Abstract Details

Title Clinical and Brain Atrophy Components of the Non-Fluent Variant of Primary Progressive Aphasia: etiologic and prognostic implications

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) Behavioral and Cognitive Neurology Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 011

Objective We aimed to determine the clinical and brain atrophy components of the non-fluent variant of primary progressive aphasia (nfvPPA) following a data-driven approach and to explore their value to differentiate pathology subtypes and predict longitudinal decline.

Background nfvPPA is a heterogeneous syndrome associated with multiple neuropathological entities and longitudinal trajectories.

Design/Methods

We recruited 104 participants with nfvPPA and an MRI suitable for analysis at diagnosis. All participants underwent an extensive clinical and neuropsychological assessment. Disease severity was assessed with the FTLD version of the Clinical Dementia Rating sum of boxes (CDR-FTLD-SB). Clinical measures of cognitive impairment (executive function and calculations), speech (dysarthria and apraxia of speech), and language (fluency, syntactic processing, word comprehension, semantic fluency, and repetition) were introduced in principal component analysis. We pre-processed structural MRI with SPM, and combined gray and white matter images to perform multivariate source-based morphometry analysis. Then, we compared the subject-specific scores for clinical and brain atrophy components between pathological diagnoses in 45 participants with autopsy (13 PSP, 16 CBD, 8 Pick's disease, 4 TDP-A, and 4 Other). We studied the longitudinal change of CDR-FTLD-SB with linear mixed-effects models adjusted by age, sex, and baseline CDR-FTLD-SB.

Results Three components accounted for 70% of the variance: (i) "Syntactic-executive" (moderate correlation with CDR-FTLD-SB); (ii) "Apraxia of speech"; and (iii) "Dysarthria". We found five patterns of covarying brain atrophy: (i) "Prefrontal-left" (moderate correaltion with "syntactic-executive" component); (ii) "Premotor" (mild correlation with "dysarthria" component); (iii) "Parieto-temporal-left"; (iv) "Brainstem-cerebellum"; and (v) "Occipital-bilateral". Subject-specific scores on clinical and brain atrophy components did not allow a precise differentiation of specific pathological diagnoses. Subject-specific loadings on "syntactic-executive" component were an independent predictor of faster CDR-FTLD-SB increase during follow-up.

Conclusions The nfvPPA syndrome encompasses a continuum of clinical and brain atrophy components with prognostic implications but suboptimal performance for the identification of specific proteinopathies.

Authors/Disclosures
Ignacio Illan-Gala, Sr., MD, PhD (Hospital de la Santa Creu i Sant Pau) PRESENTER	Dr. Illan-Gala has nothing to disclose.
	No disclosure on file
	No disclosure on file
Sladjana Lukic, PhD (UCSF)	Dr. Lukic has nothing to disclose.
Zachary Miller, MD (UCSF Memory and Aging Center)	Dr. Miller has nothing to disclose.
Neus Falgàs Martínez (UCSF)	Neus Falgàs Martínez has nothing to disclose.
	No disclosure on file
Alberto Lleo, MD (Hospital De La Santa Creu I Sant Pau)	Dr. Lleo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Lleo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. The institution of Dr. Lleo has received research support from Instituto de Salud Carlos III. The institution of Dr. Lleo has received research support from Generalitat de Calalunya (PERIS). The institution of Dr. Lleo has received research support from BBVA Foundation. The institution of Dr. Lleo has received research support from La Caixa Foundation. Dr. Lleo has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
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.
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 Acsel Health. Dr. Spina has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Precision Xtract. 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.
Nina Dronkers, PhD (VA Northern Calif. Health Care System)	The institution of Dr. Dronkers has received research support from NIH. Dr. Dronkers has received personal compensation in the range of $500-$4,999 for serving as a grants reviewer with NIH.
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.
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.
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 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. Dr. Boxer has received research support from Rainwater Charitable Foundation.
	No disclosure on file
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.
	No disclosure on file
Maria Luisa Gorno Tempini, MD, PhD (UCSF Memory and Aging Center)	The institution of Dr. Gorno Tempini has received research support from the NIH.

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