock in Arvinas. Dr. Boxer has stock in Neurovanda. The institution of Dr. Boxer has received research support from Biogen. The institution of Dr. Boxer has received research support from Eisai. The institution of Dr. Boxer has received research support from Regeneron. The institution of Dr. Boxer has received research support from NIH. The institution of Dr. Boxer has received research support from Bluefield Project-5. Dr. Boxer has received research support from Rainwater Charitable Foundation. Dr. Boxer has received research support from GHR Foundation. Dr. Boxer has received intellectual property interests from a discovery or technology relating to health care.
Gil D. Rabinovici, MD, FAAN (UCSF Memory & Aging Center) Dr. Rabinovici has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alector. Dr. Rabinovici has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Norodisk. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for C2N. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Johnson & Joihnson. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Peerview. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medscape. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA. The institution of Dr. Rabinovici has received research support from NIH. The institution of Dr. Rabinovici has received research support from American College of Radiology. The institution of Dr. Rabinovici has received research support from Alzheimer's Association. The institution of Dr. Rabinovici has received research support from Rainwater Charitable Foundation. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Topic Chair, Course Director and teacher with AAN. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Grant reviewer with NIH. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Invited speaker with ANA.
William W. Seeley, MD Dr. Seeley has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GLG Council. Dr. Seeley has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint Global Consulting. Dr. Seeley has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BridgeBio. Dr. Seeley has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Seeley has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lyterian Therapeutics. The institution of Dr. Seeley has received research support from NIH. The institution of Dr. Seeley has received research support from Rainwater Charitable Foundation. The institution of Dr. Seeley has received research support from Bluefield Project to Cure FTD. The institution of Dr. Seeley has received research support from Chan-Zuckerberg Initiative.
Virginia Sturm, PhD Dr. Sturm has nothing to disclose.
David Perry, MD The institution of Dr. Perry has received research support from NIH/NIA.
Bruce L. Miller, MD, FAAN (University of California, San Francisco) Dr. Miller has nothing to disclose.
Maria Luisa Gorno Tempini, MD, PhD (UCSF Memory and Aging Center) The institution of Dr. Gorno Tempini has received research support from the NIH.
Zachary Miller, MD (UCSF Memory and Aging Center) Dr. Miller has nothing to disclose.