| 21. |
- Sieurin, Johanna, et al.
(författare)
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Occupational stress and risk for Parkinson's disease : A nationwide cohort study.
- 2018
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Ingår i: Movement Disorders. - : John Wiley & Sons Ltd. - 0885-3185 .- 1531-8257. ; 33:9, s. 1456-1464
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Stress has been suggested as a contributing factor in the etiology of Parkinson's Disease (PD), but epidemiological evidence is sparse.OBJECTIVE: The objective of this study was to explore the association between occupational stress according to the job demands-control model and the risk for PD.METHODS: We conducted a population-based cohort study with 2,544,748 Swedes born 1920 to 1950 who had an occupation reported in the population and housing censuses in 1980 or, if missing, in 1970. Job demands and control were measured using a job-exposure matrix. Incident PD cases were identified using Swedish national health registers from 1987 to 2010. Data were analyzed with Cox regression with age as the underlying time scale, adjusting for sex, education, and chronic obstructive pulmonary disease as a proxy for smoking.RESULTS: During a mean follow-up time of 21.3 years, 21,544 incident PD cases were identified. High demands were associated with increased PD risk among men, most evident in men with high education. High control was associated with increased PD risk among the low educated. This association was more pronounced in women. High-strain jobs (high demands and low control) was only associated with increased PDrisk among men with high education, whereas active jobs (high demands and high control) were associated with increased PD risk among men with low education.INTERPRETATION: High job demands appear to increase PD risk in men, especially in men with high education, whereas high job control increases PD risk among low educated, more strongly in women. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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| 22. |
- Song, Huan, et al.
(författare)
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Association of Stress-Related Disorders With Subsequent Neurodegenerative Diseases
- 2020
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Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 77:6, s. 700-709
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Posttraumatic stress disorder (PTSD) has been associated with increased risk for dementia. Less is known, however, about other stress-related disorders and their associations with neurodegenerative diseases.Objective: To examine the association between stress-related disorders and risk for neurodegenerative diseases.Design, Setting, and Participants: This population-matched and sibling cohort study was conducted in Sweden using data from nationwide health registers, including the Swedish National Patient Register. Individuals who received their first diagnosis of stress-related disorders between January 1, 1987, and December 31, 2008, were identified. Individuals who had a history of neurodegenerative diseases, had conflicting or missing information, had no data on family links, or were aged 40 years or younger at the end of the study were excluded. Individuals with stress-related disorders were compared with the general population in a matched cohort design; they were also compared with their siblings in a sibling cohort. Follow-up commenced from the age of 40 years or 5 years after the diagnosis of stress-related disorders, whichever came later, until the first diagnosis of a neurodegenerative disease, death, emigration, or the end of follow-up (December 31, 2013), whichever occurred first. Data analyses were performed from November 2018 to April 2019.Exposures: Diagnosis of stress-related disorders (PTSD, acute stress reaction, adjustment disorder, and other stress reactions).Main Outcomes and Measurements: Neurodegenerative diseases were identified through the National Patient Register and classified as primary or vascular. Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis were evaluated separately. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% CIs after controlling for multiple confounders.Results: The population-matched cohort included 61 748 exposed individuals and 595 335 matched unexposed individuals. A total of 44 839 exposed individuals and their 78 482 unaffected full siblings were included in the sibling cohort analysis. The median (interquartile range) age at the start of follow-up was 47 (41-56) years, and 24 323 (39.4%) of the exposed individuals were male. The median (interquartile range) follow-up was 4.7 (2.1-9.8) years. Compared with unexposed individuals, individuals with a stress-related disorder were at an increased risk of neurodegenerative diseases (HR, 1.57; 95% CI, 1.43-1.73). The risk increase was greater for vascular neurodegenerative diseases (HR, 1.80; 95% CI, 1.40-2.31) than for primary neurodegenerative diseases (HR, 1.31; 95% CI, 1.15-1.48). A statistically significant association was found for Alzheimer disease (HR, 1.36; 95% CI, 1.12-1.67) but not Parkinson disease (HR, 1.20; 95% CI, 0.98-1.47) or amyotrophic lateral sclerosis (HR, 1.20; 95% CI, 0.74-1.96). Results from the sibling cohort corroborated results from the population-matched cohort.Conclusions and Relevance: This study showed an association between stress-related disorders and an increased risk of neurodegenerative diseases. The relative strength of this association for vascular neurodegenerative diseases suggests a potential cerebrovascular pathway.
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| 23. |
- Sun, Jiangwei, et al.
