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This cohort study investigates the association of the Mediterranean–Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND) diet with risk of dementia. Key Points: Question: Is adherence to the Mediterranean–Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND) diet associated with the risk of dementia? Findings: In this investigation of 3 prospective cohort studies including 18 136 participants and a meta-analysis including 224 049 participants, adherence to the MIND diet was associated with a lower risk of incident dementia in middle-aged and older adults. The highest adherence was associated with approximately 17% lower risk of dementia compared with the lowest adherence. Meaning: The MIND diet may potentially reduce dementia risk, but further investigations are needed in different populations. Importance: Dementia threatens the well-being of older adults, making efforts toward prevention of great importance. Objective: To evaluate the association of the Mediterranean–Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND) diet with the risk of dementia in 3 prospective studies and a meta-analysis. Design, Setting, and Participants: Cohort analyses included the Whitehall II study (WII), the Health and Retirement Study (HRS), and the Framingham Heart Study Offspring cohort (FOS), and the meta-analysis included 11 cohort studies. Participants were middle-aged and older women and men from WII in 2002 to 2004, HRS in 2013, and FOS in 1998 to 2001 without dementia at the study baseline. Data were analyzed from May 25 to September 1, 2022. Exposures: MIND diet score was measured using food frequency questionnaires, and scores ranged from 0 to 15, with a higher score indicating higher adherence to the MIND diet. Main Outcome and Measures: Incident all-cause dementia, with cohort-specific definitions. Results: Included in this study were 8358 participants (mean [SD] age, 62.2 [6.0] years; 5777 male [69.1%]) from WII, 6758 participants (mean [SD] age, 66.5 [10.4] years; 3965 female [58.7%]) from HRS, and 3020 participants (mean [SD] age, 64.2 [9.1] years; 1648 female [54.6%]) from FOS. The mean (SD) baseline MIND diet score was 8.3 (1.4) in WII, 7.1 (1.9) in HRS, and 8.1 (1.6) in FOS. Over 166 516 person-years, a total of 775 participants (220 in WII, 338 in HRS, and 217 in FOS) developed incident dementia. In the multivariable-adjusted Cox proportional hazard model, higher MIND diet score was associated with lower risk of dementia (pooled hazard ratio [HR] for every 3-point increment, 0.83; 95% CI, 0.72-0.95; P for trend =.01; I2 = 0%). The associations were consistently observed in subgroups defined by sex, age, smoking status, and body mass index. In the meta-analysis of 11 cohort studies with 224 049 participants (5279 incident dementia cases), the highest tertile of MIND diet score was associated with lower risk of dementia compared with the lowest tertile (pooled HR, 0.83; 95% CI, 0.76-0.90; I2 = 35%). Conclusions and Relevance: Results suggest that adherence to the MIND diet was associated with lower risk of incident dementia in middle-aged and older adults. Further studies are warranted to develop and refine the specific MIND diet for different populations. [ABSTRACT FROM AUTHOR]

A prospective study investigates whether levels of 25-hydroxyvitamin D, a good marker of vitamin D availability to tissues, are associated with risk of multiple sclerosis (MS). Results suggest that high serum levels of 25-hydroxyvitamin D are associated with a lower risk of multiple sclerosis.

A study is conducted to determine whether antibodies to Epstein-Barr virus (EBV) are elevated before the onset of multiple sclerosis (MS). The results suggest an age-dependent relationship between EBV infection and development of MS.

Exposure to Epstein-Barr virus may be a risk factor for multiple sclerosis (MS), according to a study of 83 military personnel who developed MS and 166 who did not. Blood samples taken several years before showed that increased antibody levels against Epstein-Barr virus was a risk factor for the future development of MS. There was no association between cytomegalovirus and MS.

Men who eat fish at least once a month can lower their risk of a stroke by 40%, according to a 12-year study of 43,671 men. Eating fish more frequently did not substantially lower the risk any more than 50%. Most strokes are caused by a blood clot in the brain that cuts off the blood supply to various parts of the brain. Fish consumption did not reduce the risk of a hemorrhagic stroke, which is caused by bleeding inside the brain.

