Abstract Details

Title Functional Connectivity Rearrangements Propagating from Disease Epicenters in Frontotemporal Lobar Degeneration Variants

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P12 - Poster Session 12 (5:30 PM-6:30 PM)

Poster/Presentation
Number 3-001

Background Although FTLD clinical presentations share a damage of frontal and temporal lobes, there is an obvious divergence in the vulnerability of brain networks, leading to heterogeneous symptoms accompanying the behavioral variant of frontotemporal dementia (bvFTD) and the nonfluent (nfvPPA) and semantic variants of primary progressive aphasia (svPPA). SFC analysis is a graph-theory-based neuroimaging method that detects whole-brain functional couplings of a selected region of interest, at increasing link-step distances.

Objective To explore stepwise functional connectivity (SFC) rearrangements in patients affected by frontotemporal lobar degeneration (FTLD) variants.

Design/Methods Patients with bvFTD (n=26), nfvPPA (n=11) or svPPA (n=14) underwent clinical evaluation and 3T MRI scan. For each subgroup, cortical thickness was assessed, in order to identify the peak of atrophy (considered as the disease epicenter), when compared with 37 age- and sex-matched healthy controls. These areas were used as seed regions for the subsequent SFC analyses.

Results The selected seed regions were the right orbitofrontal cortex for bvFTD, left supplementary motor area for nfvPPA, and left temporal pole for svPPA. Compared with controls, all three patient groups showed decreased SFC in widespread regions with direct/intermediate connections with the respective seed regions. bvFTD and nfvPPA patients also showed increased SFC within the brain regions closest to the respective seed region and homologous contralateral cortices at one link-step. At further link-steps, SFC increase was also observed in the posterior cerebellum of bvFTD and nfvPPA patients, and the superior frontal cortex of svPPA patients.

Conclusions Our findings indicate an increase in the short-range direct connectivity around the disease epicenters of FTLD, probably as a compensation for neurodegeneration, in contrast with widespread functional rearrangements that characterize each phenotype across different link-steps. This was the first study exploring SFC in FTLD, opening promising perspectives to understand the physiopathological underpinnings of these presentations and model disease evolution.

Authors/Disclosures
Edoardo G. Spinelli, MD PRESENTER	Dr. Spinelli has nothing to disclose.
	No disclosure on file
Silvia Basaia	Silvia Basaia has nothing to disclose.
Camilla Cividini, MSc (San Raffaele Scientific Institute, Vita-Salute San Raffaele University)	Ms. Cividini has nothing to disclose.
	No disclosure on file
Elisa Canu (Ospedale San Raffaele)	The institution of Elisa Canu has received research support from Italian Ministry of Health .
Veronica Castelnovo, MSc (San Raffaele Scientific Institute, Vita-Salute San Raffaele University)	Dr. Castelnovo has nothing to disclose.
Giuseppe Magnani	Giuseppe Magnani has nothing to disclose.
Francesca Caso, MD (Universita' Vita Salute San Raffaele)	Dr. Caso has nothing to disclose.
Paola Caroppo	No disclosure on file
Sara Prioni (Fondazione IRCCS Istituto Neurologico Carlo Besta)	No disclosure on file
	No disclosure on file
Lucio Tremolizzo (UNIMIB)	No disclosure on file
Ildebrando H. Appollonio, MD (Neurology Section, Dept. of Medicine and Surgery, University of Milano Bicocca)	Dr. Appollonio has nothing to disclose.
Vincenzo Silani, MD, FAAN (University of Milan Medical School - IRCCS Istituto Auxologico Italiano)	Dr. Silani has nothing to disclose.
Massimo Filippi, MD, FAAN (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi;. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi- Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi 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 Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.
Federica Agosta (San Raffaele Scientific Institute)	Federica Agosta has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Philips. Federica Agosta has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier INC.