(författare)
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Gastrointestinal biopsy of normal mucosa or nonspecific inflammation and risk of neurodegenerative disease : Nationwide matched cohort study
- 2023
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Ingår i: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 30:11, s. 3430-3439
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Evidence has accumulated to support the early involvement of altered gastrointestinal (GI) function in neurodegenerative disease. However, risk of Alzheimer disease (AD) and Parkinson disease (PD) among individuals with a GI biopsy of normal mucosa or nonspecific inflammation is unknown.Methods: This matched cohort study included all individuals in Sweden with a GI biopsy of normal mucosa (n = 480,346) or nonspecific inflammation (n = 655,937) during 1965-2016 (exposed group) as well as their individually matched population references and unexposed full siblings. A flexible parametric model and stratified Cox model were used to estimate hazard ratio (HR) and its 95% confidence interval (CI).Results: Individuals with normal mucosa or nonspecific inflammation had a higher risk of AD and PD during the 20 years after biopsy. Compared with the population references, individuals with normal mucosa had an increased risk of AD (incidence rate [IR] difference = 13.53 per 100,000 person-years, HR [95% CI] = 1.15 [1.11-1.20]) and PD (IR difference = 6.72, HR [95% CI] = 1.16 [1.10-1.23]). Elevated risk was also observed for nonspecific inflammation regarding AD (IR difference = 13.28, HR [95% CI] = 1.11 [1.08-1.14]) and PD (IR difference = 6.83, HR [95% CI] = 1.10 [1.06-1.14]). Similar results were observed in subgroup and sensitivity analyses and when comparing with their unexposed siblings.Conclusions: Individuals with a GI biopsy of normal mucosa or nonspecific inflammation had an increased risk of AD and PD. This adds new evidence of the early involvement of GI dysfunction in neurodegenerative disease.
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| 24. |
- Sun, Jiangwei, et al.
(författare)
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Hospital-treated infections in early- and mid-life and risk of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis : A nationwide nested case-control study in Sweden
- 2022
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Ingår i: PLoS Medicine. - : Public Library of Science. - 1549-1277 .- 1549-1676. ; 19:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Experimental observations have suggested a role of infection in the etiology of neurodegenerative disease. In human studies, however, it is difficult to disentangle whether infection is a risk factor or rather a comorbidity or secondary event of neurodegenerative disease. To this end, we examined the risk of 3 most common neurodegenerative diseases in relation to previous inpatient or outpatient episodes of hospital-treated infections.Methods and findings: We performed a nested case-control study based on several national registers in Sweden. Cases were individuals newly diagnosed with Alzheimer's disease (AD), Parkinson's disease (PD), or amyotrophic lateral sclerosis (ALS) during 1970 to 2016 in Sweden, identified from the National Patient Register. For each case, 5 controls individually matched to the case on sex and year of birth were randomly selected from the general population. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) with adjustment for potential confounders, including sex, year of birth, area of residence, educational attainment, family history of neurodegenerative disease, and Charlson comorbidity index. Infections experienced within 5 years before diagnosis of neurodegenerative disease were excluded to reduce the influence of surveillance bias and reverse causation. The analysis included 291,941 AD cases (median age at diagnosis: 76.2 years; male: 46.6%), 103,919 PD cases (74.3; 55.1%), and 10,161 ALS cases (69.3; 56.8%). A hospital-treated infection 5 or more years earlier was associated with an increased risk of AD (OR = 1.16, 95% CI: 1.15 to 1.18, P < 0.001) and PD (OR = 1.04, 95% CI: 1.02 to 1.06, P < 0.001). Similar results were observed for bacterial, viral, and other infections and among different sites of infection including gastrointestinal and genitourinary infections. Multiple infections before age 40 conveyed the greatest risk of AD (OR = 2.62, 95% CI: 2.52 to 2.72, P < 0.001) and PD (OR = 1.41, 95% CI: 1.29 to 1.53, P < 0.001). The associations were primarily due to AD and PD diagnosed before 60 years (OR = 1.93, 95% CI: 1.89 to 1.98 for AD, P < 0.001; OR = 1.29, 95% CI: 1.22 to 1.36 for PD, P < 0.001), whereas no association was found for those diagnosed at 60 years or older (OR = 1.00, 95% CI: 0.98 to 1.01 for AD, P = 0.508; OR = 1.01, 95% CI: 0.99 to 1.03 for PD, P = 0.382). No association was observed for ALS (OR = 0.97, 95% CI: 0.92 to 1.03, P = 0.384), regardless of age at diagnosis. Excluding infections experienced within 10 years before diagnosis of neurodegenerative disease confirmed these findings. Study limitations include the potential misclassification of hospital-treated infections and neurodegenerative diseases due to incomplete coverage of the National Patient Register, as well as the residual confounding from unmeasured risk or protective factors for neurodegenerative diseases.Conclusions: Hospital-treated infections, especially in early- and mid-life, were associated with an increased risk of AD and PD, primarily among AD and PD cases diagnosed before 60 years. These findings suggest that infectious events may be a trigger or amplifier of a preexisting disease process, leading to clinical onset of neurodegenerative disease at a relatively early age. However, due to the observational nature of the study, these results do not formally prove a causal link.
