Lower Risk Of Parkinson's Disease Research Articles

Role of Glutathione in Parkinson's Disease Pathophysiology and Therapeutic Potential of Polyphenols.

Oxidative stress is recognized to have a central role in the initiation and progression of Parkinson's disease (PD). Within the brain, neurons are particularly sensitive to oxidation due in part to their weak intrinsic antioxidant defense. Theoretically, neurons mostly depend on neighboring astrocytes to provide antioxidant protection by supplying cysteine-containing products for glutathione (GSH) synthesis. Astrocytes and neurons possess several amino acid transport systems for GSH and its precursors. Indeed, GSH is the most abundant intrinsic antioxidant in the central nervous system. The GSH depletion and/or alterations in its metabolism in the brain contribute to the pathogenesis of PD. Noteworthy, polyphenols possess potent antioxidant activity and can augment the GSH redox system. Numerous in vitro and in vivo studies have indicated that polyphenols exhibit potent neuroprotective effects in PD. Epidemiological studies have found an association between the consumption of dietary polyphenols and a lower PD risk. In this review, we summarize current knowledge on the biosynthesis and metabolism of GSH in the brain, with an emphasis on their contribution and therapeutic potential in PD. In particular, we focus on polyphenols that can increase brain GSH levels against PD. Furthermore, some current challenges and future perspectives for polyphenol-based therapies are also discussed.

Glucagon-Like Peptide-1 Receptor Agonists and Risk of Parkinson's Disease in Patients with Type 2 Diabetes: A Population-Based Cohort Study.

Previous studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may have a disease-modifying effect in the development of Parkinson's disease (PD), but population studies yielded inconsistent results. The aim was to compare the risk of PD associated with GLP-1RAs compared to dipeptidyl peptidase 4 inhibitors (DPP4i) among older adults with type 2 diabetes (T2D). Using U.S. Medicare administrative data from 2016 to 2020, we conducted a population-based cohort study comparing the new use of GLP-1RA with the new use of DPP4i among adults aged ≥66 years with T2D. The primary endpoint was a new diagnosis of PD. A stabilized inverse probability of treatment weighting (sIPTW)-adjusted Cox proportional hazards regression model was employed to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for PD between GLP-1RA and DPP4i users. This study included 89,074 Medicare beneficiaries who initiated either GLP-1RA (n = 30,091) or DPP4i (n = 58,983). The crude incidence rate of PD was lower among GLP-1RA users than DPP4i users (2.85 vs. 3.92 patients per 1000 person-years). An sIPTW-adjusted Cox model showed that GLP-1RA users were associated with a 23% lower risk of PD than DPP4i users (HR, 0.77; 95% CI, 0.63-0.95). Our findings were largely consistent across different subgroup analyses such as sex, race, and molecular structure of GLP-1RA. Among Medicare beneficiaries with T2D, the new use of GLP-1RAs was significantly associated with a decreased risk of PD compared to the new use of DPP4i. © 2024 International Parkinson and Movement Disorder Society.

Air pollution, greenspace exposure and risk of Parkinson's disease: a prospective study of 441,462 participants.

The current understandings of the relationship between air pollution (AP), greenspace exposure and Parkinson's Disease (PD) remain inconclusive. We engaged 441,462 participants from the UK Biobank who were not diagnosed with PD. Utilizing Cox proportional hazard regression model, relationships between AP [nitrogen dioxide (NO2), and nitrogen oxides (NOX), particulate matter < 2.5μm in aerodynamic diameter(PM2.5), coarse particulate matter between 2.5μm and 10μm in aerodynamic diameter(PM2.5-10), particulate matter < 10μm in aerodynamic diameter(PM10)], greenspace exposure, and PD risk were determined independently. Our analyses comprised three models, adjusted for covariates, and affirmed through six sensitivity analyses to bolster the robustness of our findings. Moreover, mediation analysis was deployed to discern the mediating effect of AP between greenspaces and PD. During a median follow-up of 12.23years (5,574,293 person-years), there were 3,293 PD events. Each interquartile (IQR) increment in NO2 and PM10 concentrations were associated with 10% and 8% increase in PD onset risk, while the increases in NOX, PM2.5 and PM2.5-10 were not associated with PD risk. Additionally, greenspace may safeguard by reducing NO2 and PM10 levels, with the effect mediated by NO2 and PM10 in greenspace-PD relationship. Our findings indicate that an IQR increase in ambient NO2 and PM10 concentrations was associated with risk of PD development, while other pollutants (NOX, PM2.5 and PM2.5-10) were not associated with PD risk. Firstly, we find that augmented exposure to greenspace was associated with the lower PD risk by reducing NO2 and PM10 levels.

