Marianna Cortese

Preclinical disease activity in multiple sclerosis: A prospective study of cognitive performance prior to first symptom.

To prospectively investigate potential signs of preclinical multiple sclerosis (MS) activity and when they are present prior to first symptom using data from a historical cohort.

Level of education and multiple sclerosis risk after adjustment for known risk factors: The EnvIMS study.

Background: Several recent studies have found a higher risk of multiple sclerosis (MS) among people with a low level of education. This has been suggested to reflect an effect of smoking and lower vitamin D status in the social class associated with lower levels of education. Objective: The objective of this paper is to investigate the association between level of education and MS risk adjusting for the known risk factors smoking, infectious mononucleosis, indicators of vitamin D levels and body size. Methods: Within the case-control study on Environmental Factors In MS (EnvIMS), 953 MS patients and 1717 healthy controls from Norway reported educational level and history of exposure to putative environmental risk factors. Results: Higher level of education were associated with decreased MS risk (p trend = 0.001) with an OR of 0.53 (95% CI 0.41–0.68) when comparing those with the highest and lowest level of education. This association was only moderately reduced after adjusting for known risk factors (OR 0.61, 95% CI 0.44–0.83). The estimates remained similar when cases with disease onset before age 28 were excluded. Conclusion: These findings suggest that factors related to lower socioeconomic status other than established risk factors are associated with MS risk.

Timing of use of cod liver oil, a vitamin D source, and multiple sclerosis risk: The EnvIMS study.

Background: Low vitamin D levels have been associated with an increased risk of multiple sclerosis (MS), although it remains unknown whether this relationship varies by age. Objective: The objective of this paper is to investigate the association between vitamin D3 supplementation through cod liver oil at different postnatal ages and MS risk. Methods: In the Norwegian component of the multinational case-control study Environmental Factors In Multiple Sclerosis (EnvIMS), a total of 953 MS patients with maximum disease duration of 10 years and 1717 controls reported their cod liver oil use from childhood to adulthood. Results: Self-reported supplement use at ages 13–18 was associated with a reduced risk of MS (OR 0.67, 95% CI 0.52–0.86), whereas supplementation during childhood was not found to alter MS risk (OR 1.01, 95% CI 0.81–1.26), each compared to non-use during the respective period. An inverse association was found between MS risk and the dose of cod liver oil during adolescence, suggesting a dose-response relationship (p trend = 0.001) with the strongest effect for an estimated vitamin D3 intake of 600–800 IU/d (OR 0.46, 95% CI 0.31–0.70). Conclusions: These findings not only support the hypothesis relating to low vitamin D as a risk factor for MS, but further point to adolescence as an important susceptibility period for adult-onset MS.

Physical activity is associated with a decreased multiple sclerosis risk: The EnvIMS study:

Background: The lifestyle factors smoking and obesity have been associated with the risk of multiple sclerosis (MS). Physical activity (PA) may also be of importance. Objective: To examine the association between PA and MS risk in Italy, Norway, and Sweden and to evaluate the possible influence by established risk factors. Methods: In this case–control study, 1904 cases and 3694 controls were asked to report their average weekly amounts of light and vigorous PA during adolescence on a scale ranging from none to more than 3 hours activity. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and adjusted for potential confounders. Results: Vigorous PA was inversely associated with MS risk in the pooled analysis (p-trend < 0.001) with an age- and sex-adjusted OR of 0.74 (95% CI: 0.63–0.87) when comparing the highest and lowest levels. Adjusting for outdoor activity, infectious mononucleosis, body size, and smoking yielded similar results. The association was present in all countries and was not affected by exclusion of patients with early disease onset. Light PA was not associated with the risk of MS. Conclusion: Our findings suggest that vigorous PA can modify the risk of developing MS independent of established risk factors.

Negative interaction between smoking and EBV in the risk of multiple sclerosis: The EnvIMS study

Background: Results from previous studies on a possible interaction between smoking and Epstein–Barr virus (EBV) in the risk of multiple sclerosis (MS) are conflicting. Objectives: To examine the interaction between smoking and infectious mononucleosis (IM) in the risk of MS. Methods: Within the case–control study on Environmental Factors In Multiple Sclerosis (EnvIMS), 1904 MS patients and 3694 population-based frequency-matched healthy controls from Norway, Italy, and Sweden reported on prior exposure to smoking and history of IM. We examined the interaction between the two exposures on the additive and multiplicative scale. Results: Smoking and IM were each found to be associated with an increased MS risk in all three countries, and there was a negative multiplicative interaction between the two exposures in each country separately as well as in the pooled analysis (p = 0.001). Among those who reported IM, there was no increased risk associated with smoking (odds ratio (OR): 0.95, 95% confidence interval (CI): 0.66–1.37). The direction of the estimated interactions on the additive scale was consistent with a negative interaction in all three countries (relative excess risk due to interaction (RERI): −0.98, 95% CI: −2.05–0.15, p = 0.09). Conclusion: Our findings indicate competing antagonism, where the two exposures compete to affect the outcome.

