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Abstract Details

Identifying distinct cognitive phenotypes in multiple sclerosis
Multiple Sclerosis
S28 - Clinical Decision Making in MS (2:00 PM-2:08 PM)
001

Cognitive impairment is a common and disabling feature of MS, but a precise characterization of cognitive phenotypes in MS patients is still lacking.

We sought to define homogeneous cognitive phenotypes in a large cohort of multiple sclerosis (MS) patients by using a data-driven approach, and to assess their distinctive clinical and MRI features. Our aim was to go beyond traditional preserved/impaired classification dichotomy, setting the stage for future research and tailored management approaches.

A cohort of 1212 MS patients and 196 healthy controls (HC) from 8 Italian MS centers underwent cognitive evaluation with Rao’s Brief Repeatable Battery and Stroop Color Word Test. A subgroup (172 MS patients and 50 HC) also underwent a 3T MRI examination, including 3D T1-weighted and dual-echo sequences. Latent-profile analysis was used on cognitive tests’ z-scores for identifying cognitive phenotypes. Linear regression and mixed effects models were used to define the clinical and MRI features of each phenotype.

Five cognitive phenotypes were identified: “preserved-cognition” (19%), “mild verbal memory/semantic fluency” (30%), “mild-multi-domain” (19%), “severe-attention/executive” (14%), and “severe-multi-domain” (18%) involvement. “Preserved cognition” and “mild-verbal memory/semantic fluency” patients were younger and had shorter disease duration compared to the other phenotypes. Physical disability was lowest in “preserved cognition” and highest in “severe-multi-domain” patients. Severe cognitive phenotypes prevailed in progressive patients. At MRI evaluation, compared to “preserved-cognition”, “mild verbal memory/semantic fluency” patients exhibited reduced hippocampal volume, “mild-multi-domain” reduced cortical gray matter volume, “severe-attention/executive” higher T2-hyperintense lesion volume and “severe-multi-domain” extensive brain damage.

By defining homogenous and clinically-meaningful phenotypes, this study can pave the way to future research on neuroanatomical substrates of MS-related cognitive impairment and help define tailored management strategies.

Authors/Disclosures
Ermelinda De Meo (San Raffaele, Vita-Salute University, Milan)
PRESENTER
Ms. De Meo has nothing to disclose.
Emilio Portaccio Emilio Portaccio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Emilio Portaccio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono. Emilio Portaccio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Emilio Portaccio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Emilio Portaccio has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Emilio Portaccio has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Biogen. Emilio Portaccio has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck Serono. Emilio Portaccio has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Emilio Portaccio has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Emilio Portaccio has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen. Emilio Portaccio has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS Cellgene.
Antonio Giorgio, MD Dr. Giorgio has nothing to disclose.
No disclosure on file
No disclosure on file
No disclosure on file
Francesco Patti, MD Dr. Patti has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. The institution of Dr. Patti has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Almirall. Dr. Patti has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Meyers. Dr. Patti has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson and Johnson. The institution of Dr. Patti has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck. The institution of Dr. Patti has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Patti has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. The institution of Dr. Patti has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Patti has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Almirall, Bayer, Biogen, Bristol Meyers and Squibb Merck, Roche, Sanofi, TEVA. Dr. Patti has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for University of Catania and AISM/FISM, Fondazione Italiana Sclerosi Multipla. Dr. Patti has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Neurology.
Clara Chisari, MD Clara Chisari, MD has nothing to disclose.
Paolo Gallo, MD (Dompe' Biotec Italy) Dr. Gallo has nothing to disclose.
No disclosure on file
Angelo Ghezzi, MD No disclosure on file
No disclosure on file
Flavia Mattioli, MD (University of Brescia) Dr. Mattioli has nothing to disclose.
No disclosure on file
Marta Simone Marta Simone, 11772 has nothing to disclose.
No disclosure on file
No disclosure on file
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.
Nicola De Stefano, MD (University of Siena) Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck Healthcare KGaA. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunic AG. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis Pharma AG. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck Serono S.p.A. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche S.p.A.. The institution of Dr. De Stefano has received research support from Italian MS Society. The institution of Dr. De Stefano has received research support from Merck Healthcare KGaA.
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 P. Amato, PhD (Ospedale Di Careggi) Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation for serving as an employee of AOU Careggi. Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Genzyme. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi genzyme. The institution of Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene BMS. The institution of Dr. Amato has received research support from Merck. The institution of Dr. Amato has received research support from Biogen. The institution of Dr. Amato has received research support from Roche.