Contribution of Nutritional, Lifestyle, and Metabolic Risk Factors to Parkinson's Disease.

Modifiable risk factors for Parkinson's disease (PD) are poorly known. The aim is to evaluate independent associations of different nutritional components, physical activity, and sedentary behavior and metabolic factors with the risk of PD. In this population-based prospective cohort study using the data of the United Kingdom Biobank (from 2006-2010), 502,017 men and women who were free from PD (International Classification of Diseases 10th edition; "G20") at baseline were included. We implemented a Cox proportion hazard's model to evaluate the associations of different levels of physical activity, sitting time, sleep habits, diet quality, alcohol and coffee consumption, smoking, and body mass index with PD risk, adjusting for several confounding variables. During a median follow-up of 12.8 years, lifestyle factors including vigorous physical activity (hazard ration [HR] = 0.84; 95% confidence interval [CI], 0.75-0.94), low-to-moderate sitting time (HR = 0.89; 95% CI, 0.81-0.97), and high sleep quality (HR = 0.89; 95% CI, 0.80-0.99) were associated with a reduced risk of PD. Small amounts of coffee (HR = 0.88; 95% CI, 0.82-0.95), red meat (HR = 0.86; 95% CI, 0.76-0.97), and current smoking (HR = 0.65; 95% CI, 0.56-0.75) were also associated with a lower risk of PD, whereas alcohol intake (HR = 1.29; 95% CI, 1.06-1.56) with higher PD risk. Secondary analysis, including metabolic risk factors, confirmed these findings and highlighted the potential protective effect of plasma vitamin D and uric acid, but of low-density lipoprotein-cholesterol, triglycerides, and C-reactive protein as well. Vigorous physical activity, reduced sitting time, good sleep quality together with small coffee intake and vitamin D supplementation are potentially neuroprotective lifestyle interventions for the prevention of PD. © 2024 International Parkinson and Movement Disorder Society.

The role of peripheral inflammation-related biomarkers in distinguishing Parkinson's disease

BackgroundPeripheral inflammation plays a significant role in Parkinson's disease (PD). Conflicting studies on whether inflammatory indicators in blood could serve as biomarkers to distinguish PD. ObjectiveInclude a wider range of biomarkers and control confounding factors to comprehensively evaluate the value of peripheral inflammation-related indicators. MethodsA total of 80 PD patients were recruited and 80 one-to-one matched healthy controls (HCs). The levels of B-cell, T-cell, and natural killer (NK)-cell in blood were measured using flow cytometry. The levels of neurodegeneration-related proteins in serum were detected and clinical blood test results were collected. Multivariable logistic regression analysis was conducted to explore the role of significant variables in PD. Receiver operating characteristic curve analysis was performed to assess the potential value of these variables. ResultsCompared to HCs, PD patients showed lower levels of lymphocyte, B-cell, T-cell, high-density lipoprotein cholesterol (HDL-C) and lymphocyte-to-monocyte ratio, while the levels of neutrophil, NK-cell, β-amyloid40, neurofilament light chain, neutrophil-to-lymphocyte ratio, and neutrophil-to-HDL-C ratio (NHR) were increased. A higher B-cell count was associated with a lower risk of PD, while higher levels of NK-cell and NHR were associated with a higher risk of PD. B-cell, NK-cell and NHR have potential value in distinguishing PD from non-PD. B-cell and NHR levels were significantly correlated with PD dyskinesia scores. ConclusionsB-cell, NK-cell, and NHR may potentially contribute to distinguishing PD patients from HCs. There could be a correlation between the number of B-cell, the level of NHR, and the severity of PD dyskinesia.

