Niacin metabolism and Parkinson’s disease

Epidemiological surveys suggest an important role for niacin in the causes of Parkinson’s disease, in that niacin deficiency, the nutritional condition that causes pellagra, appears to protect against Parkinson’s disease. Absorbed niacin is used in the synthesis of nicotinamide adenine dinucleotide (NAD) in the body, and in the metabolic process NAD releases nicotinamide by poly(ADP-ribosyl)ation, the activation of which has been reported to mediate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s disease. Recently nicotinamide N-methyltransferase (EC2.1.1.1) activity has been discovered in the human brain, and the released nicotinamide may be methylated to 1-methylnicotinamide (MNA), via this enzyme, in the brain. A deficiency in mitochondrial NADH: ubiquinone oxidoreductase (complex 1) activity is believed to be a critical factor in the development of Parkinson’s disease. MNA has been found to destroy several subunits of cerebral complex 1, leading to the suggestion that MNA is concerned in the pathogenesis of Parkinson’s disease. Based on these findings, it is hypothesized that niacin is a causal substance in the development of Parkinson’s disease through the following processes: NAD produced from niacin releases nicotinamide via poly(ADP-ribosyl)ation, activated by the hydroxyl radical. Released excess nicotinamide is methylated to MNA in the cytoplasm, and superoxides formed by MNA via complex I destroy complex 1 subunits directly, or indirectly via mitochondrial DNA damage. Hereditary or environmental factors may cause acceleration of this cycle, resulting in neuronal death.     

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

The respective contribution of occupational and behavioural factors to social disparities in all-cause mortality has been studied very seldom. The objective of this study was to evaluate the role of occupational and behavioural factors in explaining social inequalities in premature and total mortality in the French working population. The study population consisted of a sample of 2,189 and 1,929 French working men and women, who responded to a self-administered questionnaire in mid-1996, and were followed up until the end of 2008. Mortality was derived from register-based information and linked to the baseline data. Socioeconomic status was measured using occupation. Occupational factors included biomechanical and physical exposures, temporary contract, psychological demands, and social support, and behavioural factors, smoking, alcohol abuse, and body mass index. Significant social differences were observed for premature and total mortality. Occupational factors reduced the hazard ratios of mortality for manual workers compared to managers/professionals by 72 and 41%, from 1.88 (95% CI: 1.17–3.01) to 1.25 (95% CI: 0.74–2.12) for premature mortality, and from 1.71 (95% CI: 1.18–2.47) to 1.42 (95% CI: 0.95–2.13) for total mortality. The biggest contributions were found for biomechanical and physical exposures, and job insecurity. The role of behavioural factors was very low. Occupational factors played a substantial role in explaining social disparities in mortality, especially for premature mortality and men. Improving working conditions amongst the lowest social groups may help to reduce social inequalities in mortality.     

Vitamin D levels in Alzheimer’s and Parkinson’s diseases: A meta-analysis

ObjectiveRecent accumulating evidence shows that vitamin D deficiency is prevalent in individuals with AD and PD. The purpose of the present study is to perform a meta-analysis on the 25-hydroxyvitamin D (25(OH)D) status in this population of patients.MethodsWe searched all articles in English published up to March 2012 concerning the 25(OH)D level in AD and PD patients. For AD, six studies covering 319 patients and 573 controls were included in the meta-analysis. For PD, five studies discussing 434 patients and 3451 controls were included.ResultsIt was found that AD patients had lower levels of 25(OH)D than healthy controls (summary standardized mean difference [SMD], -1.39; 95% confidence interval [CI], -2.79 to 0.01). Similar results were found for PD patients versus healthy controls (summary SMD, -1.33; 95% CI, -2.44 to -0.21).ConclusionThe results indicate that despite the similar mean age between patients and healthy controls in each identified study, both AD and PD patients have lower levels of 25(OH)D than controls.     

