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.

Multigenerational Association Between Smoking and Autism Spectrum Disorder: Findings from a Nation-Wide Prospective Cohort Study.

Animal studies have shown that exposure to cigarette smoke during pregnancy can induce neurobehavioral anomalies in multiple subsequent generations. However, little work has examined such effects in humans. We examined the risk of grandchild autism spectrum disorder (ASD) in association with grandmother smoking during pregnancy, using data from 53,562 mothers and grandmothers, and 120,267 grandchildren in the Nurses' Health Study II using nurse reporting in 1999 of her mother's smoking. Grandchildren's ASD diagnoses were reported by the mothers in 2005 and 2009. Among grandmothers, 13,383 (25.0%) smoked during pregnancy, and 509 (0.4%) grandchildren were diagnosed with ASD. The adjusted odds ratio (aOR) of ASD for grandmother smoking during pregnancy was 1.52 (95% confidence limit [CI]: 1.06, 2.20). Results were similar with direct grandmother reporting in 2001 of her smoking during pregnancy from the Nurses' Mothers Cohort Study subgroup (n=22,167 grandmothers, 49,917 grandchildren) and stronger among grandmothers who smoked ≥15 cigarettes per day during pregnancy (aOR=1.93; 95% CI: 1.10, 3.40; n=1,895 grandmothers, 4,212 grandchildren). Results were similar when adjusted for mother's smoking during pregnancy. There was no association with grandfather's smoking as reported by the grandmother. Our results suggest potential persistent impact of gestational exposure to environmental insults across three generations.

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.

Plasma metabolites of a healthy lifestyle in relation to mortality and longevity: Four prospective US cohort studies.

BACKGROUND: A healthy lifestyle is associated with a lower premature mortality risk and with longer life expectancy. However, the metabolic pathways of a healthy lifestyle and how they relate to mortality and longevity are unclear. We aimed to identify and replicate a healthy lifestyle metabolomic signature and examine how it is related to total and cause-specific mortality risk and longevity. METHODS: In four large cohorts with 13,056 individuals and 28-year follow-up, we assessed five healthy lifestyle factors, used liquid chromatography mass spectrometry to profile plasma metabolites, and ascertained deaths with death certificates. The unique healthy lifestyle metabolomic signature was identified using an elastic regression. Multivariable Cox regressions were used to assess associations of the signature with mortality and longevity. FINDINGS: The identified healthy lifestyle metabolomic signature was reflective of lipid metabolism pathways. Shorter and more saturated triacylglycerol and diacylglycerol metabolite sets were inversely associated with the healthy lifestyle score, whereas cholesteryl ester and phosphatidylcholine plasmalogen sets were positively associated. Participants with a higher healthy lifestyle metabolomic signature had a 17% lower risk of all-cause mortality, 19% for cardiovascular disease mortality, and 17% for cancer mortality and were 25% more likely to reach longevity. The healthy lifestyle metabolomic signature explained 38% of the association between the self-reported healthy lifestyle score and total mortality risk and 49% of the association with longevity. CONCLUSIONS: This study identifies a metabolomic signature that measures adherence to a healthy lifestyle and shows prediction of total and cause-specific mortality and longevity. FUNDING: This work was funded by the NIH, CIHR, AHA, Novo Nordisk Foundation, and SciLifeLab.

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 during pregnancy and risk of multiple sclerosis in offspring and mother: A Danish nationwide register-based cohort study.

