Consumption of Olive Oil and Diet Quality and Risk of Dementia-Related Death.

Importance: Age-standardized dementia mortality rates are on the rise. Whether long-term consumption of olive oil and diet quality are associated with dementia-related death is unknown. Objective: To examine the association of olive oil intake with the subsequent risk of dementia-related death and assess the joint association with diet quality and substitution for other fats. Design, Setting, and Participants: This prospective cohort study examined data from the Nurses' Health Study (NHS; 1990-2018) and Health Professionals Follow-Up Study (HPFS; 1990-2018). The population included women from the NHS and men from the HPFS who were free of cardiovascular disease and cancer at baseline. Data were analyzed from May 2022 to July 2023. Exposures: Olive oil intake was assessed every 4 years using a food frequency questionnaire and categorized as (1) never or less than once per month, (2) greater than 0 to less than or equal to 4.5 g/d, (3) greater than 4.5 g/d to less than or equal to 7 g/d, and (4) greater than 7 g/d. Diet quality was based on the Alternative Healthy Eating Index and Mediterranean Diet score. Main Outcome and Measure: Dementia death was ascertained from death records. Multivariable Cox proportional hazards regressions were used to estimate hazard ratios (HRs) and 95% CIs adjusted for confounders including genetic, sociodemographic, and lifestyle factors. Results: Of 92 383 participants, 60 582 (65.6%) were women and the mean (SD) age was 56.4 (8.0) years. During 28 years of follow-up (2 183 095 person-years), 4751 dementia-related deaths occurred. Individuals who were homozygous for the apolipoprotein ε4 (APOE ε4) allele were 5 to 9 times more likely to die with dementia. Consuming at least 7 g/d of olive oil was associated with a 28% lower risk of dementia-related death (adjusted pooled HR, 0.72 [95% CI, 0.64-0.81]) compared with never or rarely consuming olive oil (P for trend < .001); results were consistent after further adjustment for APOE ε4. No interaction by diet quality scores was found. In modeled substitution analyses, replacing 5 g/d of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8% (95% CI, 4%-12%) to 14% (95% CI, 7%-20%) lower risk of dementia mortality. Substitutions for other vegetable oils or butter were not significant. Conclusions and Relevance: In US adults, higher olive oil intake was associated with a lower risk of dementia-related mortality, irrespective of diet quality. Beyond heart health, the findings extend the current dietary recommendations of choosing olive oil and other vegetable oils for cognitive-related health.

Serologic Response to the Epstein-Barr Virus Peptidome and the Risk for Multiple Sclerosis.

Importance: It remains unclear why only a small proportion of individuals infected with the Epstein-Barr virus (EBV) develop multiple sclerosis (MS) and what the underlying mechanisms are. Objective: To assess the serologic response to all EBV peptides before the first symptoms of MS occur, determine whether the disease is associated with a distinct immune response to EBV, and evaluate whether specific EBV epitopes drive this response. Design, Setting, and Participants: In this prospective, nested case-control study, individuals were selected among US military personnel with serum samples stored in the US Department of Defense Serum Repository. Individuals with MS had serum collected at a median 1 year before onset (reported to the military in 2000-2011) and were matched to controls for age, sex, race and ethnicity, blood collection, and military branch. No individuals were excluded. The data were analyzed between September 1, 2022, and August 31, 2023. Exposure: Antibodies (enrichment z scores) to the human virome measured using VirScan (phage-displayed immunoprecipitation and sequencing). Main Outcome and Measure: Rate ratios (RRs) for MS for antibodies to 2263 EBV peptides (the EBV peptidome) were estimated using conditional logistic regression, adjusting for total anti-EBV nuclear antigen 1 (EBNA-1) antibodies, which have consistently been associated with a higher MS risk. The role of antibodies against other viral peptides was also explored. Results: A total of 30 individuals with MS were matched with 30 controls. Mean (SD) age at sample collection was 27.8 (6.5) years; 46 of 60 participants (76.7%) were male. The antibody response to the EBV peptidome was stronger in individuals with MS, but without a discernible pattern. The antibody responses to 66 EBV peptides, the majority mapping to EBNA antigens, were significantly higher in preonset sera from individuals with MS (RR of highest vs lowest tertile of antibody enrichment, 33.4; 95% CI, 2.5-448.4; P for trend = .008). Higher total anti-EBNA-1 antibodies were also associated with an elevated MS risk (top vs bottom tertile: RR, 27.6; 95% CI, 2.3-327.6; P for trend = .008). After adjusting for total anti-EBNA-1 antibodies, risk estimates from most EBV peptides analyses were attenuated, with 4 remaining significantly associated with MS, the strongest within EBNA-6/EBNA-3C, while the association between total anti-EBNA-1 antibodies and MS persisted. Conclusion and Relevance: These findings suggest that antibody response to EBNA-1 may be the strongest serologic risk factor for MS. No single EBV peptide stood out as being selectively targeted in individuals with MS but not controls. Larger investigations are needed to explore possible heterogeneity of anti-EBV humoral immunity in MS.