Multiple Antioxidants in the Prevention and Treatment of Parkinson’s Disease

Parkinson’s disease (PD) is one of the major progressive neurological disorders for which no preventative or long-term effective treatment strategies are available. Epidemiologic studies have failed to identify specific environmental, dietary or lifestyle risk factors for PD except for toxic exposure to manganese, meperidine (Demerol®, the “designer drug” version of which often contains a toxic byproduct of the synthesis, 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine [MPTP]), and some herbicides and pesticides. The search for genetic risk factors such as mutation, overexpression or underexpression of nuclear genes in DA neurons in idiopathic PD has not been successful as yet. Polymorphism in certain genes appears to be a risk factor, but there is no direct evidence for the causal relationship between polymorphism and increased risk of PD. In familial PD, mutation in the α-synuclein gene is associated with the disease, but a direct role of this gene in degeneration of DA neurons remains to be established. Although mutations in the Parkin gene has been associated with autosomal recessive juvenile Parkinson’s disease, the role of this gene mutation in causing degeneration of DA neurons has not been defined. We have reported that in hereditary PD, a mutation in the α-synuclein gene may increase the sensitivity of DA neurons to neurotoxins. We hypothesize that, in idiopathic PD, epigenetic (mitochondria, membranes, protein modifications) rather than genetic events are primary targets which, when impaired, initiate degeneration in DA neurons, eventually leading to cell death. Although the nature of neurotoxins that cause degeneration in DA neurons in PD is not well understood, oxidative stress is one of the intermediary risk factors that could initiate and/or promote degeneration of DA neurons. Therefore, supplementation with antioxidants may prevent or reduce the rate of progression of this disease. Supplementation with multiple antioxidants at appropriate doses is essential because various types of free radicals are produced, antioxidants vary in their ability to quench different free radicals and cellular environments vary with respect to their lipid and aqueous phases. L-dihydroxyphenylalanine (L-dopa) is one of the agents used in the treatment of PD. Since L-dopa is known to produce free radicals during its normal metabolism, the combination of L-dopa with high levels of multiple antioxidants may improve the efficacy of L-dopa therapy.     

Paraquat exposure and Parkinson’s disease: A systematic review and meta-analysis

Abstract

To reconcile and unify available results regarding paraquat exposure and Parkinson’s disease (PD), we conducted a systematic review and meta-analysis to provide a quantitative estimate of the risk of PD associated with paraquat exposure. Six scientific databases including PubMed, Cochrane libraries, EMBASE, Scopus, ISI Web of Knowledge, and TOXLINE were systematically searched. The overall odds ratios (ORs) with corresponding 95% CIs were calculated using a random-effects model. Of 7,309 articles identified, 13 case control studies with 3,231 patients and 4,901 controls were included into our analysis. Whereas, one prospective cohort studies was included into our systematic review. A subsequent meta-analysis showed an association between PD and paraquat exposure (odds ratio?=?1.64 (95% CI: 1.27–2.13; I²?=?24.8%). There is a statistically significant association between paraquat exposure and PD. Thus, future studies regarding paraquat and Parkinson’s disease are warranted.     

Manganese and Parkinson’s Disease: A Critical Review and New Findings

Background

Excess accumulation of manganese (Mn) in the brain results in a neurological syndrome with cognitive, psychiatric, and movement abnormalities. The highest concentrations of Mn in the brain are achieved in the basal ganglia, which may precipitate a form of parkinsonism with some clinical features that are similar and some that are different to those in Parkinson’s disease (PD). Recently, scientists have debated the possibility that Mn may have an etiological role in PD or that it may accelerate the expression of PD.

Objective

The goal of this review was to examine whether chronic Mn exposure produces dopamine neuron degeneration and PD or whether it has a distinct neuropathology and clinical presentation.

Data source

I reviewed available clinical, neuroimaging, and neuropathological studies in humans and nonhuman primates exposed to Mn or other human conditions that result in elevated brain Mn concentrations.

Data extraction

Human and nonhuman primate literature was examined to compare clinical, neuroimaging, and neuropathological changes associated with Mn-induced parkinsonism.

Data synthesis

Clinical, neuroimaging, and neuropathological evidence was used to examine whether Mn-induced parkinsonism involves degeneration of the nigrostriatal dopaminergic system as is the case in PD.

Conclusions

The overwhelming evidence shows that Mn-induced parkinsonism does not involve degeneration of midbrain dopamine neurons and that l-dopa is not an effective therapy. New evidence is presented on a putative mechanism by which Mn may produce movement abnormalities. Confirmation of this hypothesis in humans is essential to make rational decisions about treatment, devise effective therapeutic strategies, and set regulatory guidelines.     