BACKGROUND: The association between intra-uterine exposure to maternal smoking and risk of multiple sclerosis (MS) has been little studied and with conflicting results. OBJECTIVE: To examine the risk of MS in offspring exposed intra-uterine to maternal smoking. In addition, to re-examine prior observations of an elevated risk of MS among smokers, assuming that self-reported smoking during pregnancy reflects the woman's general smoking habits. METHODS: The study cohort included all Danish women, pregnant in the period 1991-2018, (n = 789,299) and singletons from these pregnancies (n = 879,135). Nationwide information on maternal smoking during pregnancy and MS cases in the study cohort were obtained from the Medical Birth Register and the National Patient Register. Cox regression analysis was used to estimate hazard ratios (HRs) for the association between smoking and MS risk. RESULTS: Women who smoked during pregnancy had a 42% increased risk of developing MS compared with non-smoking women (HR = 1.42 (1.32-1.52), n = 1,296). The risk of MS among singletons of women who smoked during pregnancy was 38% higher than that among singletons born to non-smoking women (HR = 1.38 (1.08-1.76), n = 110). CONCLUSION: Our observations add further to the evidence implicating smoking in the development of MS and suggest that intra-uterine exposure to tobacco smoke may increase MS risk.

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.

Probable Parasomnias and Mortality: A Prospective Study in US Men.

OBJECTIVE: To examine the association between parasomnias, including rapid eye movement sleep behavior disorder (RBD) and sleep walking (SW), and mortality risk in a large-scale population-based cohort. METHODS: This prospective cohort study was based on 25,695 participants from the Health Professionals Follow-up Study, a population-based cohort of male health professionals in the United States. Probable SW (pSW) and probable RBD (pRBD) were measured by questions adapted from the Mayo Sleep Questionnaire in 2012. All-cause mortality and cause-specific mortality were ascertained through the national registry, reports by the families, and the postal system from January 1, 2012, through June 30, 2018. RESULTS: Of the studied population, 223 reported pSW and 2720 reported pRBD. During 6 years of follow-up (2012 to 2018), 4743 mortality cases were documented. The co-occurrence of both probable parasomnias was associated with higher all-cause mortality risk (Ptrend=.008), and the adjusted hazard ratio (HR) of mortality was 1.65 (95% CI, 1.20 to 2.28) compared with participants without either probable parasomnia after adjustment for major lifestyle, sleep, and metabolic risk factors, and chronic diseases. Significant associations were found for mortality attributed to neurodegenerative diseases (adjusted HR for both parasomnias vs none, 4.57; 95% CI, 2.62 to 7.97) and accidents (adjusted HR for both parasomnias vs none, 7.36; 95% CI, 2.95 to 18.4). Having pSW alone was associated with all-cause mortality, and pSW and pRBD were individually associated with mortality attributed to neurodegenerative diseases and accidents too (P<.05 for all). CONCLUSION: Probable parasomnia was associated with a higher risk of all-cause mortality and mortality attributed to neurodegenerative diseases and accidents.

Association Between Bowel Movement Pattern and Cognitive Function: Prospective Cohort Study and a Metagenomic Analysis of the Gut Microbiome.

BACKGROUND AND OBJECTIVES: Little is known regarding the association between intestinal motility patterns and cognitive function in individuals who are baseline cognitively healthy. The gut microbiome may contribute to the association. We examined the association between bowel movement (BM) pattern and cognitive function and explored the role of the gut microbiome in explaining this association. METHODS: In this prospective study, we leveraged 3 cohort studies, Nurses' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (HPFS). Participants reported BM frequency and subjective cognitive function. In a subset of NHSII participants, we assessed cognitive function using an objective neuropsychological battery. We profiled the gut microbiome in a subset of participants using whole-genome shotgun metagenomics. General linear models, Poisson regression, and logistic regression were used to quantify the association of BM frequency with different cognitive measurements. RESULTS: We followed 112,753 men and women (women: 87.6%) with a mean age of 67.2 years at baseline (NHS: 76 years, NHSII: 59 years, HPFS: 75 years) for a median follow-up of 4 years (NHSII and HPFS: 4 years, NHS: 2 years). Compared with those with BM once daily, participants with BM frequency every 3+ days had significantly worse objective cognitive function, equivalent to 3.0 (95% confidence interval [CI],1.2-4.7) years of chronological cognitive aging. We observed similar J-shape dose-response relationships of BM frequency with the odds of subjective cognitive decline and the likelihood of having more subsequent subjective cognitive complaints (both p nonlinearity < 0.001). BM frequencies of every 3+ days and ≥twice/day, compared with once daily, were associated with the odds ratios of subjective cognitive decline of 1.73 (95% CI 1.60-1.86) and 1.37 (95% CI 1.33-1.44), respectively. BM frequency and subjective cognitive decline were significantly associated with the overall gut microbiome configuration (both p < 0.005) and specific microbial species in the 515 participants with microbiome data. Butyrate-producing microbial species were depleted in those with less frequent BM and worse cognition, whereas a higher abundance of proinflammatory species was associated with BM frequency of ≥twice/day and worse cognition. DISCUSSION: Lower BM frequency was associated with worse cognitive function. The gut microbial dysbiosis may be a mechanistic link underlying the association.