Epstein-Barr virus infection may increase a person's risk of developing multiple sclerosis, according to a study of 144 women with multiple sclerosis and 288 healthy women. Epstein-Barr virus causes mononucleosis., Context: Epidemiological studies suggest an association between infection with Epstein-Barr virus (EBV) and risk of multiple sclerosis (MS). Objective: To determine whether elevation in serum antibody titers to EBV viral capsid antigen (VCA), nuclear antigens (EBNA, EBNA-1, and EBNA-2) and diffuse and restricted early antigen (EA-D and EA-R) as well as to cytomegalovirus (CMV) precede the occurrence of MS. Design Setting, and Subjects: Prospective, nested case-control study. Of 62439 women participating in the Nurses' Health Study (aged 30-55 years in 1976) and Nurses' Health Study II (aged 25-42 years in 1989) who gave blood samples in 19891990 and 1996-1999, respectively, and were followed up through 1999, 144 women with definite or probable MS and 288 healthy age-matched controls were included in the analysis. Main Outcome Measure: Serum antibody titers to the specific EBV and CMV antigens, compared between cases and controls. Results: We documented 18 cases of MS with blood collected before disease onset. Compared with their matched controls, these women had higher serum geometric mean titers (GMTs) of antibodies to EBV but not CMV. Elevations were significant for antibodies to EBNA-1 (GMT, 515 vs 203; P=.03), EBNA-2 (GMT, 91 vs 40; P=.01), and EA-D (15.9 vs 5.9; P=.04). The strongest association was found for antibodies to EBNA-2; a 4-fold difference in titers was associated with a relative risk (RR) of MS of 3.9 (95% confidence interval [CI], 1.1-13.7). The corresponding RRs were 1.6 (95% CI, 0.73.7) for VCA, 2.5 (95% CI, 1.0-6.3) for EBNA, 1.8(95% CI, 1.0-3.1) for EA-D, and 1.0 (95% CI, 0.6-1.7) for CMV. Significant but generally weaker elevations in anti-EBV antibodies were also found in analyses of 126 cases of MS with blood collected after disease onset and their matched controls. Conclusions: Our results support a role of EBV in the etiology of MS.

A high-fiber diet may reduce the risk of coronary heart disease. Researchers analyzed data from 43,757 men in the Health Professionals Follow-up Study who were asked to fill out dietary questionnaires in 1986, 1988, 1990, and 1992. The questionnaire surveyed how often the men ate 131 different foods. During the six-year follow-up, 734 men had a heart attack or died from coronary heart disease. Men who ate the most fiber had approximately two-thirds of the risk of having a fatal or nonfatal coronary event as men who ate the least fiber. Only cereal fiber was statistically significant in reducing the risk of a coronary event. Adjustment for beta carotene, folate and vitamin B6 intake moderated the protective effect of fruit and vegetable fiber, but the protective effect of cereal fiber remained strong.

Importance: Urate elevation, despite associations with crystallopathic, cardiovascular, and metabolic disorders, has been pursued as a potential disease-modifying strategy for Parkinson disease (PD) based on convergent biological, epidemiological, and clinical data.Objective: To determine whether sustained urate-elevating treatment with the urate precursor inosine slows early PD progression.Design, Participants, and Setting: Randomized, double-blind, placebo-controlled, phase 3 trial of oral inosine treatment in early PD. A total of 587 individuals consented, and 298 with PD not yet requiring dopaminergic medication, striatal dopamine transporter deficiency, and serum urate below the population median concentration (<5.8 mg/dL) were randomized between August 2016 and December 2017 at 58 US sites, and were followed up through June 2019.Interventions: Inosine, dosed by blinded titration to increase serum urate concentrations to 7.1-8.0 mg/dL (n = 149) or matching placebo (n = 149) for up to 2 years.Main Outcomes and Measures: The primary outcome was rate of change in the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS; parts I-III) total score (range, 0-236; higher scores indicate greater disability; minimum clinically important difference of 6.3 points) prior to dopaminergic drug therapy initiation. Secondary outcomes included serum urate to measure target engagement, adverse events to measure safety, and 29 efficacy measures of disability, quality of life, cognition, mood, autonomic function, and striatal dopamine transporter binding as a biomarker of neuronal integrity.Results: Based on a prespecified interim futility analysis, the study closed early, with 273 (92%) of the randomized participants (49% women; mean age, 63 years) completing the study. Clinical progression rates were not significantly different between participants randomized to inosine (MDS-UPDRS score, 11.1 [95% CI, 9.7-12.6] points per year) and placebo (MDS-UPDRS score, 9.9 [95% CI, 8.4-11.3] points per year; difference, 1.26 [95% CI, -0.59 to 3.11] points per year; P = .18). Sustained elevation of serum urate by 2.03 mg/dL (from a baseline level of 4.6 mg/dL; 44% increase) occurred in the inosine group vs a 0.01-mg/dL change in serum urate in the placebo group (difference, 2.02 mg/dL [95% CI, 1.85-2.19 mg/dL]; P<.001). There were no significant differences for secondary efficacy outcomes including dopamine transporter binding loss. Participants randomized to inosine, compared with placebo, experienced fewer serious adverse events (7.4 vs 13.1 per 100 patient-years) but more kidney stones (7.0 vs 1.4 stones per 100 patient-years).Conclusions and Relevance: Among patients recently diagnosed as having PD, treatment with inosine, compared with placebo, did not result in a significant difference in the rate of clinical disease progression. The findings do not support the use of inosine as a treatment for early PD.Trial Registration: ClinicalTrials.gov Identifier: NCT02642393. [ABSTRACT FROM AUTHOR]

