1. GRACE CHEN18 TH OCTOBER, 2014

2. OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURONE DISEASE IN NZ Case - Control Study

3. OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE Very little is known about the causes of Motor Neurone Disease. Our study is to investigate the relationship between MND in New Zealand and a range of known or suspected occupational and environmental exposures.

4. OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE This will be the first New Zealand study to investigate these potential risk factors, and it will allow comparisons to be made with MND in other developed countries.

5. WHAT IS MOTOR NEURON DISEASE The motor neuron diseases (MNDs) are a group of progressive neurological disorders that destroy motor neurons, the cells that control essential voluntary muscle activity such as upper and lower limb activities, speaking, breathing, and swallowing. OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE

6. BACKGROUND AND EPIDEMIOLOGY OF MND MND is uncommon but not rare and there is no cure or standard treatment for MND. Death usually results from respiratory failure and other lung complications, on average about 3 years after the first symptoms of weakness appear. Most MND cases are sporadic, familial ( inherited ) forms of MND account for less than 10% of cases. OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE

7. BACKGROUND AND EPIDEMIOLOGY OF MND Highest incidence at age 70 years MND is more common in males than females with a ratio of 3:2. There has been some evidence of increasing incidence and mortality rates in developed countries in the last two decades. OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE

8. BACKGROUND AND EPIDEMIOLOGY OF MND In New Zealand 300 cases in NZ at any one time (7/100,000 pa) 100 new cases each year (2/100,000 pa) Some evidence of increasing incidence in New Zealand Ageing population in NZ (New Zealand has an ageing population, with the proportion aged 65 years or older increasing from 11.8% to 13.1% during 2000- 2010) The ageing population and increasing incidence mean that the number of MND cases in New Zealand is expected to rise. OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE

9. POTENTIAL OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MND Occupational risk factors: Agricultural chemicals Electrical occupations/Electromagnetic fields (EMF)/ Electric shock Neurotoxic agents : solvents ， lead, mercury or other heavy metals Welding Fumigants : methyl bromide A range of chemicals in occupations: textile workers, veterinarians, hairdressers Military service OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE

10. POTENTIAL OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MND Environmental and other risk factors: Rural vs. urban residence Smoking Head trauma (history of head injury including sporting injuries) OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE

11. INTERNATIONAL STUDY - 1 - Pesticide exposure and MND A meta-analysis of epidemiological studies. Malek et al, 2012. A meta-analysis of 6 epidemiological studies published to 2011. Total 592 cases from 6 studies Result: exposure to pesticides had a risk of develop MND Summary OR=1.88, (95% CI 1.36 – 2.61) OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE

12. INTERNATIONAL STUDY - 2 - Chemical exposures and ALS American Cohort study: Weisskopf et al, 2009 over 1 million participants from American Cancer Society's Cancer Prevention Study II. Follow-up from 1989 through 2004 Individuals exposed to pesticides/herbicides compared to the unexposed identified 617 male and 539 female deaths from ALS Result *There was a strongly dose-response relation with increasing years of exposure. OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE ExposuresRR Pesticides/herbicides (excluding those with missing duration of pesticides exposure ) 1.44 ( 95% CI: 0.89-2.31) Formaldehyde1.34 ( 95% CI: 0.93-1.92)

13. INTERNATIONAL STUDY - 3 Workplace exposure and ALS American case control study, Fang, et al,2009 109 cases and 253 control (3 years) Compare detailed occupation and workplace exposure Result: OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE OccupationOR (95% CI) Precision metal workers3.5 (1.2-10.5) Construction workers2.9 (1.2-7.2)

14. INTERNATIONAL STUDY - 3 Workplace exposure and ALS continue… Self-reported exposures to : paint strippers; cooling, lubricating oils; antifreeze or coolants; mineral or white spirits; dry cleaning agents each exposure appeared to be associated with a 60–90% higher risk. OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE

15. INTERNATIONAL STUDY – 4 Head injury and ALS Oxford Record Linkage Study Turner et al, 2010. hospital records 1963 - 1999. Follow up all in-patients for head injury. ALS rate after head injury RR=1.5 (95% CI 1.1 – 2.1). Swedish Case and control study, Peters et al, 2013. 4004 Swedish cases and 20,020 controls. Conclusions: Similar finding of elevated ALS risk with severe head injury. OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE

16. INTERNATIONAL STUDY – 5 Smoking, alcohol consumption, and the risk of MND OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE Dutch Case-Control study. De Jong et al, 2012 494 cases, 1,599 controls. Results: Current smokers OR = 1.38, 95% CI 1.02 – 1.88. Current smoking also associated with shorter survival HR = 1.51, 95% CI 1.07 – 2.15. (HR= hazard risk) Current alcohol consumption is a protected factor. OR = 0.52, 95% CI 0.40 – 0.75. Conclusions: - Current smoking increases risk. - Alcohol consumption reduces risk

17. OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE “If MND had just one cause, researchers would have found it a long time ago”. Dr Brian Dickie Director of Research Development UK MND Association

18. NEW ZEALAND POPULATION BASED CASE- CONTROL STUDY The study will recruit 400 cases and 800 controls. Cases will be diagnosed for MND by neurologists and will be recruited directly from the Motor Neuron Disease Association New Zealand ( MNDANZ ) and/or neurologists throughout the country. Controls will be selected from the New Zealand Electoral Roll, with two controls for each case, matched for age and gender. The controls will thus be representative of the general population that generated the cases. OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE

19. NEW ZEALAND POPULATION BASED CASE- CONTROL STUDY The methods used to collect the data will be the same for both cases and controls face-to-face interviews telephone interviews postal questionnaires (depending on the preference of the participant). OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE

20. NEW ZEALAND POPULATION BASED CASE- CONTROL STUDY Standard questionnaire (16 parts) to obtain information on: –demographic details –residential history –lifestyle factors –complete occupational history –Agriculture questions OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE

21. NEW ZEALAND POPULATION BASED CASE- CONTROL STUDY Occupational exposure determined through use of Job Exposure Matrices Environmental exposure determined through EPA data on location of use of specific chemicals - linked to information on residence. OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE

22. NEW ZEALAND POPULATION BASED CASE- CONTROL STUDY Result to date For cases: 217 invitation letters have been sent. 199 replied (92%). Of those 199, 176 agreed to take part in the study 164 have been interviewed, 12 cases are in progress For Controls: 1600 invitation letters have been sent out, 814 replied (51%). Of those 814, 392 participated in the study. 245 have been interviewed, 147 are in progress. OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE

23. DETAILS OF CASES Total cases :176 112 Males 64 Females Male/Female ratio  3:2 Age group: 107 cases (61%) are in the age 60 -74  30 cases (17%) are in the age 60-64  44 cases (25%) are in the age 65-69  33 cases ( 19%) are in the age 70-74 11 cases are over 80 3 cases are under 40 OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE

24. CASES AGE GROUPS

25. CASES ACCORDING TO DHB

26. OCCUPATIONAL AND ENVIRONMENTAL RISK FACTORS FOR MOTOR NEURON DISEASE

29. Thank you for all your support