Correlation between dietary factors and Parkinson's disease revealed by the analysis of Mendelian randomization.

The intricate interplay between dietary habits and the development of Parkinson's Disease (PD) has long been a subject of scientific inquiry. Mendelian Randomization (MR) emerges as a potent tool, harnessing genetic variants to infer causality in observational data. While evidence links diet to Parkinson's Disease (PD) etiology, a thorough MR exploration of dietary impacts on PD, particularly involving gut microbiota, is still emerging. This research leverages the IEU Open GWAS project's vast GWAS database to address the knowledge gap in understanding diet's influence on PD, employing a diverse range of dietary variables. Our holistic dataset includes various foods like processed fava beans, bap, red wine, to cheese, reflecting a commitment to untangling dietary complexities in PD etiology. Advancing from initial dietary-PD associations, we innovatively explore the gut microbiota, focusing on Parabacteroides goldsteinii, in relation to bap intake and PD, employing MR. Utilizing weighted median, MR-Egger, and inverse variance weighting methods, we ensure rigorous causality assessments, meticulously mitigating pleiotropy and heterogeneity biases to uphold finding validity. Our findings indicate red wine (OR: 1.031; 95% CI 1.001-1.062; p = 0.044) and dried fruit consumption (OR: 2.019; 95% CI 1.052-3.875; p = 0.035) correlate with increased PD risk, whereas broad beans (OR: 0.967; 95% CI 0.939-0.996; p = 0.024) and bap intake (OR: 0.922; 95% CI 0.860-0.989; p = 0.023) show protective effects against PD. Employing MR, specifically the IVW method, revealed a significant inverse association between bap intake and gut microbiota, marked by an 8.010-fold decrease in Parabacteroides goldsteinii per standard deviation increase in bap intake (95% CI 1.005-63.818, p = 0.049). Furthermore, a connection between PD and Parabacteroides goldsteinii was observed (OR: 0.810; 95% CI 0.768-0.999; p = 0.049), suggesting a potential microbiota-mediated pathway in PD etiology. Our study links dietary habits to PD risk, showing higher PD risk with red wine and dried fruit consumption, and a protective effect from broad beans and bap. Using MR, we found bap intake inversely correlates with Parabacteroides goldsteinii in the gut, suggesting bap influences microbiota. Further, higher Parabacteroides goldsteinii levels correlate with lower PD risk, highlighting a complex interplay of diet, gut microbiome, and neurological health. These insights shed light on potential dietary interventions for PD.

Association between major dietary patterns and Parkinson's disease risk: a case-control study.

There has been emerging attention to investigate the possible role of some dietary factors in the pathogenesis of Parkinson's disease (PD); however, evidence about the relationship between dietary components and the risk of PD is limited. The aim of this study was to determine the association between major dietary patterns and the risk of PD. This case-control study was performed on 105 patients with newly diagnosed PD and 215 healthy controls. Diagnosis of Parkinson's disease was made based on the UK Brain Bank criteria. Usual dietary intakes were collected by a validated semi-quantitative food frequency questionnaire. Dietary patterns were detected by principal component analysis. Four dietary patterns, including traditional, healthy, western, and light dietary patterns, were identified. After considering all potential confounders, individuals with the highest tertile of traditional dietary pattern scores had a lower risk of PD than those with the lowest tertile (OR: 0.002; 95% CI: 0.000-0.016). A similar inverse association between the healthy pattern (OR: 0.314; 95% CI: 0.131-0.750) and light pattern (OR: 0.282; 95% CI: 0.121-0.654) and risk of PD was revealed. In contrast, adherence to the western dietary pattern was associated with PD incidence (OR: 7.26; 95% CI: 2.76-19.09). The findings of this study suggest that adherence to western dietary pattern could increase the risk of PD by approximately seven times. However, the traditional, healthy, and light dietary patterns had an inverse relationship with PD risk.

Key Non-coding Variants in Three Neuroapoptosis and Neuroinflammation-Related LncRNAs Are Protectively Associated with Susceptibility to Parkinson's Disease and Some of Its Clinical Features.