The STEPWISE study: study protocol for a smartphone-based exercise solution for people with Parkinson's Disease (randomized controlled trial).

BACKGROUND: Exercise has various health benefits for people with Parkinson's disease (PD). However, implementing exercise into daily life and long-term adherence remain challenging. To increase a sustainable engagement with physical activity of people with PD, interventions that are motivating, accessible, and scalable are needed. We primarily aim to investigate whether a smartphone app (STEPWISE app) can increase physical activity (i.e., step count) in people with PD over one year. Our second aim is to investigate the potential effects of the intervention on physical fitness, and motor- and non-motor function. Our third aim is to explore whether there is a dose-response relationship between volume of physical activity and our secondary endpoints. METHODS: STEPWISE is a double-blind, randomized controlled trial. We aim to include 452 Dutch people with PD who can walk independently (Hoehn & Yahr stages 1-3) and who do not take more than 7,000 steps per day prior to inclusion. Physical activity levels are measured as step counts on the participant's own smartphone and scaled as percentage of each participant's baseline. Participants are randomly assigned to an active control group with an increase of 5-20% (active controls) or any of the three intervention arms with increases of 25-100% (intermediate dose), 50-200% (large dose), or 100-400% (very large dose). The primary endpoint is change in step count as measured by the STEPWISE smartphone app from baseline to 52 weeks. For our primary aim, we will evaluate the between-group difference in average daily step count change from baseline to 52 weeks. For our second aim, measures of physical fitness, and motor- and non-motor function are included. For our third aim, we will associate 52-week changes in step count with 52-week changes in secondary outcomes. DISCUSSION: This trial evaluates the potential of a smartphone-based intervention to increase activity levels in people with PD. We envision that motivational apps will increase adherence to physical activity recommendations and could permit conduct of remote clinical trials of exercise for people with PD or those at risk of PD. TRIAL REGISTRATION: ClinicalTrials.gov; NCT04848077; 19/04/2021. CLINICALTRIALS: gov/ct2/show/NCT04848077.

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.

Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness in older adults. Investigating shared genetic components between metabolites and AMD can enhance our understanding of its pathogenesis. We conduct metabolite genome-wide association studies (mGWASs) using multi-ethnic genetic and metabolomic data from up to 28,000 participants. With bidirectional Mendelian randomization analysis involving 16,144 advanced AMD cases and 17,832 controls, we identify 108 putatively causal relationships between plasma metabolites and advanced AMD. These metabolites are enriched in glycerophospholipid metabolism, lysophospholipid, triradylcglycerol, and long chain polyunsaturated fatty acid pathways. Bayesian genetic colocalization analysis and a customized metabolome-wide association approach prioritize putative causal AMD-associated metabolites. We find limited evidence linking urine metabolites to AMD risk. Our study emphasizes the contribution of plasma metabolites, particularly lipid-related pathways and genes, to AMD risk and uncovers numerous putative causal associations between metabolites and AMD risk.

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.

Association of the Mediterranean Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) Diet With the Risk of Dementia.

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.

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.