Although genetic susceptibility explains the clustering of multiple sclerosis (MS) cases within families, the changes in MS risk that occur with migration can be explained only by changes in the ...environment. The strongest known risk factor for MS is infection with Epstein-Barr virus (EBV). Compared with uninfected individuals, the hazard of developing MS is approximately 15-fold higher among individuals infected with EBV in childhood and about 30-fold higher among those infected with EBV in adolescence or later in life. Although the mechanisms underlying this association remain unclear, the data provide strong evidence of a causal relation between EBV infection and MS risk. Relevant aspects of MS epidemiology beyond genetics are not explained by EBV involvement, however, implying the involvement of other factors. Modifiable factors for MS risk include smoking and childhood obesity. Increased risk of MS in individuals with vitamin D insufficiency has been proposed to explain the strong latitude gradient in MS prevalence. Results of case-control studies that relied on prevalent MS cases have been mixed, however, and potentially influenced by selection and recall biases. In a recent case-control study of individuals presenting with a first demyelinating episode, higher levels of vitamin D, sun exposure or actinic damage were found to be associated with reduced MS risk. Two longitudinal studies have thus far been completed. In the first, based on assessment of vitamin D intake from diet and supplements, the risk of MS was found to be 30% lower among women in the highest quintile compared with those in the lowest quintile. In the second study, conducted among young adults in the US military, vitamin D status was assessed by averaging multiple season-adjusted measures of 25-hydroxyvitamin D (25OHD). During an average of 5 years' follow-up, MS risk among healthy young adults with serum levels of 25(OH) vitamin D >100 nmol/l was about 60% lower than in individuals of the same age and sex with serum 25(OH) vitamin D levels <100 nmol/l. If confirmed, these findings suggest that a high proportion of MS cases could be effectively prevented by vitamin D supplementation. Furthermore, there is growing evidence that vitamin D insufficiency is a risk factor for conversion from clinically isolated syndrome to MS and for MS progression. Both prevention and treatment trials with vitamin D are needed to confirm these findings and to determine optimal levels of vitamin D.
Summary Since 2006, several longitudinal studies have assessed environmental or behavioural factors that seem to modify the risk of developing Parkinson's disease. Increased risk of Parkinson's ...disease has been associated with exposure to pesticides, consumption of dairy products, history of melanoma, and traumatic brain injury, whereas a reduced risk has been reported in association with smoking, caffeine consumption, higher serum urate concentrations, physical activity, and use of ibuprofen and other common medications. Randomised trials are investigating the possibility that some of the negative risk factors might be neuroprotective and thus beneficial in individuals with early Parkinson's disease, particularly with respect to smoking (nicotine), caffeine, and urate. In the future, it might be possible to identify Parkinson's disease in its prodromal phase and to promote neuroprotective interventions before the onset of motor symptoms. At this time, however, the only intervention that seems justifiable for the primary prevention of Parkinson's disease is the promotion of physical activity, which is likely to be beneficial for the prevention of several chronic diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Although genetic susceptibility explains the clustering of multiple sclerosis (MS) cases within families and the sharp decline in risk with increasing genetic distance, it cannot fully explain the ...geographic variations in MS frequency and the changes in risk that occur with migration. Epidemiological data provide some support for the “hygiene hypothesis,” but with the additional proviso for a key role of Epstein–Barr virus (EBV) in determining MS risk. We show that whereas EBV stands out as the only infectious agent that can explain many of the key features of MS epidemiology, by itself the link between EBV and MS cannot explain the decline in risk among migrants from high to low MS prevalence areas. This decline implies that either EBV strains in low‐risk areas have less propensity to cause MS, or that other infectious or noninfectious factors modify the host response to EBV or otherwise contribute to determine MS risk. The role of infectious factors is discussed here; in a companion article, we will examine the possible role of noninfectious factors and provide evidence that high levels of vitamin D may have a protective role, particularly during adolescence. The primary purpose of these reviews is to identify clues to the causes of MS and to evaluate the possibility of primary prevention. Ann Neurol 2007;61:288–299
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Oxidative stress has been implicated as a core contributor to the initiation and progression of multiple neurological diseases. Genetic and environmental factors can produce oxidative stress through ...mitochondrial dysfunction leading to the degeneration of dopaminergic and other neurons underlying Parkinson disease (PD). Although clinical trials of antioxidants have thus far failed to demonstrate slowed progression of PD, oxidative stress remains a compelling target. Rather than prompting abandonment of antioxidant strategies, these failures have raised the bar for justifying drug and dosing selections and for improving study designs to test for disease modification by antioxidants. Urate, the main antioxidant found in plasma as well as the end product of purine metabolism in humans, has emerged as a promising potential neuroprotectant with advantages that distinguish it from previously tested antioxidant agents. Uniquely, higher urate levels in plasma or cerebrospinal fluid (CSF) have been linked to both a lower risk of developing PD and to a slower rate of its subsequent progression in numerous large prospective epidemiological and clinical cohorts. Laboratory evidence that urate confers neuroprotection in cellular and animal models of PD, possibly via the Nrf2 antioxidant response pathway, further strengthened its candidacy for rapid clinical translation. An early phase trial of the urate precursor inosine demonstrated its capacity to safely produce well tolerated, long-term elevation of plasma and CSF urate in early PD, supporting a phase 3 trial now underway to determine whether oral inosine dosed to elevate urate to concentrations predictive of favorable prognosis in PD slows clinical decline in people with recently diagnosed, dopamine transporter-deficient PD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
To examine whether obesity during childhood, adolescence, or adulthood is associated with an increased risk of multiple sclerosis (MS).
