1. Epidemiology of Parkinson’s Disease Julián Benito-León, MD, PhD Department of Neurology University Hospital “12 de Octubre” Madrid, Spain

2. Importance of Epidemiology Health care and planning Tool for investigation of the etiology and risk factors for PD Defining disease characteristics such as prevalence, incidence, and mortality

3. Origins of Parkinson’s Parkinson's disease was first formally described in "An Essay on the Shaking Palsy," published in 1817 by a London physician named James Parkinson It has probably existed for many thousands of years

4. Origins of Parkinson’s Symptoms and potential therapies mentioned in: Ayurveda, the system of medicine practiced in India as early as 5000 BC First Chinese medical text, Nei Jing, which appeared 2500 years ago

5. Prevalence How many people have PD? Estimated 1 million patients in US Second most common age-related neurodegenerative disorder Second in frequency only to Alzheimer’s disease

6. Prevalence How many people have PD? World-wide estimates vary 15/100,000 in China 657/100,000 in Argentina 100 - 250/100,000 in North America and Europe The prevalence figures of PD in Africa appeared lower than those reported for European and North American populations.

9. PD compared to other neurological diseases (Neurological Disorders in Central Spain) Fuente: Díaz-Guzmán J, Bermejo-Pareja F, Benito-León, J, et al. Neuroepidemiology (en evaluación). Fuente: Benito-León, J, Bermejo-Pareja F, Rodríguez J, et al. Mov Disord 2003;18:267-274. Fuente: Bermejo-Pareja F, Benito-León, Vega S, et al. Neuroepidemiology (en evaluación). Fuente: Benito-León, J, Bermejo-Pareja F, Morales JM, et al. Mov Disord 2003;18:389-394. Prevalence: – Dementia: 5.8% (95% IC 3.7-6.2) – Essential tremor: 4.8% (95% IC 4.2-5.4) – Stroke: 3.5% (95% IC 3.1- 4.0) – TIA: 1.3% (95% IC 1.1-1.7) – Parkinsonism: 2.2% (95% IC, 1.8-2.6) – Parkinson’s disease: 1.5% (95% IC, 1.2-1.8)

10. Incidence Quantifies the number of individuals who are newly diagnosed with PD in a given time period Unaffected by factors affecting disease survival

11. Incidence Quantifies the number of individuals who are newly diagnosed with PD in a given time period Unaffected by factors affecting disease survival Accurate measurements of the incidence of PD are relatively difficult Clinical manifestations of PD may be preceded by a long latent stage and have a slow clinical progression

12. Incidence Difficult to know how many people are diagnosed each year: Symptoms may develop and progress slowly Diagnostic criteria may vary

13. Incidence China: 1.5/100,000 Finland: 14.8/100,000 US: 20/100,000 Variations may be due to different diagnostic criteria and methods of case ascertainment in studies Lifetime risk of PD: 1 in 40

14. Incidence

15. Role of age, gender, and ethnicity

16. Age The incidence of PD increases with age Symptoms of Parkinson’s disease may appear at any age The median age of onset for idiopathic PD is 62.4 years Onset before age 30 is rare, but up to 10% of cases of idiopathic PD begin by age 40

17. Age Prevalence and incidence increases with age from age 50-90 Affects 0.3% of general US population Aging alone does not cause PD May increase susceptibility to other factors or allow them to be expressed

18. Gender Slightly more common in men than in women Estimated 12-15 men for every 10 women

19. Ethnicity Present worldwide, in all populations No region found to be free of PD More common in white people in Europe and North America (100-350/100,000) Lower rates in China, Nigeria and Sardinia The disorder occurs in all races but is somewhat more prevalent among Caucasians

20. Ethnicity Generally less common among African- Americans and Asians one-fifth to one-tenth as prevalent as in whites In Africa less common among blacks than whites

21. Ethnicity Door-to-door screening in Mississippi PD prevalence was not significantly different in whites and blacks after adjusting for age differences (poor diagnostic criteria) Higher prevalence in whites with strict diagnostic criteria

22. Ethnicity Two other studies conducted PD incidence in African-Americans and in Asian- Americans was similar to rates for European- Americans Door-to-door survey in Taiwan Prevalence of PD =119/100,000 Similar to that of a white population and much higher than that of previous studies of Asian populations

23. Ethnicity Differences in findings Suggest environmental factors more important than racial factors Further studies needed Other factors? Differences in access to healthcare?