Antiviral therapy with tenofovir in MS.

Infection by the Epstein-Barr virus (EBV) is implicated as the leading cause of multiple sclerosis (MS). We have previously published a case description of a person with MS (pwMS) who was also HIV positive and treated with a combination of antiretrovirals (ART) containing tenofovir, a potent inhibitor of EBV replication. In the years following this publication, the patient had no new relapses, even though she did not use any MS disease-modifying therapy for nearly five years. After switching to another ART with no known efficacy against EBV, her MS-disease activity gradually re-emerged. This finding further emphasizes that targeting EBV lytic reactivation should be explored further in clinical trials as a potential treatment option for MS.

Flavonoid intake and risk of Parkinson's disease.

BACKGROUND: Flavonoids have been proposed to reduce the risk of Parkinson's disease (PD). However, results from epidemiological studies have been inconclusive. OBJECTIVE: To prospectively examine the association between the intake of flavonoids and their subclasses and the risk of PD and how pesticides may confound or modify that association. METHODS: The study population comprised 80 701 women (1984-2016) and 48 782 men (1986-2016) from two large US cohorts. Flavonoid intake was ascertained at baseline and every 4 years thereafter using a semiquantitative Food Frequency Questionnaire. We conducted multivariable-adjusted Cox regression models to estimate HRs and 95% CIs of PD according to quintiles of baseline and cumulative average intakes of flavonoids and subclasses. We repeated the analyses, adjusting for intakes of high-pesticide-residue fruits and vegetables (FVs) and stratifying by servings/day of high-pesticide-residue FV intake. RESULTS: We identified 676 incident PD cases in women and 714 in men after 30-32 years of follow-up. Higher total flavonoid intake at baseline was not associated with a lower PD risk, neither in men (HR comparing highest to lowest quintile: 0.89, 95% CI: 0.69 to 1.14) nor in women (HR comparing highest to lowest quintile: 1.27, 95% CI: 0.98 to 1.64). Similar results were observed for cumulative average intakes and flavonoid subclasses. Results remained similar after adjustment for and stratification by high-pesticide-residue FV and when analyses were restricted to younger PD cases. CONCLUSION: These results do not support a protective effect of flavonoid intake on PD risk. Pesticide residues do not confound or modify the association.

Smoking and multiple sclerosis risk in black people: A nested case-control study.

BACKGROUND: Smoking is a well-established risk factor for MS; however, it is not known whether its effect on disease risk varies by race/ethnicity. METHODS: We conducted a nested case-control study among US military personnel who have serum samples stored at the Department of Defense Serum Repository. We measured serum cotinine levels, a marker of tobacco smoke exposure, in 157 Black and 23 White individuals who developed MS during follow-up. Controls were randomly selected and matched to each case by age, sex, race/ethnicity, dates of sample collection, and branch of military service. RESULTS: Smoking was not associated with an increased risk of MS in Black people (RR: 1.08, 95 % CI: 0.63-1.85). The results remained similar in analyses restricted to smoking status at baseline, to samples collected 5 years before symptom onset, and using different cut-off levels in cotinine to define smoking status. Smoking was not statistically significantly associated with MS risk in White people, but the point estimate was similar to what has previously been reported in other studies (RR: 1.85, 95 % CI: 0.56-6.16). CONCLUSIONS: Smoking was not associated with MS risk in Black people. Given the consistent association between smoking and MS risk in predominantly White populations, this may suggest that the association between smoking and MS varies by race/ethnicity.