Research findings show that genetic susceptibility to sporadic Parkinson's disease (PD), a common neurodegenerative disorder, is determined through gene variation of loci involved in its development and pathogenesis. A growing body of strong evidence has revealed that dysfunction of long non-coding RNAs (lncRNAs) plays key roles in the pathogenesis and progression of PD through impairing neuronal signaling pathways, but little is known about the relationship between their variants and PD susceptibility. In this research, we intended to study the relationship between functional SNPs rs12826786C>T, rs3200401C>T, and rs6931097G>A in the key lncRNAs stimulating neuroapoptosis and neuroinflammation in PD, including HOTAIR, MALAT1, and lincRNA-P21, respectively, with susceptibility to PD as well as its clinical symptoms.The population of this study consisted of 240 individuals, including 120 controls and 120 cases, and the sample taken from them was peripheral blood. Genotyping of the target SNPs was done using PCR-RFLP. We found that the healthy individuals carry more T allele of MALAT1-rs3200401C>T compared to the patients (P= 0.019). Furthermore, it was observed that in the dominant genetic model, subjects with genotypes carrying the T allele have a lower risk of PD (OR= 0.530; CI= 0.296-0.950; P= 0.033). Regarding the lincRNA-P21-rs6931097G>A, we observed a significant protective relationship between its GA (OR= 0.144; CI= 0.030-0.680; P= 0.014) and AA (OR= 0.195; CI= 00.047-0.799; P= 0.023) genotypes with the manifestation of tremor and bradykinesia symptoms, respectively. Furthermore, the findings indicated that the minor TT genotype of HOTAIR-rs12826786C>T was significantly associated with a reduced risk of bradykinesia symptoms (OR= 0.147; CI= 0.039-0.555; P= 0.005). Collectively, these findings suggest that MALAT1-rs3200401C>T may be an important lncRNA SNP against the development of PD, while the other two SNPs show protective effects on the clinical manifestations of PD in a way that lincRNA-P21-rs6931097G>A has a protective effect against the occurrence of tremor and bradykinesia symptoms in PD patients, and HOTAIR -rs12826786C>T indicates a protective effect against the display of bradykinesia feature. Therefore, they can have valuable potential as biomarkers for clinical evaluations of this disease.

Dietary approach to stop hypertension (DASH), but not Mediterranean and MIND, dietary pattern protects against Parkinson's disease.

The neuroprotective effects of dietary patterns have been reported in previous studies. This study aimed to examine the association between the dietary approach to stop hypertension (DASH), the Mediterranean diet (MeDi), and the Mediterranean-DASH intervention for neurodegenerative delay (MIND) with the severity and risk of Parkinson's disease (PD). In this comparative cross-sectional study, 120 patients with PD and 50 healthy participants participated. Adherence to DASH, MeDi, and MIND dietary patterns was determined according to the dietary intake data using a food frequency questionnaire (FFQ). The Severity of PD was determined by the Unified Parkinson's Disease Rating Scale (UPDRS). The mean score of the DASH was significantly lower in the PD group compared to the healthy group (p = .006), but the mean score of MeDi and MIND did not significantly differ between the two groups (p > .05). Also, the mean score of the DASH was significantly lower in men than in women in the healthy group (p = .018). High adherence to the DASH diet decreased the risk of PD by 15% (OR = 0.856, 95% CI: 0.751, 0.976, p = .020). Participants in quartiles 3 and 4 of the DASH dietary pattern had 86% (p = .003) and 87% (p = .007), respectively, lower risk of PD. MeDi and MIND diets were not significantly associated with the risk of PD. There was no significant association between dietary patterns and the severity of PD. The findings indicate that high adherence to the DASH dietary pattern may protect against PD.

Meta-analysis of Association between Newer Glucose-Lowering Drugs and Risk of Parkinson's Disease.

