Finlay Dick

Environmental risk factors for parkinson's disease and parkinsonism : the geoparkinson study

Objective: To investigate the associations between Parkinson’s disease and other degenerative parkinsonian syndromes and environmental factors in five European countries. Methods: A case–control study of 959 prevalent cases of parkinsonism (767 with Parkinson’s disease) and 1989 controls in Scotland, Italy, Sweden, Romania and Malta was carried out. Cases were defined using the United Kingdom Parkinson’s Disease Society Brain Bank criteria, and those with drug-induced or vascular parkinsonism or dementia were excluded. Subjects completed an interviewer-administered questionnaire about lifetime occupational and hobby exposure to solvents, pesticides, iron, copper and manganese. Lifetime and average annual exposures were estimated blind to disease status using a job-exposure matrix modified by subjective exposure modelling. Results were analysed using multiple logistic regression, adjusting for age, sex, country, tobacco use, ever knocked unconscious and family history of Parkinson’s disease. Results: Adjusted logistic regression analyses showed significantly increased odds ratios for Parkinson’s disease/parkinsonism with an exposure–response relationship for pesticides (low vs no exposure, odds ratio (OR) = 1.13, 95% CI 0.82 to 1.57, high vs no exposure, OR = 1.41, 95% CI 1.06 to 1.88) and ever knocked unconscious (once vs never, OR = 1.35, 95% CI 1.09 to 1.68, more than once vs never, OR = 2.53, 95% CI 1.78 to 3.59). Hypnotic, anxiolytic or antidepressant drug use for more than 1 year and a family history of Parkinson’s disease showed significantly increased odds ratios. Tobacco use was protective (OR = 0.50, 95% CI 0.42 to 0.60). Analyses confined to subjects with Parkinson’s disease gave similar results. Conclusions: The association of pesticide exposure with Parkinson’s disease suggests a causative role. Repeated traumatic loss of consciousness is associated with increased risk.

A life-course approach to the aetiology of late-onset dementias

Substantial progress has been made in the understanding of the neurobiology of dementias, but comprehensive causal models are not available. Genetic and environmental factors probably interact to determine vulnerability to the dementias. The life-course approach to age-related diseases, when systematically applied to the dementias, provides opportunities to identify the nature and timing of environmental contributions. We discuss the relevance of the fetal origins of adult disease hypothesis to the dementias. Associations between the dementias (most often described as Alzheimers disease) and ischaemic heart disease, obesity, hypertension, hyperlipidaemia, and non-insulin-dependent diabetes mellitus are set against associations between dementias and childhood intelligence, low educational attainments, low socioeconomic status, occupation, and lifetime dietary history. Biological mechanisms that explain how fetal development might influence the risk of adult disease may be relevant to many age-related diseases including the dementias and, possibly, to the biology of ageing.

Gene‐environment interactions in parkinsonism and Parkinson's disease: the Geoparkinson study

Objectives: To investigate associations of Parkinson’s disease (PD) and parkinsonian syndromes with polymorphic genes that influence metabolism of either foreign chemical substances or dopamine and to seek evidence of gene-environment interaction effects that modify risk. Methods: A case-control study of 959 prevalent cases of parkinsonism (767 with PD) and 1989 controls across five European centres. Occupational hygienists estimated the average annual intensity of exposure to solvents, pesticides and metals, (iron, copper, manganese), blind to disease status. CYP2D6, PON1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, CYP1B1, MAO-A, MAO-B, SOD 2, EPHX, DAT1, DRD2 and NAT2 were genotyped. Results were analysed using multiple logistic regression adjusting for key confounders. Results: There was a modest but significant association between MAO-A polymorphism in males and disease risk (G vs T, OR 1.30, 95% CI 1.02 to 1.66, adjusted). The majority of gene-environment analyses did not show significant interaction effects. There were possible interaction effects between GSTM1 null genotype and solvent exposure (which were stronger when limited to PD cases only). Conclusions: Many small studies have reported associations between genetic polymorphisms and PD. Fewer have examined gene-environment interactions. This large study was sufficiently powered to examine these aspects. GSTM1 null subjects heavily exposed to solvents appear to be at increased risk of PD. There was insufficient evidence that the other gene-environment combinations investigated modified disease risk, suggesting they contribute little to the burden of PD.