Men who have undergone a vasectomy may have a higher risk of developing prostate cancer than those who have not. Prostate cancer is the second most common cause of cancer-associated deaths among men. Among 25,340 men studied through surveys completed by their wives, 13,034 had undergone a vasectomy and 12,306 had not undergone a vasectomy by 1976. Ninety-six of these men were diagnosed with prostate cancer between 1976 and 1989. Men who had undergone a vasectomy had a significantly higher risk of prostate cancer than those who were had not had a vasectomy. The risk of prostate cancer was significantly higher in men who had had their vasectomy before 1956 than in those whose vasectomy was more recent. A vasectomy may decrease the secretion of various substances by the prostate gland, and does lower the volume of seminal plasma. These changes in prostate gland function may increase the risk of prostate cancer.

Men who have had a vasectomy may have a higher risk of developing prostate cancer than those who have not. Prostate cancer is the second most common cause of cancer-associated deaths among men. Among 47,855 primarily white men between 40 and 75 years old, 10,055 had had a vasectomy and 37,800 had not had a vasectomy by 1986. Three hundred of these men were diagnosed with prostate cancer between 1986 and 1990. The risk of prostate cancer was higher among men who had had a vasectomy than among those who had not. The risk of prostate cancer was significantly higher in men who had had a vasectomy before 1965 (22 years before the study) than in those whose vasectomy was more recent. Men who have undergone a vasectomy secrete lower amounts of various substances from the prostate gland. This change in prostate gland function may increase the risk of prostate cancer.

Eating fruits and vegetables may lower the risk of stroke. Researchers analyzed the link diet and stroke in 75,596 women in the Nurses' Health Study and 38,683 men in the Health Professionals' Follow-up Study. Over an 8- to 14-year period, 366 women and 204 men had a stroke. Those who ate the most fruits and vegetables every day had a 30% lower risk of having a stroke than those who ate the least. Green leafy vegetables and cruciferous vegetables such as broccoli, cabbage, cauliflower, and brussel sprouts were the most beneficial, as were citrus fruits and citrus fruit juice.

Context: Reduction in egg consumption has been widely recommended to lower blood cholesterol levels and prevent coronary heart disease (CHD). Epidemiologic studies on egg consumption and risk of CHD are sparse.Objective: To examine the association between egg consumption and risk of CHD and stroke in men and women.Design and Setting: Two prospective cohort studies, the Health Professionals Follow-up Study (1986-1994) and the Nurses' Health Study (1980-1994).Participants: A total of 37851 men aged 40 to 75 years at study outset and 80082 women aged 34 to 59 years at study outset, free of cardiovascular disease, diabetes, hypercholesterolemia, or cancer.Main Outcome Measures: Incident nonfatal myocardial infarction, fatal CHD, and stroke corresponding to daily egg consumption as determined by a food-frequency questionnaire.Results: We documented 866 incident cases of CHD and 258 incident cases of stroke in men during 8 years of follow-up and 939 incident cases of CHD and 563 incident cases of stroke in women during 14 years of follow-up. After adjustment for age, smoking, and other potential CHD risk factors, we found no evidence of an overall significant association between egg consumption and risk of CHD or stroke in either men or women. The relative risks (RRs) of CHD across categories of intake were less than 1 per week (1.0), 1 per week (1.06), 2 to 4 per week (1.12), 5 to 6 per week (0.90), and > or =1 per day (1.08) (P for trend = .75) for men; and less than 1 per week (1.0), 1 per week (0.82), 2 to 4 per week (0.99), 5 to 6 per week (0.95), and > or =1 per day (0.82) (P for trend = .95) for women. In subgroup analyses, higher egg consumption appeared to be associated with increased risk of CHD only among diabetic subjects (RR of CHD comparing more than 1 egg per day with less than 1 egg per week among diabetic men, 2.02 [95% confidence interval, 1.05-3.87; P for trend = .04], and among diabetic women, 1.49 [0.88-2.52; P for trend = .008]).Conclusions: These findings suggest that consumption of up to 1 egg per day is unlikely to have substantial overall impact on the risk of CHD or stroke among healthy men and women. The apparent increased risk of CHD associated with higher egg consumption among diabetic participants warrants further research. [ABSTRACT FROM AUTHOR]