The NYU Children’s Health and Environment Study

European Journal of Epidemiology - The aims of the NYU Children’s Health and Environment Study (CHES) are to evaluate influences of prenatal non-persistent chemical exposures on fetal and...     

Agricultural activities and the incidence of Parkinson’s disease in the general French population

Most studies on pesticides and Parkinson’s disease (PD) focused on occupational exposure in farmers. Whether non-occupational exposure is associated with PD has been little explored. We investigated the association between agricultural characteristics and PD incidence in a French nationwide ecologic study. We hypothesized that persons living in regions with agricultural activities involving more intensive pesticide use would be at higher risk. We identified incident PD cases from French National Health Insurance databases (2010–2012). The proportion of land dedicated to 18 types of agricultural activities was defined at the canton of residence level. We examined the association between agricultural activities and PD age/sex-standardized incidence ratios using multivariable multilevel Poisson regression adjusted for smoking, deprivation index, density of neurologists, and rurality (proportion of agricultural land); we used a false discovery rate approach to correct for multiple comparisons and compute q-values. We also compared incidence in clusters of cantons with similar agricultural characteristics (k-means algorithm). We identified 69,010 incident PD cases. Rurality was associated with higher PD incidence (p < 0.001). Cantons with higher density of vineyards displayed the strongest association (RR_{top/bottom quartile} = 1.102, 95% CI = 1.049–1.158; q-trend = 0.040). This association was similar in men, women, and non-farmers, stronger in older than younger persons, and present in all French regions. Persons living in the cluster with greatest vineyards density had 8.5% (4.4–12.6%) higher PD incidence (p < 0.001). In France, vineyards rank among the crops that require most intense pesticide use. Regions with greater presence of vineyards are characterized by higher PD risk; non-professional pesticides exposure is a possible explanation.     

Associations between B Vitamins and Parkinson’s Disease

B vitamins may correlate with Parkinson’s disease (PD) through regulating homocysteine level. However, there is no comprehensive assessment on the associations between PD and B vitamins. The present study was designed to perform a meta-analytic assessment of the associations between folate, vitamin B6, and vitamin B12 and PD, including the status of B vitamins in PD patients compared with controls, and associations of dietary intakes of B vitamins and risk of PD. A literature search using Medline database obtained 10 eligible studies included in the meta-analyses. Stata 12.0 statistical software was used to perform the meta-analysis. Pooled data revealed that there was no obvious difference in folate level between PD patients and healthy controls, and PD patients had lower level of vitamin B12 than controls. Available data suggested that higher dietary intake of vitamin B6 was associated with a decreased risk of PD (odds ratio (OR) = 0.65, 95% confidence intervals (CI) = (0.30, 1.01)), while no significant association was observed for dietary intake of folate and vitamin B12 and risk of PD. PD patients had lower level of vitamin B12 and similar level of folate compared with controls. Dietary intake of vitamin B6 exhibited preventive effect of developing PD based on the available data. As the number of included studies is limited, more studies are needed to confirm the findings and elucidate the underpinning underlying these associations.     

Systematic Review of the Prevalence and Incidence of Parkinson’s Disease in Asia

Background

Parkinson’s disease (PD) is a common neurodegenerative disorder in older people, and half of the world’s older population lives in Asia. However, the epidemiology of PD in Asian countries is poorly understood. This review assembles evidence on the prevalence and incidence of PD in Asian countries and identifies gaps in our present knowledge.

Methods

A systematic search of studies published from 1965 to October 2008 was conducted using MEDLINE and EMBASE. The selection criteria were defined a priori. Prevalence and incidence were standardized to the WHO World Standard Population 2000. Twenty-one original studies were selected for the review. Two studies that described the ethnic origin of participants and contained Asian populations were also included in the analysis.

Results

Excluding one study with questionably low prevalence and incidence, the remaining studies reported a standardized all-age prevalence of 51.3 to 176.9 per 100 000 in door-to-door surveys; prevalence in record-based studies ranged from 35.8 to 68.3 per 100 000. The standardized incidence rates were 8.7 per 100 000 person-years in door-to-door surveys and 6.7 to 8.3 per 100 000 person-years in record-based surveys.