Body size and physical exercise, and the risk of multiple sclerosis:

Background: Whether large body size increases multiple sclerosis (MS) risk in men is not well understood. Concurrently, physical exercise could be an independent protective factor. Objective: To prospectively investigate the association between body mass index (BMI) and aerobic fitness, indicators of body size and exercise, and MS risk in men. Methods: We performed a population-based nested case-control study within the historical cohort of all Norwegian men, born in 1950–1975, undergoing mandatory conscription at the age of 19 years. 1016 cases were identified through linkage to the Norwegian MS registry, while 19,230 controls were randomly selected from the cohort. We estimated the effect of BMI and fitness at conscription on MS risk using Cox regression. Results: Higher BMI (≥25 vs 18.5–<25 kg/m2) was significantly associated with increased MS risk (adjusted relative risk (RRadj) = 1.36, 95% confidence interval (CI): 1.05–1.76). We also found a significant inverse association between aerobic fitness (high vs low) and MS risk independent of BMI (RRadj = 0.69, 95% CI: 0.55–0.88, p-trend = 0.003), remaining similar when men with MS onset within 10 years from conscription were excluded (p-trend = 0.03). Conclusion: These findings add weight to evidence linking being overweight to an increased MS risk in men. Furthermore, they suggest that exercise may be an additional modifiable protective factor for MS.

Urate and the risk of Parkinson's disease in men and women

INTRODUCTION High urate levels have consistently been associated with lower Parkinsons disease (PD) risk among men, but the association is less clear among women. In this study we prospectively investigated the association between high uric acid levels and PD, evaluating potential differences by sex and age. METHODS This historical cohort study included the entire Norwegian population alive and at least 18 years old on 01/01/2004. We retrieved use of urate-lowering drugs, a marker of high urate levels/gout, from the Norwegian Prescription Database, and followed individuals from 01/01/2005 to PD onset, emigration, death, or end of follow-up on 31/12/2013. We identified 4523 incident PD cases during follow-up, and used Cox regression to estimate hazard ratios (HRadj) and 95% confidence intervals (CI), adjusting for sex, age, and level of education. We also tested for effect modification by sex and age. RESULTS Exposure to urate-lowering drugs was associated with a significantly lower PD risk (HRadj = 0.80, 95% CI: 0.68-0.95). The association was more marked in men (HRadj = 0.77, 95% CI: 0.63-0.94), compared to women (HRadj = 0.89, 95% CI: 0.65-1.22), but the difference was not significant (p for effect modification = 0.61). The association varied significantly by age among women (p = 0.01) with a protective effect suggested only at higher age (above 70 years) when urate levels are higher than premenopausally (HR = 0.65, 95% CI: 0.41-1.03), but not in men (p = 0.61). CONCLUSION These findings suggest that urate may be protective against PD in both men and women.

Diet quality and risk of multiple sclerosis in two cohorts of US women

Objective: To determine the association between measures of overall diet quality (dietary indices/patterns) and risk of multiple sclerosis (MS). Methods: Over 185,000 women in the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII) completed semiquantitative food frequency questionnaires every 4 years. There were 480 MS incident cases. Diet quality was assessed using the Alternative Healthy Eating Index-2010 (AHEI-2010), Alternate Mediterranean Diet (aMED) index, and Dietary Approaches to Stop Hypertension (DASH) index. Principal component analysis was used to determine major dietary patterns. We calculated the hazard ratio (HR) of MS with Cox multivariate models adjusted for age, latitude of residence at age 15, body mass index at age 18, supplemental vitamin D intake, and cigarette smoking. Results: None of the dietary indices, AHEI-2010, aMED, or DASH, at baseline was statistically significantly related to the risk of MS. The principal component analysis identified “Western” and “prudent” dietary patterns, neither of which was associated with MS risk (HR, top vs bottom quintile: Western, 0.81 (p = 0.31) and prudent, 0.96 (p = 0.94)). When the analysis was repeated using cumulative average dietary pattern scores, the results were unchanged. Conclusion: There was no evidence of an association between overall diet quality and risk of developing MS among women.

Diabetes is associated with decreased migraine risk: A nationwide cohort study

Background Results from studies on diabetes and migraine risk are conflicting, which may be due to methodological limitations. Prospective studies with long follow-up could increase our understanding of the relationship between the two diseases. Method We performed a cohort study including the whole Norwegian population alive on 01.01.2004, using prescriptions registered in the Norwegian prescription database to identify individuals developing type 1 diabetes, type 2 diabetes and migraine during follow-up (10 years). We used Cox proportional hazards regression to estimate rate ratios with corresponding 95% confidence intervals for the effect of diabetes on migraine risk, adjusting for age, sex, and educational level. Result We identified 7,883 type 1 diabetes patients and 93,600 type 2 patients during the study period. Type 1 diabetes was significantly associated with a subsequent decreased migraine risk during follow-up in the age- and sex-adjusted analyses (0.74; 0.61–0.89). Type 2 diabetes was also associated with a significantly lower migraine risk (0.89; 0.83–0.95). Further adjustment for educational level yielded similar results for both diabetes. Conclusion Both type 1 and type 2 diabetes were significantly associated with a decreased risk of migraine. This suggests that diabetes or diabetes treatment may have a protective effect on the development of migraine.