The association between newer classes of glucose-lowering drugs (GLDs) and the risk of Parkinson's disease (PD) remains unclear. The aim was to examine the effect of newer GLDs on the risk of PD through a meta-analysis of randomized outcome trials. The methods included randomized placebo-controlled outcome trials that reported PD events associated with three newer classes of GLDs (ie, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose co-transporter-2 inhibitors) in participants with or without type 2 diabetes. The pooled odds ratio (OR) and 95% confidence interval (CI) were estimated using Peto's method. The study included 24 trials involving 33 PD cases among 185,305 participants during a median follow-up of 2.2 years. Newer GLDs were significantly associated with a lower PD risk (OR: 0.50; 95% CI: 0.25-0.98) than placebo. Newer GLDs may possibly be associated with a decreased risk of PD; however, larger datasets are required to confirm or refute this notion.

Changes in smoking, alcohol consumption, and the risk of Parkinson's disease.

There have been no studies on the association between changes in smoking and alcohol consumption or combined changes in smoking and alcohol consumption frequencies and PD risk. To assess the influence of changes in smoking and alcohol consumption on the risk of Parkinson's disease (PD). National Health Insurance Service (NHIS) database between January 2009 to December 2011 was analyzed. A total of 3,931,741 patients were included. Study participants were followed up for the incidence of PD until December 2017. Compared to the sustained non-smokers, sustained light smokers (adjusted hazard ratio [aHR] 0.80, 95% confidence interval [CI] 0.75-0.85), sustained moderate smokers (aHR 0.54, 95% CI 0.47-0.61), and sustained heavy smokers (aHR 0.49, 95% CI 0.44-0.55) had a lower risk of PD. Compared to those who sustained non-drinking, sustained light drinkers (aHR 0.85 95% CI 0.89-0.91), sustained moderate drinkers (aHR 0.68, 95% CI 0.60-0.78), and sustained heavy drinkers (aHR 0.77, 95% CI 0.68-0.87) showed decreased risk of PD. Among non-drinkers, those who started drinking to a light level were at decreased risk of PD (aHR 0.84, 95% CI 0.77-0.91). Among non-smoking and non-drinking participants, those who initiated smoking only (aHR 0.78, 95% CI 0.70-0.86), drinking only (aHR 0.77, 95% CI 0.68-0.87), and both smoking and drinking (aHR 0.69, 95% CI 0.58-0.82) showed decreased risk of PD. Smoking is associated with decreased risk of PD with a dose-response relationship. Alcohol consumption at a light level may also be associated with decreased risk of PD. Further studies are warranted to find the possible mechanisms for the protective effects of smoking and drinking on PD, which may present insights into the etiology of PD.

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.

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. The aim was to examine the association of long-term intake of folate, vitamin B6, and vitamin B12 with the incidence of PD. 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. 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. 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.

Dietary Antioxidants and Risk of Parkinson’s Disease: A Systematic Review and Dose–Response Meta-analysis of Observational Studies

The aim of the current review was to explore the association between various dietary antioxidants and the risk of developing Parkinson's disease (PD). PubMed, Scopus, Web of Science, and Google Scholar were searched up to March 2021. Prospective, observational cohort studies, nested case-control, and case-control designs that investigated the association between antioxidants and PD risk were included. A random-effects model was used to pool the RRs. The certainty of the evidence was rated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluations) scoring system. In addition, a dose-response relation was examined between antioxidant intake and PD risk. Six prospective cohort studies and 2 nested case-control (total n=448,737 with 4654 cases), as well as 6 case-control (1948 controls, 1273 cases) studies were eligible. The pooled RR was significantly lower for the highest compared with the lowest intake categories of vitamin E (n=7; 0.84; 95% CI: 0.71, 0.99) and anthocyanins (n=2; 0.76; 95% CI: 0.61, 0.96) in cohort studies. Conversely, a significantly higher risk of PD was observed for higher lutein intake (n=3; 1.86; 95% CI: 1.20, 2.88) among case-control studies. Dose-response meta-analyses indicated a significant association between a 50-mg/d increase in vitamin C (n=6; RR: 0.94; 95% CI: 0.88, 0.99), a 5-mg/d increment in vitamin E (n=7; RR: 0.84; 95% CI: 0.70, 0.99), a 2-mg/d increment in β-carotene (n=6; RR: 0.94, 95% CI: 0.89, 0.99), and a 1-mg/d increment in zinc (n=1; OR: 0.65; 95% CI: 0.49, 0.86) and a reduced risk of PD. Overall, higher intake of antioxidant-rich foods may be associated with a lower risk of PD. Future well-designed prospective studies are needed to validate the present findings. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (https://www.crd.york.ac.uk/PROSPERO, CRD42021242511).