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| 25. |
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| 26. |
- Wirdefeldt, Karin, et al.
(författare)
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Complete ascertainment of Parkinson disease in the Swedish Twin Registry
- 2008
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 29:12, s. 1765-1773
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Tidskriftsartikel (refereegranskat)abstract
- This report describes the ascertainment of Parkinson disease (PD) in all individuals aged 50 years or older (49,814 individuals) from the Swedish Twin Registry. In phase one of the study, all twins were screened for PD using telephone interviews, with a response rate of 72.7%. In phase two, twins with suspected PD were re-contacted to exclude anyone from follow-up who reported parkinsonian symptoms due to diseases other than PD. In the third phase, in-person clinical evaluations were completed for twins who were still considered PD suspects after phase two and for a sample of co-twins. During the clinical evaluations, we also collected blood samples and information about a variety of environmental exposures. Overall prevalence rate for PD was 496 per 100,000 individuals. Among the 132 PD cases identified, there were only three concordant twin pairs. In total 7.2% of PD cases reported a first degree relative with PD.
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| 27. |
- Wirdefeldt, Karin, et al.
(författare)
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Levodopa–Carbidopa Intestinal Gel in Patients with Parkinson’s Disease : A Systematic Review
- 2016
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Ingår i: CNS Drugs. - : Springer Science and Business Media LLC. - 1172-7047 .- 1179-1934. ; 30:5, s. 381-404
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Forskningsöversikt (refereegranskat)abstract
- Background Levodopa-carbidopa intestinal gel (LCIG) is available in several countries for the treatment of advanced levodopa-responsive Parkinson's disease (PD) with severe motor fluctuations and dyskinesia when other treatments have not given satisfactory results. Objective Our objective was to summarize the present evidence base for LCIG therapy through a systematic review of the literature. Methods Studies were identified from the PubMed and EMBASE databases up to 12 March 2016 using the following search terms: Parkinson disease, duodopa, levodopa/carbidopa intestinal gel, levodopa-carbidopa intestinal gel, LCIG, l-dopa infusion, levodopa infusion, duodenal l-dopa infusion, and duodenal levodopa infusion. Data extraction focused on whether LCIG therapy improves motor and non-motor outcomes as well as quality of life in PD patients compared with conventional therapy, apomorphine infusion, or deep brain stimulation. Randomized controlled trials (RCTs) and observational studies, with or without a control group, that included more than ten patients were included. The search was limited to peer-reviewed articles published in full in the English language and involving humans. Results Infusion of LCIG reduced "off'' time, increased "on'' time without increasing troublesome dyskinesias, and improved quality of life in three RCTs (one double-blind). Open-label follow-ups confirm these findings. The data evaluating long-term efficacy and safety are still limited. Conclusions The quality of evidence that LCIG is effective in reducing fluctuating motor symptoms and improving quality of life is moderate. Quality of evidence for reduction of non-motor symptoms is very low. Safety issues mainly relate to the intestinal infusion system. LCIG might be a useful treatment option in PD patients with severe motor fluctuations.
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| 28. |
- Wirdefeldt, Karin
(författare)
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Studies of genetic and environmental influences on Parkinson’s disease
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Little is known about the etiology of PD. Although several PD genes are known, these are thought to be involved in only a small proportion of all PD cases. Some environmental exposures are associated with PD, but there are few consistent findings. The overall aim of this thesis was to examine genetic and environmental factors of importance for PD. In 12 families with autosomal dominant PD, linkage analyses were performed for 11 candidate loci associated with inherited diseases with clinical symptoms similar to PD or coding for proteins whose function might suggest involvement in the disease mechanism. Parametric lod scores were negative and non-parametric lod scores were close to zero. Nine of the 11 loci were excluded under an autosomal dominant model with reduced penetrance. There was no evidence for linkage to the examined loci considering the non-parametric results, although linkage could not be excluded. A few families showed positive lod scores indicating possible genetic heterogeneity. a-Synuclein was the first gene genetically linked to PD. In cerebral cortex from eight patients with Lewy body disease and nine controls, the expression of a-Synuclein was assessed using mRNA in situ hybridization. The a-Synuclein probe labeled pyramidal-like cells in lamina III and V in both patients and controls. There was no difference in a-Synuclein mRNA levels between patients and controls, and among patients there was no relationship between a-Synuclein mRNA and number of Lewy bodies. Thus, up regulation of the a-Synuclein gene alone does not seem to explain the accumulation of the protein in Lewy bodies. Heritability of PD was evaluated using the Swedish Twin Registry. PD cases were identified through telephone interviews and the Inpatient Discharge Register. In total 247 twins with self-reported PD or a PD diagnosis in the Inpatient Discharge Register were identified. There were only two concordant pairs. Thus, environmental factors appear to be most important in the etiology of clinically diagnosed PD. In a co-twin control study that controls for confounding by genetic and familial environmental factors, the association between smoking and PD was evaluated. Exposure information was obtained prospectively and PD cases (N=476) were identified through the Inpatient Discharge Register and the Cause of Death Register. When controlling for alcohol, coffee and education there was an inverse association between smoking and PD using unrelated controls as well as co-twin controls. Thus, the protective effect of smoking on PD was confirmed. The association does not appear to be explained solely by genetic and familial environmental factors. This thesis highlights the fact that PD most likely is influenced by various genetic and environmental factors. The failure to demonstrate linkage to any of the candidate loci in the PD families indicates that other genes may be involved. As shown by the twin data, environmental factors are most important for sporadic PD. Exploring interactions between genetic and environmental factors represents a challenge in future studies of PD.