Conclusions

The prevalence of PD in Asian countries was slightly lower than that in Western countries. However, comparison of incidence was difficult because of the small number of studies. Varying methodologies, diagnostic criteria, and case-finding strategies contributed to the considerable variation in the reported prevalence and incidence of PD.Key words: epidemiology, prevalence, incidence, Parkinson’s disease, Asia     

Development of the Integrated Parkinson’s Care Network (IPCN): using co-design to plan collaborative care for people with Parkinson’s disease

Background

Parkinson’s disease (PD) is a progressive neurological illness that impacts various aspects of life. Integration of medical and self-management in a collaborative approach to care is needed to enhance functioning and the quality of life of PD patients. In developing an integrated care program at a tertiary PD clinic, we used a co-design process to gather stakeholder input.

Methods

This is a cross-sectional mixed methods study using surveys and interviews. Patient and caregiver participants from the clinic completed two questionnaires to evaluate perceived receipt of self-management support (Patient Assessment of Care for Chronic Conditions) and activation for managing their health condition (Patient or Caregiver Activation Measure®). A subset of these participants and healthcare providers took part in semi-structured interviews. Survey data were described and tested for relationships between patient characteristics and questionnaire scores using Spearman’s rank-order correlation. Interviews were analyzed using conventional content analysis.

Results

Fifty-seven PD patients and thirty caregivers completed the questionnaires. Thirteen patients, six caregivers, and six healthcare providers were interviewed. 58% of participants were moderately to highly activated to manage their lives with PD. Participants’ perceptions of self-management support varied but was lacking in dimensions of goal-setting and follow-up support/coordination. Qualitative analysis revealed four overarching themes related to experiences of managing PD: activation, self-management support, coordinated care, and access to services.

Conclusions

This first study to explore patient activation in PD found high levels of activation but moderate to low levels of self-management support. The co-design process highlighted important aspects of a more collaborative approach to care.

     

Quality of life in Parkinson’s disease patients: validation of the Short-Form Eight-item Parkinson’s Disease Questionnaire (PDQ-8) in Taiwan

Purpose  

This study sought to evaluate the Chinese version of the eight-item Parkinson’s Disease Questionnaire (PDQ-8), through standard psychometric techniques.     

Dopamine Transporter Genetic Variants and Pesticides in Parkinson’s Disease

Background

Research suggests that independent and joint effects of genetic variability in the dopamine transporter (DAT) locus and pesticides may influence Parkinson’s disease (PD) risk.

Materials

Methods: In 324 incident PD patients and 334 population controls from our rural California case–control study, we genotyped rs2652510, rs2550956 (for the DAT 5′ clades), and the 3′ variable number of tandem repeats (VNTR). Using geographic information system methods, we determined residential exposure to agricultural maneb and paraquat applications. We also collected occupational pesticide use data. Employing logistic regression, we calculated odds ratios (ORs) for clade diplotypes, VNTR genotype, and number of susceptibility (A clade and 9-repeat) alleles and assessed susceptibility allele–pesticide interactions.

Results

PD risk was increased separately in DAT A clade diplotype carriers [AA vs. BB: OR = 1.66; 95% confidence interval (CI), 1.08–2.57] and 3′ VNTR 9/9 carriers (9/9 vs. 10/10: OR = 1.8; 95% CI, 0.96–3.57), and our data suggest a gene dosing effect. Importantly, high exposure to paraquat and maneb in carriers of one susceptibility allele increased PD risk 3-fold (OR = 2.99; 95% CI, 0.88–10.2), and in carriers of two or more alleles more than 4-fold (OR = 4.53; 95% CI, 1.70–12.1). We obtained similar results for occupational pesticide measures.

Discussion

Using two independent pesticide measures, we a) replicated previously reported gene–environment interactions between DAT genetic variants and occupational pesticide exposure in men and b) overcame previous limitations of nonspecific pesticide measures and potential recall bias by employing state records and computer models to estimate residential pesticide exposure.

Conclusion

Our results suggest that DAT genetic variability and pesticide exposure interact to increase PD risk.     

Association between time-related work factors and dietary behaviors: results from the Japan Environment and Children’s Study (JECS)

Background

Few studies have examined the association of workhours and shift work (referred to here as “time-related work factors”) with dietary behaviors. We aimed to investigate this association, as well as the dietary behaviors among individuals with occupations characterized by time-related work factors.

