Abstract Details

Title Assessing Synaptic Density in Behavioral Variant Frontotemporal Dementia: A Head-to-Head Comparison of 18F-SynVesT-1 and 18F-FDG PET

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P9 - Poster Session 9 (11:45 AM-12:45 PM)

Poster/Presentation
Number 3-019

Objective To assess the distribution patterns and group differences in behavioral variant frontotemporal dementia (bvFTD) patients and healthy controls (HC) using 18F-SynVestT-1 binding, and compare these results with 18F-fluorodeoxyglucose (18F-FDG) in brain regions associated with bvFTD pathology.

Background Synaptic loss is a key pathological process in bvFTD that may drive disease progression. Here, we use in vivo positron emission tomography (PET) imaging with 18F-SynVest-1, a newly developed PET imaging tool from our group that provides quantitative data of synaptic vesicle glycoprotein 2A (SV2A), a marker of synaptic density, to compare with 18F-FDG.

Design/Methods Ten individuals (mean age (SD): 67(10); seven males) with bvFTD and three demographically matched healthy controls (HC; 69(2); three females) participated in both 18F-SynVesT-1 and 18F-FDG scans.Additionally, five controls (58(3); four males) participated in 18F-SynVestT-1 scans only, and thirteen controls (HC; 74 (9); seven males) participated in 18F-FDG scans only for comparison purposes. Binding potential (BPND) and the influx rate constant (Ki) were the primary outcome measures for 18F-SynVesT-1 and 18F-FDG, respectively. The regions of interest were defined using FreeSurfer on MRIs and then applied to PET images. T-tests were used to evaluate between-group differences.Pearson correlations were calculated to investigate associations between synaptic density, glucose metabolism, and bvFTD disease severity.

Results We observed lower synaptic density and glucose metabolism in bvFTD patients compared to HC in the frontal lobe (-30.1%, p<0.01 for 18F-SynVesT-1;-25.9%,p=0.01 for 18F-FDG), insula (-26%, p=0.01; -17.1%,p=0.04), temporal lobe (-26.6%,p=0.01;-18.9%,p=0.03), anterior cingulate cortex (-35.1%, p<0.01;-26.6%,p=0.01), and hippocampus (-30.6%, p<0.01;-18.5%,p=0.05). Higher synaptic density in the frontal cortex was significantly associated with better performance on the Frontal Assessment Battery (r=0.83,p=0.01) and the MoCA (r=0.67,p=0.03). Glucose metabolism was not significantly correlated with cognitive measures in any brain region.

Conclusions These preliminary results suggest that synaptic abnormalities detected by SV2A imaging with 18F-SynVesT-1 PET may outperform the clinical marker 18F-FDG in patients with bvFTD.

Authors/Disclosures
Salih Cayir PRESENTER	Mr. Cayir has nothing to disclose.
Yanghong Yang, MD	Dr. Yang has nothing to disclose.
Waleed N. Ibrahim, MD	Dr. Ibrahim has nothing to disclose.
Mika Naganawa	Mika Naganawa has nothing to disclose.
Jean-Dominique Gallezot	The institution of Jean-Dominique Gallezot has received research support from Intra-cellular Therapies, Inc.. The institution of an immediate family member of Jean-Dominique Gallezot has received research support from Cerevel.
Takuya Toyonaga	No disclosure on file
Nabeel Nabulsi	Nabeel Nabulsi has nothing to disclose.
Yiyun Huang	Yiyun Huang has nothing to disclose.
Richard E Carson	The institution of Richard E Carson has received research support from Cerevel. The institution of Richard E Carson has received research support from Pfizer.
Christopher van Dyck, MD (Yale School of Medicine)	Christopher van Dyck, MD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Christopher van Dyck, MD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono. Christopher van Dyck, MD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cerevel. Christopher van Dyck, MD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eisai. An immediate family member of Christopher van Dyck, MD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Supurnus. An immediate family member of Christopher van Dyck, MD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Polaris Management Partners. The institution of Christopher van Dyck, MD has received research support from Roche/Genentech. The institution of Christopher van Dyck, MD has received research support from Eli Lilly. The institution of Christopher van Dyck, MD has received research support from Biogen. The institution of Christopher van Dyck, MD has received research support from Biohaven. The institution of Christopher van Dyck, MD has received research support from Eisai. The institution of Christopher van Dyck, MD has received research support from UCB. The institution of Christopher van Dyck, MD has received research support from Cerevel. The institution of Christopher van Dyck, MD has received research support from Janssen.
Adam Mecca (Yale School of Medicine)	Adam Mecca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. The institution of Adam Mecca has received research support from NIH. The institution of Adam Mecca has received research support from Eli Lilly. The institution of Adam Mecca has received research support from Genetech. The institution of Adam Mecca has received research support from Janssen.
Arman Fesharaki-Zadeh, MD, PhD (Yale University)	Dr. Fesharaki-Zadeh has nothing to disclose.
David Matuskey, MD (Yale University)	Dr. Matuskey has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Eleisver. The institution of Dr. Matuskey has received research support from Abbvie.

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