Disease-Modifying Antirheumatic Drugs and Risk of Parkinson Disease: Nested Case-Control Study of People With Rheumatoid Arthritis.

Background and ObjectivesEpidemiologic studies have suggested a link between rheumatoid arthritis and Parkinson disease (PD). Disease-modifying antirheumatic drugs (DMARDs) might explain this association. The aim of this work was to evaluate the association between DMARDs and risk of PD in persons with rheumatoid arthritis.MethodsThis nested nationwide case-control study was conducted within the Finnish Parkinson's Disease (FINPARK) cohort, which includes 22,189 Finnish persons with clinically verified PD diagnosed in 1996 to 2015. The cases had recorded diagnosis of PD in the Special Reimbursement Register and had no exclusion diagnoses with symptoms that may be confused with PD within 2 years of PD diagnosis. This study included cases with PD diagnosed during 1999 to 2015 and rheumatoid arthritis diagnosed >3 years before PD. Rheumatoid arthritis was identified from the Finnish Care Register for Health Care and Special Reimbursement Register. Cases were matched with up to 7 controls by age, sex, duration of rheumatoid arthritis, and region. DMARDs were categorized into 5 classes, and data on purchased prescriptions were identified from the Prescription Register since 1995. Associations were studied with conditional logistic regression adjusted for confounders.ResultsAltogether, 315 cases with PD and 1,571 matched controls were included. The majority (>60%) were women, and the median duration of rheumatoid arthritis on matching date was 11.6 years for controls and 12.6 years for cases. Use of DMARDs was not associated with risk of PD with a 3-year lag period applied between exposure and outcome except chloroquine/hydroxychloroquine, which associated with decreased risk (adjusted odds ratio [OR] 0.74, 95% confidence interval [CI] 0.56–0.97). Other DMARDs, including sulfasalazine, methotrexate, gold preparations, and immunosuppressants, were not associated with PD.DiscussionOur results suggest that the lower risk of PD in people with rheumatoid arthritis is not explained by DMARD use because these drugs in general did not modify the risk of PD among persons with rheumatoid arthritis. Association between chloroquine/hydroxychloroquine and lower risk of PD and the possible underlying mechanisms should be further investigated.Classification of EvidenceThis study provides Class II evidence that in individuals with rheumatoid arthritis using DMARDs, only chloroquine/hydroxychloroquine was associated with a potentially decreased risk of developing PD (adjusted OR 0.74, 95% CI 0.56–0.97).

Editors' Note: Dietary Antioxidants and the Risk of Parkinson Disease: The Swedish National March Cohort

In “Dietary Antioxidants and the Risk of Parkinson Disease: The Swedish National March Cohort,” Hantikainen et al. surveyed dietary intake through a food frequency questionnaire from 1997 to 2016 and found that higher dietary vitamin E and vitamin C were associated with a lower risk of Parkinson disease. They found no relationship between beta-carotene intake or nonenzymatic antioxidant capacity and Parkinson disease. Kawada notes that a previous study found beta-carotene and vitamin E intake was inversely associated with a risk of Parkinson disease, but there was no significant relationship between intake of vitamin C and nonenzymatic antioxidant capacity and Parkinson disease. They suggest that sex differences may be relevant to these findings. Hantikainen et al. acknowledge that there are discrepancies across studies, but they did not find any sex differences. Both authors agree more research is needed to evaluate the relationship between antioxidants and Parkinson disease and whether there are sex differences that might play a role. In “Dietary Antioxidants and the Risk of Parkinson Disease: The Swedish National March Cohort,” Hantikainen et al. surveyed dietary intake through a food frequency questionnaire from 1997 to 2016 and found that higher dietary vitamin E and vitamin C were associated with a lower risk of Parkinson disease. They found no relationship between beta-carotene intake or nonenzymatic antioxidant capacity and Parkinson disease. Kawada notes that a previous study found beta-carotene and vitamin E intake was inversely associated with a risk of Parkinson disease, but there was no significant relationship between intake of vitamin C and nonenzymatic antioxidant capacity and Parkinson disease. They suggest that sex differences may be relevant to these findings. Hantikainen et al. acknowledge that there are discrepancies across studies, but they did not find any sex differences. Both authors agree more research is needed to evaluate the relationship between antioxidants and Parkinson disease and whether there are sex differences that might play a role.