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| 29. |
- Yang, Fei, et al.
(författare)
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Dietary antioxidants and risk of Parkinson's disease in two population-based cohorts.
- 2017
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 32:11, s. 1631-1636
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A neuroprotective effect of dietary antioxidants on Parkinson's disease (PD) risk has been suggested, but epidemiological evidence is limited.OBJECTIVES: To examine the associations between intake of dietary antioxidant vitamins and total antioxidant capacity and risk of PD.METHODS: We prospectively assessed the relationships of dietary antioxidant vitamins C and E, ß-carotene, and total antioxidant capacity with PD risk in two population-based cohorts (38,937 women and 45,837 men).RESULTS: During a mean 14.9-year follow-up period, 1,329 PD cases were identified. Dietary intake of ß-carotene was associated with a lower risk of PD (hazard ratio: 0.86; 95% confidence interval: 0.78-0.95; Ptrend < 0.01 for women and hazard ratio: 0.91; 95% confidence interval: 0.84-0.99; Ptrend = 0.05 for men). An inverse association between dietary vitamin E and PD risk was found in women (hazard ratio: 0.87; 95% confidence interval: 0.79-0.96; Ptrend = 0.02). Dietary intake of vitamin C was inversely associated with PD risk in women at borderline significance (hazard ratio: 0.91; 95% confidence interval: 0.83-1.00; Ptrend = 0.04). There was no association between dietary total antioxidant capacity and PD risk in either women (hazard ratio: 0.93; 95% confidence interval: 0.84-1.02; Ptrend = 0.35) or men (hazard ratio: 1.00; 95% confidence interval: 0.93-1.07; Ptrend = 0.97).CONCLUSION: Intake of dietary vitamin E and ß-carotene was associated with a lower risk of PD. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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| 30. |
- Yang, Fei, et al.
(författare)
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Moist smokeless tobacco (Snus) use and risk of Parkinson's disease
- 2017
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 46:3, s. 872-880
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cigarette smoking is associated with a lower risk of Parkinson's disease. It is unclear what constituent of tobacco smoke may lower the risk. Use of Swedish moist smokeless tobacco (snus) can serve as a model to disentangle what constituent of tobacco smoke may lower the risk. The aim of this study was to determine whether snus use was associated with a lower risk of Parkinson's disease.METHODS: Individual participant data were collected from seven prospective cohort studies, including 348 601 men. We used survival analysis with multivariable Cox regression to estimate study-specific relative risk of Parkinson's disease due to snus use, and random-effects models to pool estimates in a meta-analysis. The primary analyses were restricted to never-smokers to eliminate the potential confounding effect of tobacco smoking.RESULTS: During a mean follow-up time of 16.1 years, 1199 incident Parkinson's disease cases were identified. Among men who never smoked, ever-snus users had about 60% lower Parkinson's disease risk compared with never-snus users [pooled hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.28-0.61]. The inverse association between snus use and Parkinson's disease risk was more pronounced in current (pooled HR 0.38, 95% CI 0.23-0.63), moderate-heavy amount (pooled HR 0.41, 95% CI 0.19-0.90) and long-term snus users (pooled HR 0.44, 95% CI 0.24-0.83).CONCLUSIONS: Non-smoking men who used snus had a substantially lower risk of Parkinson's disease. Results also indicated an inverse dose-response relationship between snus use and Parkinson's disease risk. Our findings suggest that nicotine or other components of tobacco leaves may influence the development of Parkinson's disease.
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