BERLIN — Higher vitamin D levels at the time of a diagnosis of a clinically isolated syndrome (CIS) were associated with better cognitive performance 11 years later. In contrast, cigarette smoking was linked to worse long-term cognition.
Seropositivity for Epstein-Barr virus (EBV) infection showed no significant association with cognition, reported investigators for the Betaferon/Betaseron in Newly Emerging MS for Initial Treatment 11 Year (BENEFIT-11) trial.
“Higher vitamin D in the first years after clinically isolated syndrome was associated with better cognitive function and lower neuronal injury at year 11,” said Mariana Cortese, MD, PhD, of the Department of Nutrition at the Harvard T. H. Chan School of Public Health in Boston.
Conversely, cigarette smoking in the first 2 years after CIS was associated with worse long-term cognitive performance on neurologic testing and higher neuronal injury, she told attendees during a packed late-breaking abstract session here at the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2018.
A Common Clinical Conundrum
Those affected are more likely to become unemployed and/or stop engaging in social activities. Each can worsen quality of life. In addition, the cognitive dysfunction is often progressive, and there is no established treatment.
Cortese and colleagues followed up on 278 CIS patients, a subpopulation of the original multicenter, double-blind, 2-year, randomized controlled BENEFIT trial.
The investigators evaluated seasonally adjusted vitamin D levels, measured by serum levels of 25-hydroxyvitamin D; smoking status, determined on the basis of the tobacco biomarker cotinine (<10 ng/mL, nonsmoker; >25 ng/mL, smoker; >189 ng/mL, heavy smoker); and EBV nuclear antigen–1 (EBNA-1) immunoglobulin G levels, which were used as a marker for EBV exposure.
Cognitive performance at 11 years was measured using the Paced Auditory Serial Addition Test (PASAT-3).
Within the first 2 years post CIS diagnosis, each 50 nmol/L increase in mean vitamin D level was associated with a 65% lower risk of scoring below the median on the PASAT-3 at year 11 (odds ratio, 0.35; 95% confidence interval [CI], 0.14 – 0.89; P = .027).
“Higher quintiles of 25-hydroxyvitamin D were associated with scoring better on the PASAT,” Cortese said.
In addition, standardized PASAT-3 scores were lower among smokers (ß = -0.26; 95% CI, -0.69 to 0.17) and heavy smokers in all measurements (ß = -0.81; 95% CI, -1.60 to -0.02) compared with nonsmokers (P-trend = .036).
The linear trend from nonsmokers to heavy smokers “indicates a dose relationship,” she said. “We found up to 6 lower PASAT points at year 11 among heavy smokers, so the findings are clinically meaningful.”
EBNA-1 IgG antibodies were not, in contrast, associated with cognitive function at year 11 (P-trend across quartiles = 0.73).
Shining a Light on Neuronal Injury
Cortese and colleagues also assessed neuron-axonal injury through serum neurofilament light (sNfL) levels. Higher sNfL levels indicate greater injury.
They found each 50 nmol/L increase in mean 25-hydroxyvitamin D levels in the first 2 years post CIS diagnosis was associated with 20% lower sNfL levels (95% CI, 0.64 – 0.99; P = .05).
In addition, sNfL levels were 29% higher in smokers had compared to nonsmokers (95% CI, 1.08 – 1.54; P = .006).
Again, EBNA-1 levels were not associated with sNfL findings. “The serum NfL results corroborate the main findings,” she said.
On the basis of the BENEFIT-11 results, Cortese said, “Vitamin D supplementation in first years might be neuroprotective.” She added, “Smoking cessation counseling is also important.”
“It was a great study and should open further investigations,” session comoderator Letizia Leocani, MD, PhD, of the Department of Neurology at the Università Vita-Salute San Raffaele-UniSRin Milan, Italy, told Medscape Medical News when asked to comment on the study.
The researchers found an association and not causation, she cautioned. In addition, they measured cognitive performance at 11 years and not at baseline, which would have been interesting to compare, she added.
Martin Stangel, MD, of the Department of Clinical Neuroimmunology and Neurochemistry at Hannover Medical School in Germany, said the study indicates “vitamin D elevation and cessation of smoking may preserve cognitive function.”
The results are also important because “vitamin D and smoking are factors that can be modified,” he said during a clinical highlights session at ECTRIM 2018.
The study was supported through grants from the National Institute of Neurological Disorders and Stroke and the National Multiple Sclerosis Society. Bayer Healthcare provided blood sample testing for vitamin D at no cost. Dr Cortese, Dr Leocani, and Dr Stangel have disclosed no relevant financial relationships.