Abstract Details

Title Clinical and genetic characteristics of patients with very early onset frontotemporal dementia

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S39 - Neurobiology of Dementia (4:42 PM-4:54 PM)

Poster/Presentation
Number 007

Background Frontotemporal dementia may occur in patients who are under 45 years old, often posing a diagnostic challenge, yet little is known about the clinical presentation and underlying genetic causes in this age group.

Objective To describe the clinical and genetic characteristics of patients with very early onset (VEO) frontotemporal dementia (FTD) spectrum disorders.

Design/Methods As part of a prospective study focused on FTD, 780 participants met the research criteria for an FTD spectrum disorder between 2002-2021. Of these, 40 patients (5.1%, 18 females) presented with age at onset < 45 years and constituted the VEO-FTD group. Their research records were reviewed to delineate their clinical characteristics. A panel of 40 dementia and amyotrophic lateral sclerosis-associated genes was screened for pathogenic genetic variation using standardized methods.

Results

Behavioral variant of frontotemporal dementia was disproportionally represented in the VEO-FTD group (n = 35, 87.5%) suggesting selective vulnerability of the social-emotional brain networks to frontotemporal lobar degeneration underlying neuropathologies in this age range. The median age at first symptom was 39 (interquartile range (IQR) = 32-42.2) years, and the median diagnostic delay from symptom onset was 4 (IQR 2-8.25) years. Initial misdiagnosis with a primary psychiatric disorder was prevalent, occurring in 17 (42.3%) of patients, and was diverse including mood, psychotic, anxiety, and addictive disorders. In five patients (12.5%), positive psychotic symptoms were reported, mostly as a presenting symptom or arising within a year from the first symptom. Among the VEO-FTD patients, 18 (45%) carried C9orf72, MAPT or UBQLN2 pathogenic variants.

Conclusions

FTD spectrum disorders may occur under the age of 45 and are often misdiagnosed. The high prevalence of monogenic causes in this age group warrants timely genetic testing, especially in the era of emerging gene-specific therapies.

Authors/Disclosures
Adit Friedberg, MD (UCSF) PRESENTER	The institution of Dr. Friedberg has received research support from The Larry L. Hillblom Foundation . The institution of Dr. Friedberg has received research support from The Global Brain Health Institute.
	No disclosure on file
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Daniel H. Geschwind, MD, PhD (UCLA)	Dr. Geschwind has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Ovid Therapeutics, Inc.. Dr. Geschwind has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for AcuraStem, Inc.. Dr. Geschwind has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Axial Biotherapeutics, Inc.. Dr. Geschwind has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Falcon Computing. Dr. Geschwind 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 Elsevier-Biological Psychiatry. Dr. Geschwind has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for NYAS. Dr. Geschwind has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for Covington& Burling LLP. Dr. Geschwind has stock in none related to talk. The institution of Dr. Geschwind has received research support from CurePSP. The institution of Dr. Geschwind has received research support from NINDS. The institution of Dr. Geschwind has received research support from Rainwater Charitable Foundation. The institution of Dr. Geschwind has received research support from NIMH. The institution of Dr. Geschwind has received research support from NINDS. The institution of Dr. Geschwind has received research support from NIH. The institution of Dr. Geschwind has received research support from The Simons Foundation. The institution of Dr. Geschwind has received research support from NIH/NIMH. The institution of Dr. Geschwind has received research support from Adelson Medical Research Foundation. The institution of Dr. Geschwind has received research support from NINDS. The institution of Dr. Geschwind has received research support from NIMH. The institution of Dr. Geschwind has received research support from NINDS/NIA. The institution of Dr. Geschwind has received research support from NIH/NIMH. The institution of Dr. Geschwind has received research support from Adelson Medical Research Foundation. The institution of Dr. Geschwind has received research support from NIH/NINDS. The institution of Dr. Geschwind has received research support from NIH/NIMH. The institution of Dr. Geschwind has received research support from NIH/NIMH. The institution of Dr. Geschwind has received research support from Adelson Medical Research Foundation. The institution of Dr. Geschwind has received research support from U of Virginia and NIH/NIMH. The institution of Dr. Geschwind has received research support from NIH. The institution of Dr. Geschwind has received research support from NIH/NHGRI. The institution of Dr. Geschwind has received research support from NIH/NIMH. Dr. Geschwind has received intellectual property interests from a discovery or technology relating to health care. Dr. Geschwind has received intellectual property interests from a discovery or technology relating to health care. Dr. Geschwind has received intellectual property interests from a discovery or technology relating to health care. Dr. Geschwind has received intellectual property interests from a discovery or technology relating to health care.
William 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.
Jennifer S. Yokoyama, PhD (UCSF, Memory and Aging Center)	The institution of Dr. Yokoyama has received research support from NIH. The institution of Dr. Yokoyama has received research support from Alzheimer's Association . The institution of Dr. Yokoyama has received research support from Mary Oakley Foundation. The institution of Dr. Yokoyama has received research support from Alector. The institution of Dr. Yokoyama has received research support from Transposon. The institution of Dr. Yokoyama has received research support from Rainwater Charitable Foundation.
Bruce L. Miller, MD, FAAN (University of California, San Francisco)	Dr. Miller has nothing to disclose.