Abstract Details

Title Serum neurofilament light chain levels and cognitive performance in multiple sclerosis: a longitudinal retrospective 5-year study

Topic Multiple Sclerosis

Presentation(s) S37 - MS Biomarkers (1:11 PM-1:22 PM)

Poster/Presentation
Number 002

Background The neurodegenerative pathology in MS patients is associated with poorer cognitive performance. sNfL is an emerging biomarker of neuroaxonal injury.

Objective To assess the associations between serum neurofilament light chain (sNfL) levels and cognitive performance in multiple sclerosis (MS) patients and age-matched healthy controls (HCs) over 5 years.

Design/Methods 127 MS patients (85 relapsing-remitting MS and 42 progressive MS), 20 clinically isolated syndrome (CIS) patients and 52 HCs were followed for a mean of 5.5 years. At baseline and follow-up, the sNfL levels were measured using sensitive Simoa assay and quantified in pg/ml. At the follow-up, the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) was utilized and scores regarding processing speed, verbal, and visuospatial memory were obtained. Cognitively impaired (CI) status was derived using HC-based z-scores. ANCOVA and regression models adjusted for age and years of education were used.

Results

Follow-up sNfL levels were associated with poorer processing speed performance (β=-0.228, p=0.024) and visuospatial memory (β=-0.284, p=0.024) in MS patients. Baseline sNfL levels predicted poorer processing speed (β=-0.185, p=0.04) and verbal memory (β=-0.199, p=0.027) 5 years later. CI MS patients had higher sNfL levels (mean 35.8 vs. 24.4, p=0.019), after adjusting for age and disease duration. Over 5 years, the CI MS patients had higher absolute increase in sNfL when compared the non-CI MS patients (mean 6.4 vs. 0.9, p=0.04). Patients with follow-up sNfL ≥30 pg/ml (n=46) had poorer processing speed performance when compared to patients with <30 pg/ml (43.7 vs. 51.9, p=0.024). In the HCs, the follow-up sNfL levels showed associations with processing speed (β=-0.316, p=0.036) and visuospatial memory (β=-0.499, p=0.001).

Conclusions Higher sNfL levels are associated with poorer processing speed and visuospatial memory performance in both the MS patients and HCs. Within the MS group, baseline sNfL levels are associated with future poorer processing speed performance.

Authors/Disclosures
Dejan Jakimovski, MD, PhD (Buffalo Neuroimaging Analysis Center, University at Buffalo) PRESENTER	Dr. Jakimovski has nothing to disclose.
Robert Zivadinov, MD, PhD, FAAN (Buffalo Neuroimaging Analysis Center)	The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Omnicuris. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Myrobalan. Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Zivadinov has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bristol Myers Squibb. The institution of Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen.
Murali Ramanathan, PhD (University At Buffalo)	The institution of Dr. Ramanathan has received research support from DoD. Dr. Ramanathan has received publishing royalties from a publication relating to health care.
Jesper Hagemeier	No disclosure on file
Bianca Weinstock-Guttman, MD (Department of Neurology, University At Buffalo)	Dr. Weinstock-Guttman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme &Sanofi. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving as a Reviewer with NIH.
Davorka Tomic	Davorka Tomic has stock in Meck KGaA.
Harald Kropshofer	Harald Kropshofer has nothing to disclose.
Christian Barro, MD, PhD (Brigham and Women's Hospital)	Dr. Barro has nothing to disclose.
David Leppert, MD (University Hospital Basel)	Dr. Leppert has received personal compensation for serving as an employee of GeNeuro. Dr. Leppert has received personal compensation for serving as an employee of GeNeuro. Dr. Leppert has received personal compensation for serving as an employee of Geneuro. Dr. Leppert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Leppert has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Leppert has received personal compensation in the range of $0-$499 for serving as a Consultant for Orion. Dr. Leppert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Leppert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Quanterix. Dr. Leppert has stock in Novartis.
	No disclosure on file
Jens Kuhle, MD	Dr. Kuhle has nothing to disclose.
Ralph H. Benedict, PhD (University At Buffalo)	Dr. Benedict has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Benedict has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Roche. Dr. Benedict has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Benedict has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Benedict has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Bristol Meyers Squibb. Dr. Benedict has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Benedict has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Benedict has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Brystal Mier Squibb. Dr. Benedict has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for EMD Serono. The institution of Dr. Benedict has received research support from Genzyme. The institution of Dr. Benedict has received research support from Biogen. The institution of Dr. Benedict has received research support from Bristol Myer Squib. Dr. Benedict has received intellectual property interests from a discovery or technology relating to health care.

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