Cognitive and MRI Profiles in Primary and Secondary Progressive Multiple Sclerosis (P13-3.002)

Abstract

<h3>Objective:</h3> We examined the neuropsychological profile of primary progressive (PP) and secondary progressive (SP) multiple sclerosis (MS) patients and investigated the relationship between cognitive functioning with structural and functional MRI abnormalities. <h3>Background:</h3> Studies comparing frequency and patterns of cognitive dysfunction between PPMS and SPMS have yielded conflicting results. <h3>Design/Methods:</h3> One-hundred eighty-three MS patients (60 PPMS and 123 SPMS) and 75 age- and sex-matched healthy controls underwent 3.0T MRI. MS patients were administered the Brief Repeatable Battery of Neuropsychological tests (BRB-N) and were classified as cognitively impaired if they scored below the 5^th percentile of the normative sample on at least two tests. Four cognitive domain z-scores were determined from normative data, and then averaged to obtain a measure of global cognition (z-BRB-N). Using hierarchical linear regression analysis, the contribution of lesion volumes, normalized brain volumes, white matter fractional anisotropy (FA) and mean diffusivity (MD) abnormalities, and resting state (RS) functional connectivity (FC) alterations to global cognition in PPMS and SPMS was investigated. <h3>Results:</h3> Patients with PPMS and SPMS had similar z-scores in all investigated cognitive domains. Compared to PPMS, SPMS showed decreased FA and increased MD in the fornix, and lower RS FC within the basal ganglia network. The frequency of cognitive impairment was 31.7% in PPMS and 41.3% in SPMS (p=0.19). In PPMS, poorer cognitive performance (e.g., lower z-BRB-N) was associated with decreased FA of the medial lemniscus (ΔR²=0.11; p=0.011) and lower normalized gray matter volume (ΔR²=0.29; p&lt;0.001). In SPMS, poorer cognitive performance was associated with decreased FA of the fornix (ΔR²=0.35; p&lt;0.001) and lower normalized white matter volume (ΔR²=0.05; p=0.034). <h3>Conclusions:</h3> PPMS and SPMS had similar neuropsychological profile. Cognitive dysfunction in PPMS and SPMS was related to distinct patterns of structural MRI abnormalities and involvement of different white matter tracts, while RS FC alterations did not contribute to explain their global cognitive functioning. <b>Disclosure:</b> Damiano Mistri has nothing to disclose. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS Celgene. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIOMEDIA. Paola Valsasina has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ACCMED. Elisabetta Pagani has nothing to disclose. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. 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, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).