IMPORTANCE Although autism spectrum disorder (ASD) is known to be heritable, patterns of inheritance of subclinical autistic traits in nonclinical samples are poorly understood. OBJECTIVE To examine the familiality of Social Responsiveness Scale (SRS) scores of individuals with and without ASD. DESIGN. SETTING. AND PARTICIPANTS We performed a nested case-control study (pilot study; July 1,2007, through June 30,2009; full-scale study: September 15,2008, through September 14,2012) within a population-based longitudinal cohort. Participants were drawn from the Nurses' Health Study II, a cohort of 116 430 female nurses recruited in 1989. Case participants were index children with reported ASD; control participants were frequency matched by year of birth of case participants among those not reporting ASD. Of 3161 eligible participants, 2144 nurses (67.8%) returned SRS forms for a child and at least 1 parent and were included in these analyses. EXPOSURE The SRS scores, as reported by nurse mothers and their spouses, were examined in association with risk of ASD using crude and adjusted logistic regression analyses. The SRS scores of the children were examined in association with SRS scores of the parents using crude and adjusted linear regression analyses stratified by case status. MAIN OUTCOMES AND MEASURES Autism spectrum disorder, assessed by maternal report, validated in a subgroup with the Autism Diagnostic Interview-Revised. RESULTS A total of 1649 individuals were included in these analyses, including 256 ASD case participants, 1393 control participants, 1233 mothers, and 1614 fathers. Risk of ASD was increased by 85.0% among children whose parents had concordantly elevated SRS scores (odds ratio [OR], 1.85; 95% CI, 1.08-3.16) and by 52.0% when the score of either parent was elevated (OR, 1.52; 95% CI, 1.11-2.06). Elevated scores of the father significantly increased the risk of ASD in the child (OR, 1.94; 95% CI, 1.38-2.71), but no association was seen with elevated scores of the mother. Elevated parent scores significantly increased child scores in controls, corresponding to an increase in 23 points (P < .001). CONCLUSIONS AND RELEVANCE These findings support the role of additive genetic influences in concentrating inherited ASD susceptibility in successive generations and the potential role of preferential mating, and suggest that typical variation in parental social functioning can produce clinically significant differences in offspring social traits. [ABSTRACT FROM AUTHOR]

Importance: Adverse perinatal circumstances have been associated with increased risk for autism in offspring. Women exposed to childhood abuse experience more adverse perinatal circumstances than women unexposed, but whether maternal abuse is associated with autism in offspring is unknown. Objectives: To determine whether maternal exposure to childhood abuse is associated with risk for autism in offspring and whether possible increased risk is accounted for by a higher prevalence of adverse perinatal circumstances among abused women, including toxemia, low birth weight, gestational diabetes, previous induced abortion, intimate partner abuse, pregnancy length shorter than 37 weeks, selective serotonin reuptake inhibitor use, and alcohol use and smoking during pregnancy. Design and Setting: Nurses' Health Study II, a population-based longitudinal cohort of 116 430 women. Participants: Nurses with data on maternal childhood abuse and child's autism status (97.0% were of white race/ethnicity). Controls were randomly selected from among children of women who did not report autism in offspring (participants included 451 mothers of children with autism and 52 498 mothers of children without autism). Main Outcome Measures: Autism spectrum disorder in offspring, assessed by maternal report and validated with the Autism Diagnostic Interview-Revised in a subsample. Results: Exposure to abuse was associated with increased risk for autism in children in a monotonically increasing fashion. The highest level of abuse was associated with the greatest prevalence of autism (1.8% vs 0.7% among women not abused, P = .005) and with the greatest risk for autism adjusted for demographic factors (risk ratio, 3.7; 95% CI, 2.3-5.8). All adverse perinatal circumstances except low birth weight were more prevalent among women abused in childhood. Adjusted for perinatal factors, the association of maternal childhood abuse with autism in offspring was slightly attenuated (risk ratio for highest level of abuse, 3.0; 95% CI, 1.9-4.8). Conclusions and Relevance: We identify an inter-generational association between maternal exposure to childhood abuse and risk for autism in the subsequent generation. Adverse perinatal circumstances accounted for only a small portion of this increased risk. [ABSTRACT FROM AUTHOR]