Which agents cause reactive airways dysfunction syndrome (RADS)? A systematic review

AIM To identify those agents reported as being associated with reactive airways dysfunction syndrome (RADS). METHODS A systematic review was undertaken. Abstracts were screened and those selected reviewed against pre-determined diagnostic criteria for RADS. RESULTS Significant information gaps were identified for all measures of interest. In some articles, even the causative agent was not reported. The most commonly reported agents were chlorine (nine subjects), toluene di-isocyanate (TDI) (n = 6) and oxides of nitrogen (n = 5). Most exposures occurred in the workplace (n = 51) and affected men (60%). Dyspnoea (71%) and cough (65%) were the commonest symptoms. Median symptom duration was 13 months (interquartile range = 6.5-43.5) for RADS. CONCLUSIONS Although the most commonly reported agent associated with RADS was chlorine, the main finding of a general lack of adequate information on exposure, investigation and outcome suggests that to better explore RADS a more structured approach to gathering information is required. A minimum data set for reporting RADS cases is proposed.

Health effects of solvent exposure among dockyard painters: mortality and neuropsychological symptoms.

OBJECTIVES: To study mortality and prevalence of neuropsychological symptoms among a cohort of painters known to have been heavily exposed to organic solvents. METHODS: A mortality study of 1292 male painters who had worked in a dockyard in Scotland for > or = 1 year between 1950 and 1992 comprised a nested cross sectional study of 953 surviving painters from the cohort and 953 male non-painters randomly selected from the local population and a case-control study of those with high symptom scores. Mortality, symptoms, and risks associated with painting, adjusting for age, education, smoking, alcohol, and personality were measured. RESULTS: The proportional mortality ratio for all cancers was not increased significantly (110 (95% confidence interval (95% CI) 84 to 143), except for a possible excess of deaths from ischaemic heart disease (132, 105 to 164). Standardised mortality ratios were not significantly increased. Among the 260 surviving painters and 539 community controls who responded to the questionnaire there was a significant excess of symptoms among painters; adjusted relative risk (RR) increased significantly with increasing symptom score. These RRs suggested an exposure-response relation; for a high score (12-22) for all symptoms RR was 2.27 (1.20 to 4.30) for 1-4 years of exposure, 2.42 (1.18 to 4.95) for 5-9 years, 2.89 (1.42 to 5.88) for 10-14 years, and 3.41 (1.82 to 6.36) for 15-41 years, compared with controls. In multivariate analyses, painting exposure, and aging were associated with high symptom scores and there was again an increased risk relative to time worked as a painter. CONCLUSION: This study supports the hypothesis that heavy and prolonged exposure to paint solvents leads to neuropsychological ill health.

Impairment of colour vision in workers exposed to organic solvents

OBJECTIVES To investigate loss of colour vision related to exposure to solvents and the role of three enzyme polymorphisms in modifying the risk in exposed workers. METHODS A sample was studied of 68 male dockyard workers and 42 male community controls with and without neuropsychological symptoms from a previous cross sectional study. Indices of cumulative and intensity based exposure to solvents were calculated for all subjects. Alcohol, drug, and smoking histories were obtained. Colour vision was tested by Lanthony D15d colour vision test. Genotype of glutathione S-transferase M1 and T1 and N-acetyltransferase 2 polymorphisms were determined. RESULTS The relation between impairment of colour vision and exposure to solvents was investigated with multiple regression techniques. Increasing annual exposure to solvents was significantly associated with reduced colour vision (p=0.029). Impairment of colour vision was not associated with neuropsychological symptoms as measured by the Q16 solvent symptom questionnaire. No significant association was found between acquired impairment of colour vision and genetic polymorphisms when GSTM1, GSTT1 or NAT2 phenotypes were included in the analyses. CONCLUSIONS Exposure to mixed solvents is associated with impairment in colour vision, the risk increases with increasing exposure. The risk of impairment of colour vision was not altered in this study by the presence of different GSTM1, GSTT1 or NAT2 polymorphisms.

A case-control study of Parkinson’s disease and tobacco use : gene-tobacco interactions

A case‐control study of genetic, environmental, and occupational risk factors for Parkinsons disease (PD) was carried out in five European countries (Italy, Malta, Romania, Scotland, and Sweden) to explore the possible contribution of interactions among host and environmental factors in sporadic PD. Whereas smoking habits confirmed its negative association with PD, a possible modulatory role of genetic polymorphisms was investigated to obtain further mechanistic insights. We recruited 767 cases of PD and 1989 age‐matched and gender‐matched controls. Participants completed an interviewer‐administered questionnaire including the history of smoking habits. The polymorphisms of genes involved either in metabolism of compounds contained in tobacco smoke (CYP2D6, CYP1B1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, SOD2, EPHX and NAT2) or in dopaminergic neurotransmission (MAOA, MAOB, DAT1 and DRD2) were characterized by PCR based methods on genomic DNA. We found evidence of statistically significant gene‐tobacco interaction for GSTM1, NAT2, and GSTP1, the negative association between tobacco smoking and PD being significantly enhanced in subjects expressing GSTM1‐1 activity, in NAT2 fast acetylators, and in those with the GSTP1*B*C haplotype. Owing to the retrospective design of the study, these results require confirmation.