Hair color, family history of melanoma, and the risk of Parkinson's disease: An analysis update.

BACKGROUND: A shared biological component between melanoma and Parkinson's disease (PD) has been suggested. Yet, epidemiological evidence is scarce. OBJECTIVE: To examine the association of hair color and family history of melanoma, two strong predictors of melanoma risk, with the occurrence of PD. METHODS: We followed 131,342 women and men for ∼30 years for the development of PD. We calculated the cumulative incidence of PD from ages 40 to 90 according to hair color, and estimated the hazard ratio of PD according to hair color and family history of melanoma. RESULTS: Hair color was not strongly associated with the risk of PD, especially at advanced ages. In contrast, individuals with a family history of melanoma had a 1.4-fold higher risk of PD compared to those without a history. CONCLUSIONS: Our results support the hypothesis of a shared biological component between PD and melanoma. Both pigmentary and non-pigmentary pathways may play a role.

Association Between Use of Any of the Drugs Prescribed in Norway and the Subsequent Risk of Parkinson Disease: A Drug-wide Association Study.

BACKGROUND AND OBJECTIVES: The incidence rate of Parkinson disease (PD) has been increasing rapidly during the past years. Yet, no treatments exist to prevent or slow the progression of the disease. Moreover, we are unable to detect early disease stages during which intervention with disease-modifying therapies is most likely to succeed. The objective of this study was to perform an agnostic drug-wide association study estimating the association between the use of any of the drugs prescribed in Norway and the subsequent risk of PD. METHODS: This registry-based cohort study use data from the entire Norwegian population between 2004 and 2019 linked to the Norwegian Prescription Registry, with more than 600 million individual prescriptions. Drug classes were screened according to Anatomical Therapeutic Chemical codes at level 2, corresponding to therapeutic subgroups. We used Cox regression models to estimate hazard ratios (HRs) and 95% CIs for the associations between drug classes and PD risk. All p values were corrected for multiple testing using the false discovery rate. In addition, we conducted sensitivity analyses of exposure definition as well as time-lag and dose-response analyses. RESULTS: The study population comprised 3,223,672 individuals, 15,849 of whom developed PD during the follow-up. We identified 31 drug classes that were statistically significantly associated with PD risk in Norway during the follow-up. Drugs acting on the renin-angiotensin system (HR 0.92, 95% CI 0.89-0.95), corticosteroids for systemic use (0.88, 95% CI 0.84-0.93), and vaccines (0.89, 95% CI 0.82-0.96) were associated with a decreased risk of PD even up to 10 years before PD onset. Drug classes used to treat symptoms related to prodromal signs of PD, such as constipation, urological issues, and depression, were associated with an increased risk of subsequent diagnosis of PD with HRs of 1.6 (95% CI 1.49-1.73), 1.48 (1.42-1.53), and 1.94 (1.87-2.01), respectively. DISCUSSION: This drug-wide study identified 31 drug classes that were associated with the PD risk change. It reveals the links of renin-angiotensin system medications, vaccines, and corticosteroids with PD risk and suggests that monitoring drug usage using pharmacoepidemiology may allow identifying individuals with prodromal PD.

Humoral response to Epstein-Barr virus in patients with multiple sclerosis treated with B cell depletion therapy.