Objective: To prospectively examine whether use of statins is associated with altered risk of Parkinson disease (PD). Design, Setting, and Participants: A prospective study including 38 192 men and 90 874 women participating in 2 ongoing US cohorts, the Health Professional Follow-up Study and the Nurses' Health Study, was conducted. Information on regular cholesterol-lowering drug use (⩾2 times/wk) was collected in 1994 in both cohorts via questionnaire. Relative risks (RRs) and 95% CIs were computed using Cox proportional hazards models adjusting for age, smoking, caffeine intake, duration of hypercholesterolemia, and other covariates. Main Outcome Measure: Incident PD. Results: During 12 years of follow-up (1994-2006), we documented 644 incident PD cases (338 women and 306 men). The risk of PD was lower among current statin users (adjusted pooled RR=0.74; 95% CI, 0.54-1.00; P=.049) relative to nonusers. A significant association was observed in participants younger than 60 years at baseline (adjusted pooled RR=0.31; 95% CI, 0.11-0.86; P=.02) but not among those who were older (adjusted pooled RR=0.83; 95% CI, 0.60-1.14; P=.25) (P for interaction=. 03). Conclusions: We found that regular use of statins was associated with a modest reduction in PD risk. The possibility that some statins may reduce PD risk deserves further consideration. [ABSTRACT FROM AUTHOR]

The article discusses a study of the association between caffeine consumption or intake of caffeinated beverages and risk of depression. A total of 50,931 female registered nurses who were depression free in 1996 were involved in the study. The number of cases of clinical depression among the subjects during the 10-year follow-up from 1996 to 2006 reached 2,607. Results emphasize the role of caffeinated coffee consumption in depression risk.

Background: Cigarette smoking has been proposed as a risk factor for amyotrophic lateral sclerosis (ALS), but epidemiological studies supporting this hypothesis have been small and mostly retrospective. Objective: To prospectively examine the relation between smoking and ALS in 5 well-established large cohorts. Design: Five prospective cohorts with study-specific follow-up ranging from 7 to 28 years. Setting: Academic research. Patients: Participants in the Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort, and the National Institutes of Health-AARP (formerly known as the American Association of Retired Persons) Diet and Health Study. Main Outcome Measures: Amyotrophic lateral sclerosis deaths identified through the National Death Index. In the Nurses' Health Study and the Health Professionals Follow-up Study, confirmed nonfatal incident ALS was also included. Results: A total of 832 participants with ALS were documented among 562 804 men and 556 276 women. Smokers had a higher risk of ALS than never smokers, with age- and sex-adjusted relative risks of 1.44 (95% confidence interval, 1.23-1.68; P<.001) for former smokers and 1.42(95% confidence interval, 1.07-1.88; P=.02) for current smokers. Although the risk of ALS was positively associated with pack-years smoked (P<.001), duration of smoking (9%increase for each10years of smoking, P=.006), and the number of cigarettes smoked per day (10% increase for each increment of 10 cigarettes smoked per day, P<.001), these associations did not persist when never smokers were excluded. However, among ever smokers, the risk of ALS increased as age at smoking initiation decreased (P=.03). Conclusions: Results of this large longitudinal study support the hypothesis that cigarette smoking increases the risk of ALS. The potential importance of age at smoking initiation and the lack of a dose response deserve further investigation. [ABSTRACT FROM AUTHOR]

The article discusses research on the individual and joint effects of diabetes mellitus and depression on women mortality rate. Participants of the study by An Pan et al were 78,282 women, from 54 to 79 years old with self-reported diagnosed diabetes and depression and compared their age-adjusted relative risks (RR). Conclusions indicated the significant association of diabetes and depression on the risk of cardiovascular disease and all-cause mortality rate where women were identified at particularly high risk.

