Abstract Details

Title Getting Granular with Progranulin: Abnormal Eating in FTLD+GRN

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-004

Objective To deeply clinically phenotype progranulin-associated frontotemporal lobar degeneration (FTLD+GRN) and compare to sporadic FTLD with identical TDP-43 pathology (FTLD-GRN).

Background GRN encodes progranulin, a growth factor implicated in myriad processes, and deleterious mutations resulting in haploinsufficiency of GRN cause FTLD-TDP. While this mutation may affect the entire cerebrum, we sought to determine whether FTLD-related clinical features are more prevalent or severe in FTLD+GRN than in sporadic cases with identical FTLD-TDP pathology, suggesting a different locus of TDP-43 pathology in mutation carriers.

Design/Methods A retrospective cohort design was utilized. Inclusion criteria were either FTD-spectrum disorder due to GRN mutation (FTLD+GRN=30) or autopsy-confirmed FTLD-TDP with identical subtype A/B pathology but no FTLD-associated mutation (FTLD-GRN=28). Presence/absence of behavioral symptoms and cognitive/motor signs were extracted from records with standardized templates blinded to GRN status. Frequencies of symptoms/signs were compared using chi-square analyses.

Results FTLD+GRN and FTLD-GRN had similar mean age at onset (FTLD+GRN=59.4, 95%CI 56.6-62.1; FTLD-GRN= 60.6, 95%CI 56.4-64.8) and overall survival (FTLD+GRN=6.8, 95%CI 5.4-8.1, n=24; FTLD-GRN =7.0, 95%CI 5.3-8.7, n=28). While abnormal eating was pervasive (FTLD+GRN=66.7% and FTLD-GRN= 51.9%, p=0.268), hyperorality was more severe in FTLD+GRN: advanced hyperoral behavior of pica was more common in FTLD+GRN and absent in FTLD-GRN (13.3% vs 0%, p<0.05). Thus, we also examined severity of hyperorality using a measure adapted from a previously-published DAPHNE scale (0=none; 1=carbohydrate craving or increased eating/drinking/smoking; 2=gorging/weight-gain/food-fads; 3=pica/non-repressible food-foraging) and found 20% of FTLD+GRN had hyperorality ordinal scores of 3 (severe) vs 0% for FTLD-GRN (p<0.012). Simple motor stereotypies were more prevalent in FTLD+GRN (42.9% vs 11.5%, p=0.010), as was visuospatial dysfunction (56% vs 28%, p=0.045).

Conclusions

FTLD+GRN patients had more severe hyperorality and simple motor stereotypies than FTLD-GRN, suggesting greater susceptibility of behavioral networks that are centered in ventral and medial frontal regions in GRN mutation carriers compared to sporadic FTLD-TDP.

Authors/Disclosures
Lauren McCollum, MD (Pat Summitt Clinic) PRESENTER	No disclosure on file
	No disclosure on file
Michael Baer, MD (University of Pennsylvania)	Dr. Baer has nothing to disclose.
	No disclosure on file
David A. Wolk, MD, FAAN (University of Pennsylvania)	Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Functional Neuromodulation. Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GSK. The institution of Dr. Wolk has received research support from Biogen. Dr. Wolk has received publishing royalties from a publication relating to health care. Dr. Wolk has received personal compensation in the range of $5,000-$9,999 for serving as a CME speaker with Eli Lilly.
John Q. Trojanowski, MD, PhD (University of PA School of Med)	Dr. Trojanowski has nothing to disclose.
Murray Grossman, MD, FAAN (University of Pennsylvania)	Dr. Grossman has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology. The institution of Dr. Grossman has received research support from NIH.
David Irwin, MD (University of Pennsylvania)	The institution of Dr. Irwin has received research support from NIH. The institution of Dr. Irwin has received research support from Prevail. The institution of Dr. Irwin has received research support from Passage Bio. The institution of Dr. Irwin has received research support from Alector. The institution of Dr. Irwin has received research support from Transposon. The institution of Dr. Irwin has received research support from Denali. The institution of Dr. Irwin has received research support from Cervo Med.

��ɫ��

��ɫ��