Lower Parkinson's Disease Risk Linked to Prostate Drug Terazosin

Clinical OMICsVol. 8, No. 2 NewsLower Parkinson's Disease Risk Linked to Prostate Drug TerazosinPublished Online:9 Apr 2021https://doi.org/10.1089/clinomi.08.02.08AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Lower Parkinson's Disease Risk Linked to Prostate Drug Terazosin." Clinical OMICs, 8(2), p. 8FiguresReferencesRelatedDetails Volume 8Issue 2Mar 2021 InformationCopyright © GEN PublishingTo cite this article:Lower Parkinson's Disease Risk Linked to Prostate Drug Terazosin.Clinical OMICs.Mar 2021.8-8.http://doi.org/10.1089/clinomi.08.02.08Published in Volume: 8 Issue 2: April 9, 2021PDF download

Non-genetic risk and protective factors and biomarkers for neurological disorders: a meta-umbrella systematic review of umbrella reviews

BackgroundThe etiologies of chronic neurological diseases, which heavily contribute to global disease burden, remain far from elucidated. Despite available umbrella reviews on single contributing factors or diseases, no study has systematically captured non-purely genetic risk and/or protective factors for chronic neurological diseases.MethodsWe performed a systematic analysis of umbrella reviews (meta-umbrella) published until September 20th, 2018, using broad search terms in MEDLINE, SCOPUS, Web of Science, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, ProQuest Dissertations & Theses, JBI Database of Systematic Reviews and Implementation Reports, DARE, and PROSPERO. The PRISMA guidelines were followed for this study. Reference lists of the identified umbrella reviews were also screened, and the methodological details were assessed using the AMSTAR tool. For each non-purely genetic factor association, random effects summary effect size, 95% confidence and prediction intervals, and significance and heterogeneity levels facilitated the assessment of the credibility of the epidemiological evidence identified.ResultsWe identified 2797 potentially relevant reviews, and 14 umbrella reviews (203 unique meta-analyses) were eligible. The median number of primary studies per meta-analysis was 7 (interquartile range (IQR) 7) and that of participants was 8873 (IQR 36,394). The search yielded 115 distinctly named non-genetic risk and protective factors with a significant association, with various strengths of evidence. Mediterranean diet was associated with lower risk of dementia, Alzheimer disease (AD), cognitive impairment, stroke, and neurodegenerative diseases in general. In Parkinson disease (PD) and AD/dementia, coffee consumption, and physical activity were protective factors. Low serum uric acid levels were associated with increased risk of PD. Smoking was associated with elevated risk of multiple sclerosis and dementia but lower risk of PD, while hypertension was associated with lower risk of PD but higher risk of dementia. Chronic occupational exposure to lead was associated with higher risk of amyotrophic lateral sclerosis. Late-life depression was associated with higher risk of AD and any form of dementia.ConclusionsWe identified several non-genetic risk and protective factors for various neurological diseases relevant to preventive clinical neurology, health policy, and lifestyle counseling. Our findings could offer new perspectives in secondary research (meta-research).

Gastrectomy, vitamin B12 supplementation and the risk of Parkinson's disease: A nationwide cohort study