The article discusses a study which examined the bidirectional association between depression and type 2 diabetes mellitus in women. Researchers observed 65,381 women aged 50-75 years old from 1996 to 2006. Charts are given showing the women's depressive symptom status and confirmed diabetes status. To investigate the complex association between depression and type 2 diabetes, the researchers used biennially repeated measurements of the diseases along with their risk factors. The results showed that diabetes-depression association is bidirectional.

Background: The risk of Parkinson disease (PD) and its rate of progression may decline with increasing concentration of blood urate, a major antioxidant. Objective: To determine whether serum and cerebrospinal fluid concentrations of urate predict clinical progression in patients with PD. Design, Setting, and Participants: Eight hundred subjects with early PD enrolled in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial. The pretreatment urate concentration was measured in serum for 774 subjects and in cerebrospinal fluid for 713 subjects. Main Outcome Measures: Treatment-, age-, and sexadjusted hazard ratios (HRs) for clinical disability requiring levodopa therapy, the prespecified primary end point of the original DATATOP trial. Results: The HR of progressing to the primary end point decreased with increasing serum urate concentrations (HR for highest vs lowest quintile=0.64; 95% confidence interval [CI], 0.44-0.94; HR for a 1-SD increase=0.82; 95% CI, 0.73-0.93). In analyses stratified by α-tocopherol treatment (2000 IU/d), a decrease in the HR for the primary end point was seen only among subjects not treated with α-tocopherol (HR for a 1-SD increase=0.75; 95% CI, 0.62-0.89; vs HR for those treated=0.90; 95% CI, 0.75-1.08). Results were similar for the rate of change in the Unified Parkinson's Disease Rating Scale score. Cerebrospinal fluid urate concentration was also inversely related to both the primary end point (HR for highest vs lowest quintile=0.65; 95% CI, 0.44-0.96; HR for a 1-SD increase=0.89; 95% CI, 0.79-1.02) and the rate of change in the Unified Parkinson's Disease Rating Scale score. As with serum urate concentration, these associations were present only among subjects not treated with α-tocopherol. Conclusions: Higher serum and cerebrospinal fluid urate concentrations at baseline were associated with slower rates of clinical decline. The findings strengthen the link between urate concentration and PD and the rationale for considering central nervous system urate concentration elevation as a potential strategy to slow PD progression. [ABSTRACT FROM AUTHOR]

Background: Although cigarette smokers are at increased risk of developing multiple sclerosis (MS), the effect of smoking on the progression of MS remains uncertain. Objective: To establish the relationship between cigarette smoking and progression of MS using clinical and magnetic resonance imaging outcomes Design: Cross-sectional survey and longitudinal follow- up for a mean of 3.29 years, ending January 15, 2008. Setting: Partners MS Center (Boston, Massachusetts), a referral center for patients with MS. Patients: Study participants included 1465 patients with clinically definite MS (25.1% men), with mean (range) age at baseline of 42.0 (16-75) years and disease duration of 9.4 (0-50.4) years. Seven hundred eighty patients (53.2%) were never-smokers, 428 (29.2%) were ex-smokers, and 257 (17.5%) were current smokers. Main Outcome Measures: Smoking groups were compared for baseline clinical and magnetic resonance imaging characteristics as well as progression and sustained progression on the Expanded Disability Status Scale at 2 and 5 years and time to disease conversion to secondary progressive MS. In addition, the rate of on-study change in the brain parenchymal fraction and T2 hyperintense lesion volume were compared. Results: Current smokers had significantly worse disease at baseline than never-smokers in terms of Expanded Disability Status Scale score (adjusted P<.001), Multiple Sclerosis Severity Score (adjusted P<.001), and brain parenchymal fraction (adjusted P=.004). In addition, current smokers were significantly more likely to have primary progressive MS (adjusted odds ratio, 2.41; 95% confidence interval, 1.09-5.34). At longitudinal analyses, MS in smokers progressed from relapsing-remitting to secondary progressive disease faster than in neversmokers (hazard ratio for current smokers vs neversmokers, 2.50; 95% confidence interval, 1.42-4.41). In addition, in smokers, the T2-weighted lesion volume increased faster (P=.02), and brain parenchymal fraction decreased faster (P=.02). Conclusion: Our data suggest that cigarette smoke has an adverse influence on the progression of MS and accelerates conversion from a relapsing-remitting to a progressive course. [ABSTRACT FROM AUTHOR]