Workplace management of upper limb disorders: a systematic review

BACKGROUND Upper limb pain is common among working-aged adults and a frequent cause of absenteeism. AIMS To systematically review the evidence for workplace interventions in four common upper limb disorders. METHODS Systematic review of English articles using Medline, Embase, Cinahl, AMED, Physiotherapy Evidence Database PEDro (carpal tunnel syndrome and non-specific arm pain only) and Cochrane Library. Study inclusion criteria were randomized controlled trials, cohort studies or systematic reviews employing any workplace intervention for workers with carpal tunnel syndrome, non-specific arm pain, extensor tenosynovitis or lateral epicondylitis. Papers were selected by a single reviewer and appraised by two reviewers independently using methods based on Scottish Intercollegiate Guidelines Network (SIGN) methodology. RESULTS 1532 abstracts were identified, 28 papers critically appraised and four papers met the minimum quality standard (SIGN grading + or ++) for inclusion. There was limited evidence that computer keyboards with altered force displacement characteristics or altered geometry were effective in reducing carpal tunnel syndrome symptoms. There was limited, but high quality, evidence that multi-disciplinary rehabilitation for non-specific musculoskeletal arm pain was beneficial for those workers absent from work for at least four weeks. In adults with tenosynovitis there was limited evidence that modified computer keyboards were effective in reducing symptoms. There was a lack of high quality evidence to inform workplace management of lateral epicondylitis. CONCLUSIONS Further research is needed focusing on occupational management of upper limb disorders. Where evidence exists, workplace outcomes (e.g. successful return to pre-morbid employment; lost working days) are rarely addressed.

Nasal, eye, and skin irritation in dockyard painters

OBJECTIVES To determine whether the risk of irritant symptoms in painters is related to their exposure to paint. METHODS The prevalences of skin, eye and nasal symptoms were compared in 260 United Kingdom and 109 Chinese dockyard painters, 539 British community controls, and 255 Chinese dockyard controls, relative to their exposure to paints. RESULTS Painters showed an excess of irritant symptoms compared with controls. Adjusted relative risks (RRs) (95% confidence interval (95% CI) were: for skin irritation 1.58 (1.19 to 2.08) in British painters and 2.68 (1.73 to 4.09) in Chinese painters; for eye irritation, 1.41 (0.98 to 2.05) and 3.01 (1.90 to 4.76); and for nasal irritation, 1.53 (1.10 to 2.14) and 6.73 (3.53 to 12.82), respectively. Exposure duration-response relations were found for these symptoms; the risks decreased with time after exposure ended. CONCLUSIONS Irritant symptoms occur more often in dockyard painters than in controls, and this is likely to be a response to exposure to paint.

Development of a Task-Exposure Matrix (TEM) for pesticide use (TEMPEST).

INTRODUCTION Pesticides have been associated with increased risks for a range of conditions including Parkinsons disease, but identifying the agents responsible has proven challenging. Improved pesticide exposure estimates would increase the power of epidemiological studies to detect such an association if one exists. METHODS Categories of pesticide use were identified from the tasks reported in a previous community-based case-control study in Scotland. Typical pesticides used in each task in each decade were identified from published scientific and grey literature and from expert interviews, with the number of potential agents collapsed into 10 groups of pesticides. A pesticide usage database was then created, using the task list and the typical pesticide groups employed in those tasks across seven decades spanning the period 1945-2005. Information about the method of application and concentration of pesticides used in these tasks was then incorporated into the database. RESULTS A list was generated of 81 tasks involving pesticide exposure in Scotland covering seven decades producing a total of 846 task per pesticide per decade combinations. A Task-Exposure Matrix for PESTicides (TEMPEST) was produced by two occupational hygienists who quantified the likely probability and intensity of inhalation and dermal exposures for each pesticide group for a given use during each decade. CONCLUSIONS TEMPEST provides a basis for assessing exposures to specific pesticide groups in Scotland covering the period 1945-2005. The methods used to develop TEMPEST could be used in a retrospective assessment of occupational exposure to pesticides for Scottish epidemiological studies or adapted for use in other countries.