Methods

A cross-sectional study was performed using data from the Japan Environment and Children’s Study. The study included 39,315 working men. Dietary behaviors (i.e., skipping breakfast, eating out, eating instant food, overeating, and eating fast) were assessed with a self-reported information from the Food Frequency Questionnaire. Logistic regression analysis was conducted to examine the associations of time-related work factors with dietary behaviors and dietary behavior tendencies among those in occupations characterized by long workhours and/or shift work.

Results

Long workhours were associated with high frequencies of skipping breakfast, eating out, eating instant food, overeating, and eating fast. The frequency of having shift work was associated with high frequencies of skipping breakfast, eating out, and eating instant food. Several occupations involving long workhours and/or shift work showed specific dietary behaviors; in some occupations, the level of significance changed after adjusting for time-related work factors in addition to other potential confounding factors.

Conclusions

Time-related work factors may help explain workers’ dietary behaviors. Long workhours and shift work may lead to poor dietary behaviors. Other factors influenced by occupation itself, such as food environment, may also influence workers’ dietary behaviors. Workhours and/or shift work, and these other work factors, should be given attention in workplace health promotion.

     

Environmental Exposure,Obesity, and Parkinson’s Disease: Lessons from Fat and Old Worms

Background

A common link has been exposed, namely, that metal exposure plays a role in obesity and in Parkinson’s disease (PD). This link may help to elucidate mechanisms of neurotoxicity.

Objective

We reviewed the utility of the nematode, Caenorhabditis elegans, as a model organism to study neurodegeneration in obesity and Parkinson’s disease (PD), with an emphasis on the neurotransmitter, dopamine (DA).

Data sources

A PubMed literature search was performed using the terms “obesity” and any of the following: “C. elegans,” “central nervous system,” “neurodegeneration,” “heavy metals,” “dopamine” or “Parkinson’s disease.” We reviewed the identified studies, including others cited therein, to summarize the current evidence of neurodegeneration in obesity and PD, with an emphasis on studies carried out in C. elegans and environmental toxins in the etiology of both diseases.

Data extraction and data synthesis

Heavy metals and DA have both been linked to diet-induced obesity, which has led to the notion that the mechanism of environmentally induced neurodegeneration in PD may also apply to obesity. C. elegans has been instrumental in expanding our mechanism-based knowledge of PD, and this species is emerging as a good model of obesity. With well-established toxicity and neurogenetic assays, it is now feasible to explore the putative link between metal-and chemical-induced neurodegeneration.

Conclusions

One side effect of an aging population is an increase in the prevalence of obesity, metabolic disorders, and neurodegenerative orders, diseases that are likely to co-occur. Environmental toxins, especially heavy metals, may prove to be a previously neglected part of the puzzle.     

A Study of the Relationship between Health and Subjective Well-Being in Parkinson’s Disease Patients

ObjectivesGovernments are turning their attention to evidence on subjective measures of well-being to inform policy decisions. In the context of health, there is, therefore, growing interest in understanding how measures of health-related quality of life relate to subjective well-being and whether subjective well-being could provide a basis for resource allocation decisions in the future. This study investigates the relationship between health-related quality of life, as measured by the EuroQol five-dimensional (EQ-5D) questionnaire, and subjective well-being in Parkinson’s disease.MethodsA paper questionnaire including the EQ-5D questionnaire, four key subjective well-being questions taken from the Integrated Household Survey in England, and other demographic details was distributed to people with Parkinson’s disease in the United Kingdom. Responses were used to estimate multiple regression models explaining subjective well-being using the EQ-5D questionnaire index (UK weights), EQ-5D questionnaire dimensions and the visual analogue scale, and patients’ sociodemographic characteristics.ResultsA total of 199 responses were received. Combining visual analogue scale and EQ-5D questionnaire dimensions, especially anxiety/depression and, to a lesser extent, mobility, yielded the best-fitting models (adjusted R² range 0.36–0.53). Patients with Parkinson’s disease living in care homes report lower levels of subjective well-being than do those living alone. These effects are not captured by the health-related quality-of-life measures in the analysis.ConclusionsUsual health-related quality-of-life measures can partially explain different well-being dimensions, yet they fail to capture part of the broader impact of disease on subjective well-being. Further empirical research into the relationship between subjective well-being and the EQ-5D Parkinson’s disease longitudinally, and in different disease areas, is required, and further standardization of subjective well-being measures is recommended.