Objective: To determine whether concentration of serum urate, a purine metabolite and potent antioxidant that has been linked to a reduced risk of Parkinson disease (PD), predicts prognosis in PD. Design: Prospective study. Setting: The Parkinson Research Examination of CEP-1347 Trial (PRECEPT) study, which investigated the effects of a potential neuroprotectant on rates of PD progression, was conducted between April 2002 and August 2005 (average follow-up time 21.4 months). Participants: Eight hundred four subjects with early PD enrolled in the PRECEPT study. Main Outcome Measures: The primary study end point was progression to clinical disability sufficient to warrant dopaminergic therapy. Cox proportional hazards models were used to estimate the hazard ratio (HR) of reaching end point according to quintiles of baseline serum urate concentration, adjusting for sex, age, and other potential covariates. Change in striatal uptake of iodine I 123-labeled 2-beta-carbomethoxy-3-beta-(4-iodophenyl) tropane ([123I]β-CIT), amarker for the presynaptic dopamine transporter, was assessed with linear regression for a subset of 399 subjects. Results: The adjusted HR of reaching end point declined with increasing baseline concentrations of urate; subjects in the top quintile reached the end point at only half the rate of subjects in the bottom quintile (HR, 0.51; 95% confidence interval [CI], 0.37-0.72; P for trend<.001). This association was markedly stronger in men (HR, 0.39; 95% CI, 0.26-0.60; P for trend<.001) than in women (HR, 0.77; 95% CI, 0.39-1.50; P for trend=.33). The percentage of loss in striatal [123I]β-CIT uptake also improved with increasing serum urate concentrations (overall P for trend=.002; men, P=.001; women, P=.43). Conclusions: These findings identify serum urate as the first molecular factor directly linked to the progression of typical PD and suggest that targeting urate or its determinants could be an effective disease-modifying therapy inPD. [ABSTRACT FROM AUTHOR]

Context: Epidemiologic studies have reported that cigarette smoking is inversely associated with Parkinson disease (PD). However, questions remain regarding the effect of age at smoking onset, time since quitting, and race/ ethnicity that have not been addressed due to sample size constraints. This comprehensive assessment of the apparent reduced risk of PD associated with smoking may provide important leads for treatment and prevention. Objective: To determine whether race/ethnicity, sex, education, age at diagnosis, and type of tobacco modify the observed effects of smoking on PD. Design, Setting, and Participants: We conducted the first ever pooled analysis of PD combining individual level data from 8 US case-control and 3 cohort studies (Nurses' Health Study, Health Professionals Follow-Up Study, and Honolulu-Asia Aging Study) conducted between 1960 and 2004. Case-control studies provided data for 2328 PD cases and 4113 controls matched by age, sex, and ethnicity; cohort studies contributed 488 cases and 4880 controls selected from age- and sex-matched risk sets. Main Outcome Measure: Incident PD. Results: We confirmed inverse associations between PD and smoking and found these to be generally stronger in current compared with former smokers; the associations were stronger in cohort than in case-control studies. We observed inverse trends with pack-years smoked at every age at onset except the very elderly (75 years of age), and the reduction of risk lessened with years since quitting smoking. The risk reductions we observed for white and Asian patients were not seen in Hispanic and African American patients. We also found an inverse association both for smoking cigars and/or pipes and for chewing tobacco in male subjects. Conclusions: Our data support a dose-dependent reduction of PD risk associated with cigarette smoking and potentially with other types of tobacco use. Importantly, effects seemed not to be influenced by sex or education. Differences observed by race and age at diagnosis warrant further study. [ABSTRACT FROM AUTHOR]

The article presents a study on the relationship between high levels of vitamin D in the bloodstream and resistance to multiple sclerosis (MS. ) The U. S. Department of Defense Serum Repository provided serum samples of 257 U. S. military personnel known to have MS, and twice that number of control samples. The samples were analyzed for the presence of 25-hydroxyvitamin D, and levels of 100 nmol/L or higher correlated with a significantly reduced risk of MS. Levels that high were only found among samples of whites. Details of the methodology and results are presented.