IntroductionPrevious evidence has suggested roles for α-synuclein propagation and vitamin B12 (VitB12) deficiency in the pathogenesis of Parkinson's disease (PD). We investigated whether gastric cancer (GC) patients who underwent gastrectomy had a lower risk of PD and whether VitB12 supplementation modified the risk. MethodsGC patients aged ≥50 years who underwent curative gastrectomy between 2007 and 2012 (n = 72,216) and matched comparison groups (n = 211,389) were identified from the Korean National Health Insurance database. The risks of PD were analyzed by Cox regression. ResultsCompared to their matched comparison groups, GC patients who underwent gastrectomy showed a decreased risk of PD (adjusted HR [aHR] 0.86; 95% confidence interval [CI] 0.75–0.98), but the significance disappeared after further adjustment with smoking and body mass index (BMI). To elaborate, subtotal gastrectomy (STG) was associated with decreased risk of PD (aHR 0.85; 95% CI 0.74–0.99) while total gastrectomy (TG) was not (aHR 0.89; 95% CI 0.66–1.19), although the risk reduction was not significant when further adjusted for smoking and BMI. Among the patients who underwent TG, their risk of PD was markedly lower when they had VitB12 supplementation after surgery (aHR 0.36; 95% CI 0.17–0.76), while the risk was higher when they did not have any (aHR 1.55; 95% CI 1.03–2.32). ConclusionsGC patients who underwent gastrectomy and received uninterrupted VitB12 supplementation had a decreased incidence of PD. This study provides indirect epidemiological evidence for the potential roles of gastrectomy and VitB12 in the pathogenesis of PD.

Dietary Antioxidants and the Risk of Parkinson Disease: The Swedish National March Cohort.

To determine whether high baseline dietary antioxidants and total nonenzymatic antioxidant capacity (NEAC) is associated with a lower risk of Parkinson disease (PD) in men and women, we prospectively studied 43,865 men and women from a large Swedish cohort. In the Swedish National March Cohort, 43,865 men and women aged 18-94 years were followed through record linkages to National Health Registries from 1997 until 2016. Baseline dietary vitamin E, vitamin C, and beta-carotene intake, as well as NEAC, were assessed by a validated food frequency questionnaire collected at baseline. All exposure variables were adjusted for energy intake and categorized into tertiles. Multivariable Cox proportional hazard regression models were fitted to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for PD. After a mean follow-up time of 17.6 years, we detected 465 incidence cases of PD. In the multivariable adjusted model, dietary vitamin E (HR 0.68, 95% CI 0.52-0.90; p for trend 0.005) and vitamin C (HR 0.68, 95% CI 0.52-0.89; p for trend 0.004) were inversely associated with the risk of PD when comparing participants in the highest vs the lowest tertiles of exposure. No association was found with estimated intake of dietary beta-carotene or NEAC. Our findings suggest that dietary vitamin E and C intake might be inversely associated with the risk of PD. No association was found with dietary beta-carotene or NEAC. This study provides Class III evidence that dietary vitamin E and C intake are inversely associated with the risk of PD.

Diet Quality and Risk of Parkinson's Disease: A Prospective Study and Meta-Analysis.

Several dietary components have been shown to be neuroprotective against risk of neurodegeneration. However, limited observational studies have examined the role of overall diet quality on risk of Parkinson's disease. We examined the associations between diet quality and risk of Parkinson's disease in a prospective cohort study and meta-analysis. Included in the cohort study were 3,653 participants (1,519 men and 2,134 women; mean age: 81.5 years) in the Geisinger Rural Aging Study longitudinal cohort in Pennsylvania. Diet quality was assessed using a validated dietary screening tool containing 25 food- and behavior-specific questions in 2009. Potential Parkinson's cases were identified using electronic health records based on ICD9 (332.*), ICD10 (G20), and Parkinson-related treatments. Hazard ratios (HRs) and 95% confidence intervals (CIs) across diet quality tertiles were calculated using Cox proportional hazards models after adjusting for potential confounders. We further performed a meta-analysis by pooling our study with four published papers on this topic. Random-effects model was utilized to calculate the pooled risk ratios and 95% CIs. During a mean of 6.94 years of follow-up, 47 incident Parkinson's cases were documented. Having high diet quality at baseline was associated with lower Parkinson's disease risk (adjusted HR for the highest vs the lowest diet quality tertile = 0.39; 95% CI: 0.17, 0.89; p-trend = 0.02). The meta-analysis including 140,617 individuals also showed that adherence to high diet quality or a healthy dietary pattern was associated with lower risk of Parkinson's disease (pooled risk ratio = 0.64; 95% CI: 0.49, 0.83). Having high diet quality or a healthy dietary pattern was associated with lower future risk of Parkinson's disease.