BACKGROUND: B cell depletion therapy is highly effective in relapsing-remitting multiple sclerosis (RRMS). However, the precise underlying mechanisms of action for its biological effects in MS have still not been clarified. Epstein-Barr virus (EBV) is a known risk factor for MS and seems to be a prerequisite for disease development. EBV resides latently in the memory B cells, and may not only increase the risk of developing MS, but also contribute to disease activity and disability progression. Therefore, the effects of B cell depletion in MS could be associated with the depletion of EBV-infected cells and the altered immune response to the virus. In this study, we investigate the impact of B cell depletion on the humoral immune response specific to EBV in patients with MS. METHODS: Newly diagnosed, treatment-naïve patients with RRMS were followed up to 18 months after initiation of B-cell depletion therapy in the Overlord-MS study, a phase III trial (NCT04578639). We analyzed serum sampled before treatment and after 3, 6, 12 and 18 months for immunoglobulin γ (IgG) against Epstein-Barr nuclear antigen 1 (EBNA1) and Epstein-Barr viral capsid antigen (VCA). We analyzed antibodies to cytomegalovirus (CMV) and total IgG in serum, as controls for viral and overall humoral immunity. The risk allele, HLA-DRB1*15:01, and the protective allele, HLA-A*02:01, were determined in all participants. In addition, polymerase chain reaction (PCR) for circulating EBV-DNA was performed in the first 156 samples drawn. The associations between time on B cell-depletion therapy and serum anti-EBV antibody levels were estimated using linear mixed-effects models. RESULTS: A total of 290 serum samples from 99 patients were available for analysis. After 6, 12 and 18 months, the EBNA1 IgG levels decreased by 12.7 % (95 % CI -18.8 to -6.60, p < 0.001), 12.1 % (95 % CI -19.8 to -3.7, p = 0.006) and 14.6 % (95 % CI to -25.3 to -2.4, p = 0.02) respectively, compared to baseline level. Carriers of the HLA-DRB1*15:01 allele had higher EBNA1 IgG levels at baseline (p = 0.02). The VCA IgG levels significantly increased by 13.7 % (95 % CI 9.4 to 18.1, p < 0.001) after 3 months, compared to baseline, and persisted at this level throughout the follow-up. CMV IgG levels decreased, but to a lesser extent than the decrease of EBNA1 IgG, and total IgG levels decreased during therapy. Circulating EBV-DNA was found in only three of 156 samples from 64 patients. CONCLUSIONS: EBNA1 IgG levels decreased, while VCA IgG levels increased, during B cell depletion therapy. This supports the hypothesis that the mechanism of action for B cell depletion therapy might be mediated by effects on EBV infection, which, in turn, mitigate immune cross-reactivity and disease perpetuation.

Childbirth delivery mode and the risk of multiple sclerosis: a prospective population-based study.

BACKGROUND: Caesarean section (CS) may affect the risk of developing multiple sclerosis (MS) in the offspring, possibly through changes in gut microbiota composition, but findings from previous studies are inconsistent. We investigated whether birth by CS was associated with the risk of adult-onset MS. METHODS: We conducted a prospective population-based cohort study, including all individuals born in Norway between 1967 and 2003, using the Medical Birth Registry of Norway linked with the Norwegian Multiple Sclerosis Registry and Biobank. The follow-up was until 2021. We used multivariable Cox models to estimate HRs for MS risk with 95% CIs. RESULTS: Among 2 046 637 individuals in the cohort, 4954 MS cases were identified. Being born by CS was associated with a modest increase in MS risk (HR=1.18, 95% CI 1.05 to 1.32). In the sibling-matched analysis, we found no association between CS and MS risk. We found an interaction between CS and gestational age (p=0.03): CS was associated with an increased risk of MS in individuals born preterm (HR=1.62, 95% CI 1.18 to 2.24), whereas there was no association in individuals born at term (HR=1.13, 95% CI 0.99 to 1.27). In a subgroup analysis of individuals born in 1988 and onwards, emergency CS was related to an elevated MS risk (HR=1.40, 95% CI 1.07 to 1.83), whereas planned CS was not (HR: 1.10, 95% CI 0.77 to 1.58). CONCLUSIONS: CS was associated with a modestly higher risk of developing MS. However, the stronger associations seen in subgroups who likely experienced a more complicated pregnancy/delivery may point to confounding underlying these associations.