Objective: To determine whether serum titers of anti-Epstein-Barr virus (EBV) antibodies are elevated in blood specimens collected up to 30 years prior to onset of multiple sclerosis (MS). Methods: Individuals with MS were identified among members of the Kaiser Permanente Northern California health plan who participated in the multiphasic examinations administered between 1965 and 1974. Stored serum samples were used to compare anti-EBV antibody titers in 42 individuals who developed MS with age matched and sex-matched controls. Results: The geometric mean titers of antibodies to the Epstein-Barr nuclear antigen (EBNA) complex and its component EBNA-1 were significantly higher in the MS cases when compared with matched controls. The relative risk of MS associated with a 4-fold increase in antibody titers was 2.1 (95% confidence interval, 1.1-3.8) for the EBNA complex and 1.8 (95% confidence interval, 1.1-2.9) for EBNA-1. Elevations of antibody titers to the EBNA complex and EBNA-1 among MS cases first occurred between 15 to 20 years before the onset of symptoms and persisted thereafter. Conclusion: The elevation of anti-EBV titers is probably an early event in the pathogenesis of MS and is unlikely to be the result of an a specific immune dysregulation. [ABSTRACT FROM AUTHOR]

Background Exogenous estrogens affect the onset and clinical course of experimental allergic encephalomyelitis. Oral contraceptives, a frequent source of exogenous estrogens in humans, could have a role in the development of multiple sclerosis (MS). Objective To examine whether recent oral contraceptive use and pregnancy history are associated with the risk of MS. Design and Setting A case-control study nested in the General Practice Research Database. This database contains prospective health information (drug prescriptions and clinical diagnoses) on more than 3 million Britons who are enrolled with selected general practitioners. Participants One hundred six female incident cases of MS, younger than 50 years, with at least 3 years of continuous recording in the General Practice Research Database before the date of first symptoms (index date), identified between January 1, 1993, and December 31, 2000, and 1001 controls matched on age, practice, and date of joining the practice. Main Outcome Measure Incidence of first symptoms of MS, confirmed through medical records. Results The incidence of MS was 40% lower (odds ratio, 0.6; 95% confidence interval, 0.4-1.0) in oral contraceptive users compared with nonusers during the previous 3 years. The risk of MS increased in the 6 months after pregnancy (odds ratio, 2.9, 95% confidence interval, 1.2-6.6), but it was not otherwise related to parity. Conclusions The hormonal changes that occur during oral contraceptive use and pregnancy may be associated with a short-term reduction in the risk of MS, and the postpartum period may be associated with a short-term increase in the risk of MS. [ABSTRACT FROM AUTHOR]

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce dopaminergic neuron degeneration in animal models of Parkinson disease (PD). However, no epidemiological data have been available on NSAID use and the risk of PD. Objective: To investigate prospectively whether the use of nonaspirin NSAIDs or aspirin is associated with decreased PD risk. Design, Settings, and Participants: Prospective cohorts of 44 057 men and 98 845 women free of PD, stroke, or cancer (Health Professionals Follow-up Study, 1986-2000, and Nurses' Health Study, 1980-1998). Main Outcome Measure: Newly diagnosed PD. Results: We documented 415 incident PD cases (236 men and 179 women). Participants who reported regular use of nonaspirin NSAIDs at the beginning of the study had a lower risk of PD than nonregular users during the follow-up; the pooled multivariate relative risk was 0.55 (95% confidence interval, 0.32-0.96, P = .04). Compared with nonusers, a nonsignificantly lower risk of PD was also observed among men and women who took 2 or more tablets of aspirin per day (relative risk, 0.56; 95% confidence interval, 0.26-1.21). Conclusion: These findings are consistent with the hypothesis that use of NSAIDs may delay or prevent the onset of PD. [ABSTRACT FROM AUTHOR]

The authors comment on an article about the inverse association between coffee consumption and depression. They emphasize the importance of isolating the effects of the caffeine from other facets of the coffee drinking experience. They also point out that the role of social support in preventing depressive episodes should not be minimized.