#ECTRIMS2018 — High Vitamin D Levels, Smoking Predict Opposite Effects on Cognition in CIS Patients, Study Suggests

High vitamin D levels predict better cognitive function, while smoking is associated with worse long-term cognitive disability in patients with clinically isolated syndrome (CIS), a study suggests.

Data from the study was presented by Marianna Cortese, MD, PhD, from the Department of Nutrition, Harvard T.H. Chan School of Public Health, at the 34th congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) recently held in Berlin.

The presentation was titled “Vitamin D, smoking, EBV and long-term cognitive performance among CIS patients: 11-year follow-up of BENEFIT.”

Cognitive issues are a common symptom and a significant cause of disability in multiple sclerosis (MS) patients. These changes can weigh considerably on a person’s quality of life, and they often are the primary reason why MS patients decide to leave their jobs.

However, it is unknown if factors thought to increase MS risk also predict long-term cognitive decline in patients, specifically, the so-called modifiable factors — factors for which a person can take measures to change.

Typically, modifiable factors are environmental factors including smoking, vitamin D levels, sun exposure, obesity, and viral or bacterial infections.

To better understand the impact of some of these factors on cognition, a team led by researchers at the Harvard T.H. Chan School of Public Health and Brigham and Women’s Hospital, both in Boston, studied if vitamin D, smoking, and Epstein-Barr virus (EBV) infection were able to predict long-term cognitive changes in patients with CIS, a condition that is thought to indicate a first course in MS.

Researchers analyzed data from 278 CIS patients, who were enrolled in a Phase 3 trial called BENEFIT (NCT00185211), which looked at the long-term effects of treatment with Betaseron/Betaferon (interferon beta 1b). Patients were followed for 11 years.

Serum levels of vitamin D using the 25-hydroxy vitamin D test, cotinine (a marker for smoking), and EBV nuclear-antigen 1 (a biomarker of recent or current EBV infection) were assessed at the study start and at six, 12 and 24 months of follow-up. Vitamin D was also measured at five and 11 years. Serum neurofilament light chain (NfL, a marker of neuronal injury) was measured at 11 years of follow-up.

Cognitive function was assessed by the Paced Auditory Serial Addition Test (PASAT-3), which assesses speed and flexibility of auditory information processing, as well as calculation ability. The lower the PASAT score, the worse a person’s cognitive function. 

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Higher vitamin D levels were seen to predict better long-term cognitive function in CIS patients, while smoking predicted worse cognitive function. With each increase in vitamin D levels of 50 nanomolars per liter (nmol/L) within the first two years, patients had a 65% lower chance of scoring worse on the PASAT test at year 11. 

In contrast, cognitive function was significantly decreased (indicated by lower PASAT scores) in smokers and heavy smokers, compared with non-smokers.

EBV infection after disease onset was not associated with changes in cognitive function.

Comparing the previous parameters with the extent of neuronal damage (surrogate marker NfL) at 11 years confirmed most of the previous findings. An increase in vitamin D of 50 nmol/L was associated with a 20% lower NfL level, suggesting less neuron damage. In contrast, smokers had 29% higher NfL levels than non-smokers.

EBV infection was not associated with the marker of neuronal damage, suggesting it has no impact on the patient’s “cognitive status or neuronal injury at year 11,” Cortese said in the presentation. 

Based on these results, Cortese concluded that “higher vitamin D in the first years after CIS was associated with a better cognitive function and lower neuronal injury at year 11,” while smoking “was associated with worse cognitive function and higher neuronal injury at year 11.”

According to her, “smoking cessation is important” in this patient population, and “vitamin D supplementation might be neuroprotective.”