Metagenomics of the Gut Microbiome in Parkinson's Disease: Prodromal Changes.

OBJECTIVE: Prior studies on the gut microbiome in Parkinson's disease (PD) have yielded conflicting results, and few studies have focused on prodromal (premotor) PD or used shotgun metagenomic profiling to assess microbial functional potential. We conducted a nested case-control study within 2 large epidemiological cohorts to examine the role of the gut microbiome in PD. METHODS: We profiled the fecal metagenomes of 420 participants in the Nurses' Health Study and the Health Professionals Follow-up Study with recent onset PD (N = 75), with features of prodromal PD (N = 101), controls with constipation (N = 113), and healthy controls (N = 131) to identify microbial taxonomic and functional features associated with PD and features suggestive of prodromal PD. Omnibus and feature-wise analyses identified bacterial species and pathways associated with prodromal and recently onset PD. RESULTS: We observed depletion of several strict anaerobes associated with reduced inflammation among participants with PD or features of prodromal PD. A microbiome-based classifier had moderate accuracy (area under the curve [AUC] = 0.76 for species and 0.74 for pathways) to discriminate between recently onset PD cases and controls. These taxonomic shifts corresponded with functional shifts indicative of carbohydrate source preference. Similar, but less marked, changes were observed in participants with features of prodromal PD, in both microbial features and functions. INTERPRETATION: PD and features of prodromal PD were associated with similar changes in the gut microbiome. These findings suggest that changes in the microbiome could represent novel biomarkers for the earliest phases of PD. ANN NEUROL 2023;94:486-501.

Subjective Cognitive Decline in Women with Features Suggestive of Prodromal Parkinson's Disease.

BACKGROUND: Cognitive deficits can be present in the prodromal phase of Parkinson's disease (PD). Subjective cognitive decline (SCD) may contribute to identifying individuals with prodromal PD. OBJECTIVE: The objective of this study was to examine whether SCD is more likely to be present in women with features suggestive of prodromal PD compared with women without these features. METHODS: The study population comprised 12,427 women from the Nurses' Health Study selected to investigate prodromal PD. Prodromal and risk markers of PD were assessed via self-administered questionnaires. We evaluated the association of hyposmia, constipation, and probable rapid eye movement sleep behavior disorder, three major features of prodromal PD, with SCD, adjusting for age, education, body mass index, physical activity, smoking, alcohol, caffeine intake, and depression. We also explored whether SCD was associated with the probability of prodromal PD and conducted additional analyses using data from neurocognitive tests. RESULTS: Women experiencing the three examined nonmotor features had the worst mean SCD score and the highest odds of poor subjective cognition (odds ratio [OR] = 1.78; 95% confidence interval [CI], 1.29-2.47). This association persisted when women with objective cognitive deficits were excluded from analyses. SCD was also more common in women with a probability of prodromal PD ≥0.80, particularly among those aged younger than 75 years (OR of poor subjective cognition = 6.57 [95% CI, 2.43-17.77]). These observations were consistent with the results from analyses using neurocognitive tests, where a worse global cognitive performance was observed among women with three features. CONCLUSIONS: Our study suggests that self-perceived cognitive decline can be present during the prodromal phase of PD. © 2023 International Parkinson and Movement Disorder Society.

Association of Polyunsaturated Fatty Acids and Clinical Progression in Patients With ALS: Post Hoc Analysis of the EMPOWER Trial.