Women in the Nurses' Health Study (n = 121,700) and Nurses' ...Health Study II (n = 116,671) provided information on weight at age 18 and weight and height at baseline, from which body mass index was derived. Women also selected silhouettes representing their body size at ages 5, 10, and 20. Over the total 40 years of follow-up in both cohorts combined, we confirmed 593 cases of MS. Cox proportional hazards models, adjusting for age, latitude of residence, ethnicity, and cigarette smoking, were used to estimate the rate ratios and 95% confidence intervals (CI).
Obesity at age 18 (body mass index > or =30 kg/m(2)) was associated with a greater than twofold increased risk of MS (multivariate relative risk(pooled) = 2.25, 95% CI: 1.50-3.37, p trend <0.001). After adjusting for body size at age 20, having a large body size at ages 5 or 10 was not associated with risk of MS, whereas a large body size at age 20 was associated with a 96% increased risk of MS (95% CI: 1.33-2.89, p trend = 0.009). No significant association was found between adult body mass and MS risk.
Obese adolescents have an increased risk of developing multiple sclerosis (MS). Although the mechanisms of this association remain uncertain, this result suggests that prevention of adolescent obesity may contribute to reduced MS risk.
Vitamin D and multiple sclerosis Ascherio, Alberto, Prof; Munger, Kassandra L, ScD; Simon, K Claire, ScD
Lancet neurology,
06/2010, Volume:
9, Issue:
6
Journal Article
Peer reviewed
Summary The hypothesis that adequate vitamin D nutrition can contribute to the prevention of multiple sclerosis (MS) was originally proposed to explain the geographical distribution of MS, but only ...recently has the relation between various measures of vitamin D (eg, sun exposure, dietary sources, and serum concentrations of 25-hydroxyvitamin D) and risk of developing MS been rigorously investigated. Overall, the results of these studies support a protective effect of vitamin D, but there are uncertainties and many unanswered questions, including how vitamin D exerts a protective effect, how genetic variations modify the effect, and whether vitamin D can influence the course of MS progression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Although strong genetic determinants of multiple sclerosis (MS) exist, the findings of migration studies support a role for environmental factors in this disease. Through rigorous epidemiological ...investigation, Epstein-Barr virus infection, vitamin D nutrition and cigarette smoking have been identified as likely causal factors in MS. In this Review, the strength of this evidence is discussed, as well as the potential biological mechanisms underlying the associations between MS and environmental, lifestyle and dietary factors. Both vitamin D nutrition and cigarette smoking are modifiable; as such, increasing vitamin D levels and smoking avoidance have the potential to substantially reduce MS risk and influence disease progression. Improving our understanding of the environmental factors involved in MS will lead to new and more-effective approaches to prevent this disease.
Neuroinflammation may contribute to the pathogenesis of Parkinson disease (PD). Use of nonsteroidal anti-inflammatory drugs (NSAID) in general, and possibly ibuprofen in particular, has been shown to ...be related to lower PD risk in previous epidemiologic studies.
We prospectively examined whether use of ibuprofen or other NSAIDs is associated with lower PD risk among 136,197 participants in the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) free of PD at baseline (1998 for NHS and 2000 for HPFS). NSAIDs use was assessed via questionnaire. Results were combined in a meta-analysis with those of published prospective investigations.
We identified 291 incident PD cases during 6 years of follow-up. Users of ibuprofen had a significantly lower PD risk than nonusers (relative risk RR, adjusted for age, smoking, caffeine, and other covariates = 0.62; 95% confidence interval CI 0.42-0.93; p = 0.02). There was a dose-response relationship between tablets of ibuprofen taken per week and PD risk (p trend = 0.01). In contrast, PD risk was not significantly related to use of aspirin (RR = 0.99; 95% CI 0.78-1.26), other NSAIDs (RR = 1.26; 95% CI 0.86-1.84), or acetaminophen (RR = 0.86; 95% CI 0.62-1.18). Similar results were obtained in the meta-analyses: the pooled RR was 0.73 (95% CI 0.63-0.85; p < 0.0001) for ibuprofen use, whereas use of other types of analgesics was not associated with lower PD risk.
The association between use of ibuprofen and lower PD risks, not shared by other NSAIDs or acetaminophen, suggests ibuprofen should be further investigated as a potential neuroprotective agent against PD.
OBJECTIVE:To examine whether higher plasma urate concentrations are associated with a lower risk of developing Parkinson disease (PD) and whether there is a sex difference in the potential urate–PD ...relationship.
METHODS:We conducted a nested case-control study based on 90,214 participants of 3 ongoing US cohorts. We identified 388 new PD cases (202 men and 186 women) since blood collection, which were then matched to 1,267 controls. PD cases were confirmed by medical record review. Conditional logistic regression estimated relative risks (RRs) and 95% confidence intervals (95% CIs), after adjustment for age, smoking, caffeine intake, plasma concentrations of cholesterol and ferritin, and other covariates. We also conducted a meta-analysis to combine our study with 3 previously published prospective studies on urate and PD risk.
RESULTS:In the present nested case-control study, the multivariate-adjusted RRs of PD comparing extreme quartiles of urate were 0.63 (95% CI 0.35, 1.10; ptrend = 0.049) in men and 1.04 (95% CI 0.61, 1.78; ptrend = 0.44) in women (pheterogeneity = 0.001). In the meta-analysis, the pooled RRs comparing 2 extreme quartiles of urate were 0.63 (95% CI 0.42, 0.95) in men and 0.89 (95% CI 0.57, 1.40) in women.
CONCLUSION:We observed that men, but not women, with higher urate concentrations had a lower future risk of developing PD, suggesting that urate could be protective against PD risk or could slow disease progression during the preclinical stage of disease.
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