Abstract:
OBJECTIVE:To investigate whether vitamin D, smoking, and anti-Epstein-Barr virus (EBV) antibody concentrations predict long-term cognitive status and neuroaxonal injury in multiple sclerosis (MS). METHODS:This study was conducted among 278 patients with clinically isolated syndrome who participated in the clinical trial BENEFIT (Betaferon/Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment) and completed the 11-year assessment (BENEFIT-11). We measured serum 25-hydroxyvitamin-D (25(OH)D), cotinine (smoking biomarker), and anti-Epstein-Barr virus nuclear antigen 1 (EBNA-1) immunoglobulin G (IgG) at baseline and at months 6, 12, and 24 and examined whether these biomarkers contributed to predict Paced Auditory Serial Addition Test (PASAT)-3 scores and serum neurofilament light chain (NfL) concentrations at 11 years. Linear and logistic regression models were adjusted for sex, baseline age, treatment allocation, steroid treatment, multifocal symptoms, T2 lesions, and body mass index. RESULTS:Higher vitamin D predicted better, whereas smoking predicted worse cognitive performance. A 50-nmol/L higher mean 25(OH)D in the first 2 years was related to 65% lower odds of poorer PASAT performance at year 11 (95% confidence intervals [95% CIs]: 0.14-0.89). Standardized PASAT scores were lower in smokers and heavy smokers than nonsmokers (ptrend = 0.026). Baseline anti-EBNA-1 IgG levels did not predict cognitive performance (ptrend = 0.88). Associations with NfL concentrations at year 11 corroborated these findings-a 50-nmol/L higher mean 25(OH)D in the first 2 years was associated with 20% lower NfL (95% CI: -36% to 0%), whereas smokers had 20% higher NfL levels than nonsmokers (95% CI: 2%-40%). Anti-EBNA-1 antibodies were not associated with NfL. CONCLUSIONS:Lower vitamin D and smoking after clinical onset predicted worse long-term cognitive function and neuronal integrity in patients with MS.
journal_name
Neurologyjournal_title
Neurologyauthors
Cortese M,Munger KL,Martínez-Lapiscina EH,Barro C,Edan G,Freedman MS,Hartung HP,Montalbán X,Foley FW,Penner IK,Hemmer B,Fox EJ,Schippling S,Wicklein EM,Kappos L,Kuhle J,Ascherio A,BENEFIT Study Group.doi
10.1212/WNL.0000000000009371subject
Has Abstractpub_date
2020-05-05 00:00:00pages
e1950-e1960issue
18eissn
0028-3878issn
1526-632Xpii
WNL.0000000000009371journal_volume
94pub_type
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