BACKGROUND AND OBJECTIVES: Polyunsaturated fatty acids (PUFAs) have neuroprotective and anti-inflammatory effects and could be beneficial in amyotrophic lateral sclerosis (ALS). Higher dietary intake and plasma levels of PUFAs, in particular alpha-linolenic acid (ALA), have been associated with a lower risk of ALS in large epidemiologic cohort studies, but data on disease progression in patients with ALS are sparse. We examined whether plasma levels of ALA and other PUFAs contributed to predicting survival time and functional decline in patients with ALS. METHODS: We conducted a study among participants in the EMPOWER clinical trial who had plasma samples collected at the time of randomization that were available for fatty acid analyses. Plasma fatty acids were measured using gas chromatography. We used Cox proportional hazards models and linear regression to evaluate the association of individual fatty acids with risk of death and joint rank test score of functional decline and survival. RESULTS: Fatty acid analyses were conducted in 449 participants. The mean (SD) age of these participants at baseline was 57.5 (10.7) years, and 293 (65.3%) were men; 126 (28.1%) died during follow-up. Higher ALA levels were associated with lower risk of death (age-adjusted and sex-adjusted hazard ratio comparing highest vs lowest quartile 0.50, 95% CI 0.29-0.86, p-trend = 0.041) and higher joint rank test score (difference in score according to 1 SD increase 10.7, 95% CI 0.2-21.1, p = 0.045), consistent with a slower functional decline. The estimates remained similar in analyses adjusted for body mass index, race/ethnicity, symptom duration, site of onset, riluzole use, family history of ALS, predicted upright slow vital capacity, and treatment group. Higher levels of the n-3 fatty acid eicosapentaenoic acid and the n-6 fatty acid linoleic acid were associated with a lower risk of death during follow-up. DISCUSSION: Higher levels of ALA were associated with longer survival and slower functional decline in patients with ALS. These results suggest that ALA may have a favorable effect on disease progression in patients with ALS.

Beta2-adrenoreceptor agonists and long-term risk of Parkinson's disease.

INTRODUCTION: There is limited information on how the association between Parkinson's disease and the use of beta2-adrenoreceptor (ß2AR) agonists varies among groups of short-, long-, and ultra-long-acting ß2AR agonists (SABA, LABA and ultraLABA). METHODS: In this prospective study of the Norwegian population, we estimated the incidence of Parkinson's disease according to exposure to ß2AR agonists as a time-dependent variable by means of Cox regression. We adjusted for educational level, comorbidity and performed a sensitivity analysis excluding individuals with chronic obstructive pulmonary disease (COPD), all factors associated with smoking. Anticholinergics and corticosteroids as drugs with the same indication were analyzed for comparison. RESULTS: In the follow-up period from 2005 to 2019, 15,807 incident Parkinson's cases were identified. After adjustments for sex, education and age as the timescale, SABA (Hazard ratio (HR) = 0.84; 95%CI: 0.79, 0.89; p < 0.001), LABA (HR = 0.85; 95%CI: 0.81, 0.90; p < 0.001) and ultraLABA (HR = 0.6; 95%CI: 0.49, 0.73; p < 0.001) were all associated with a lower risk of Parkinson's disease. After exclusion of COPD patients, corticosteroids and anticholinergics were no longer inversely associated, whereas ß2AR agonists remained associated. CONCLUSION: Of drugs with the same indication of use, only ß2AR agonists remained inversely associated with PD risk after all adjustments, with ultraLABA displaying the overall strongest association. Although the precision of the estimate is limited by the modest number of exposed PD cases without COPD, the association is intriguing and suggest that longer-acting, more lipophilic, and thus likely more brain-penetrant ß2AR agonists could be prioritized for further studies.

Long-Term Intake of Folate, Vitamin B6, and Vitamin B12 and the Incidence of Parkinson's Disease in a Sample of U.S. Women and Men.

BACKGROUND: Folate and vitamins B6 and B12 have been proposed as protective against the development of Parkinson's disease (PD). Two prior longitudinal studies were inconclusive. OBJECTIVE: The aim was to examine the association of long-term intake of folate, vitamin B6, and vitamin B12 with the incidence of PD. METHODS: The study population comprised 80,965 women (Nurses' Health Study, 1984-2016) and 48,837 men (Health Professionals Follow-up Study, 1986-2016) followed prospectively for the development of PD. Intake of B vitamins was measured at baseline and every 4 years thereafter using food frequency questionnaires. We estimated the hazard ratio (HR) and 95% confidence interval (CI) of PD based on quintiles of cumulative average intake adjusting for potential confounders. Secondary analyses considered different lagged exposure periods as well as baseline and recent intakes. RESULTS: In separate analyses of cumulative average intake, total folate, B6, and B12 were not associated with the risk of PD. Results from 8-, 12-, and 16-year lag analyses were consistent with these findings. Results for baseline intake of folate and B6 also pointed toward a null association. In contrast, a lower PD risk was observed among individuals with higher baseline total intake of B12 (pooled HR top vs. bottom quintile: 0.80; 95% CI: 0.67-0.95; P-trend = 0.01); results from 20-year lag analyses were consistent with this finding. CONCLUSIONS: Our results do not support the hypothesis that a higher intake of folate or vitamin B6 would reduce PD risk in this population. Our results provide moderate support for a possible protective effect of vitamin B12 on the development of PD. © 2023 International Parkinson and Movement Disorder Society.

