Abstract Details

Title Altered Resting State Dynamic Functional Connectivity of the Precuneus Contributes to Cognition and Depression in Neuromyelitis Optica

Topic Aging, Dementia, and Behavioral Neurology

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

Poster/Presentation
Number 018

Objective

To explore the contribution of dynamic functional connectivity (dFC) of the precuneus (PCUN) at resting state (RS) to cognitive alterations in neuromyelitis optica spectrum disorders (NMOSD).

Background In NMOSD, cognitive impairment (CI) is considered as a unique relapse-unrelated manifestation of the disease. Anti-aquaporin4 (AQP4)-IgG seems to inhibit neuronal plasticity and long-term potentiation. Structural and functional MRI (fMRI) studies have disclosed an association between damage of the PCUN and cognitive impairment CI in several neurological conditions.

Design/Methods 3.0 T RS fMRI were acquired from 27 AQP4-positive NMOSD patients and 30 age- and sex-matched healthy controls (HC), undergoing a neuropsychological evaluation including global and domain-specific cognitive impairment indexes (CII) and Beck Depression Inventory II (BDI-II) scores. DFC of bilateral PCUN was assessed by means of sliding-window seed-voxel correlation analysis. Standard deviation of dFC across windows was used as a measure of dynamicity (the higher the better). Age- and sex-adjusted between-group dFC comparisons and correlations with cognitive scores were assessed using full-factorial models.

Results Compared to HC, patients had reduced PCUN-dFC with caudate nucleus, superior temporal gyrus, rectus/olfactory bulb, middle/inferior occipital gyri, supplemental motor area, cerebellum and periacqueductal gray matter. Conversely, an increased dFC in the PCUN and between PCUN and thalamus, putamen, middle temporal gyrus, rolandic operculum and parahippocampus was observed. Sixty-three% of patients had depressive symptoms, with BDI-II score positively correlating with intra-PCUN-dFC and its connectivity with insula, rolandic operculum, middle temporal pole and several cerebellar regions. Forty-four% of patients had CI and information processing speed (IPS) was the most affected domain (59.2%). Global CII positively correlated with PCUN-dFC with hippocampus, amygdala and middle frontal gyrus.

Conclusions PCUN dFC supports the role of PCUN in cognitive performance in NMOSD. We observed a negative effect of higher dynamic connections with the temporal pole for cognition and with limbic and cerebellar regions for depressive symptoms.

Authors/Disclosures
Laura Cacciaguerra, MD, PhD (Mayo Clinic) PRESENTER	Dr. Cacciaguerra has nothing to disclose.
Damiano Mistri, MSC (Università Vita-Salute San Raffaele)	Mr. Mistri has nothing to disclose.
Paola Valsasina	No disclosure on file
Vittorio Martinelli (S. Raffaele Hospital)	Dr. Martinelli has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis, Biogen, Sanofi Genzyme, TEVA and Merck. Dr. Martinelli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck .
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 $10,000-$49,999 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.
Maria A. Rocca (Neuroimaging Research Unit)	Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. The institution of Maria Assunta Rocca has received research support from MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.

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