Epstein-Barr virus as a leading cause of multiple sclerosis: mechanisms and implications.

Epidemiological studies have provided compelling evidence that multiple sclerosis (MS) is a rare complication of infection with the Epstein-Barr virus (EBV), a herpesvirus that infects more than 90% of the global population. This link was long suspected because the risk of MS increases markedly after infectious mononucleosis (symptomatic primary EBV infection) and with high titres of antibodies to specific EBV antigens. However, it was not until 2022 that a longitudinal study demonstrated that MS risk is minimal in individuals who are not infected with EBV and that it increases over 30-fold following EBV infection. Over the past few years, a number of studies have provided clues on the underlying mechanisms, which might help us to develop more targeted treatments for MS. In this Review, we discuss the evidence linking EBV to the development of MS and the mechanisms by which the virus is thought to cause the disease. Furthermore, we discuss implications for the treatment and prevention of MS, including the use of antivirals and vaccines.

Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system of unknown etiology. We tested the hypothesis that MS is caused by Epstein-Barr virus (EBV) in a cohort comprising more than 10 million young adults on active duty in the US military, 955 of whom were diagnosed with MS during their period of service. Risk of MS increased 32-fold after infection with EBV but was not increased after infection with other viruses, including the similarly transmitted cytomegalovirus. Serum levels of neurofilament light chain, a biomarker of neuroaxonal degeneration, increased only after EBV seroconversion. These findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS.

Intake of carbohydrates and SFA and risk of CHD in middle-age adults: the Hordaland Health Study (HUSK).

OBJECTIVE: Limiting SFA intake may minimise the risk of CHD. However, such reduction often leads to increased intake of carbohydrates. We aimed to evaluate associations and the interplay of carbohydrate and SFA intake on CHD risk. DESIGN: Prospective cohort study. SETTING: We followed participants in the Hordaland Health Study, Norway from 1997-1999 through 2009. Information on carbohydrate and SFA intake was obtained from a FFQ and analysed as continuous and categorical (quartiles) variables. Multivariable Cox regression estimated hazard ratios (HR) and 95 % CI. Theoretical substitution analyses modelled the substitution of carbohydrates with other nutrients. CHD was defined as fatal or non-fatal CHD (ICD9 codes 410-414 and ICD10 codes I20-I25). PARTICIPANTS: 2995 men and women, aged 46-49 years. RESULTS: Adjusting for age, sex, energy intake, physical activity and smoking, SFA was associated with lower risk (HRQ4 v. Q1 0·44, 95 % CI 0·26, 0·76, Ptrend = 0·002). For carbohydrates, the opposite pattern was observed (HRQ4 v. Q1 2·10, 95 % CI 1·22, 3·63, Ptrend = 0·003). SFA from cheese was associated with lower CHD risk (HRQ4 v. Q1 0·44, 95 % CI 0·24, 0·83, Ptrend = 0·006), while there were no associations between SFA from other food items and CHD. A 5 E% substitution of carbohydrates with total fat, but not SFA, was associated with lower CHD risk (HR 0·75, 95 % CI 0·62, 0·90). CONCLUSIONS: Higher intake of predominantly high glycaemic carbohydrates and lower intake of SFA, specifically lower intake from cheese, were associated with higher CHD risk. Substituting carbohydrates with total fat, but not SFA, was associated with significantly lower risk of CHD.