24. Ethnicity The disease was once thought to affect primarily whites, but recent studies have demonstrated equal prevalence in African Americans and whites living in the same geographic area. Retrospective epidemiologic studies performed in various major cities have yielded contradictory information.

25. Ethnicity Variations in the prevalence of the disease in individual racial groups in different geographic areas have suggested an increased risk associated with rural living.

26. Causes The cause of Parkinson’s disease is unknown. Many researchers believe that several factors combined are involved: free radicals, accelerated ageing, environmental toxins, and genetic predisposition.

27. What Causes Parkinson's? The cause is probably a combination of genetic and environmental factors, and may vary from person to person.

28. What Causes Parkinson's? Although the cause of Parkinson's remains unknown, scientists have identified factors that contribute to Parkinson's in some patients. – People over age 60 have a two-to-four percent risk of developing Parkinson's disease, compared with the one-to-two percent risk in the general population.

29. Risk Factors and Protective Factors The single biggest risk factor for PD is advancing age Men have a slightly elevated risk compared to women

30. Risk Factors and Protective Factors Family history is also an important risk factor Individuals with an affected first-degree relative are estimated to have an approximately doubled risk for developing PD This increase cannot be explained by presence of any of the known genetic causes of PD, which together account for only a small percentage of familial cases

31. Risk Factors and Protective Factors Caffeine consumption is associated with a reduced incidence of PD Cigarette smoking has been associated with a reduced risk of PD It is not known whether smoking confers a genuine protective effect, or whether individuals who are prone to develop PD for other reasons are also prone to avoid smoking Nonetheless, the negative impact on general health from smoking is enormous, far in excess of any slight reduction in risk for PD Smoking cannot be recommended as a strategy for avoiding PD

32. Risk Factors Environment Environmental factors may play a role in PD Several members of some families with widely different ages developed PD within a short period of time The vast majority of cases of PD are thought to be due to the potential interactions of genes and the environment

33. Environmental Factors Factors include: physical trauma, exposure to chemicals and infections, and nutrition

34. Rural Living A strong and consistent finding is that the risk of PD is increased by: – rural living – exposure to well water – agricultural work Suggests that pesticides and/or herbicides may cause or contribute to PD

35. Environmental Toxins These conclusions are strengthened by several identified toxins that induce parkinsonism in animal models, and even in humans MPTP - originally identified as a contaminant in a batch of "street heroin" in Berkeley, California in the 1980s – Addicts who injected it developed a clinical syndrome almost identical to PD

36. Environmental Toxins The identification of MPTP led to much productive work on the cellular pathogenesis of PD However, numerous toxicological studies have demonstrated that MPTP itself is extremely rare in the environment, and thus is not a significant contributor to idiopathic PD It remains to be seen if any single agent will eventually be shown to account for more than a small fraction of PD cases

37. Genetics and Pathogenesis While the known genes for PD are responsible for only a minority of cases, they have provided extraordinary insight into the molecular pathology of the disease

38. Genetics Roughly one-fifth of Parkinson's disease patients have at least one relative with parkinsonian symptoms Suggests that a genetic factor may be involved Several genes that cause symptoms in younger patients have been identified Most researchers believe, however, that most cases are not caused by genetic factors alone

39. Genetics Genetic research studies over the past seven years have uncovered a total of 10 genes associated with PD For most cases of PD, however, these genes are not thought to play a role Small as their role may be, genes provide a crucial opportunity for us to study how the brain works

40. Genetics Because most patients do not have a clear history of either familial or environmental risk factors, the disorder may be due to a combination of genetic and environmental "influences" or "causes" In a small number of cases worldwide there is a strong inheritance pattern A genetic predisposition for Parkinson’s disease is possible, with the onset of disease and its gradual development dependant on a trigger, such as trauma, other illness, or exposure to an environmental toxin

41. Genetics In large epidemiological studies, researchers have found that people with an affected first-degree relative, such as a parent or sibling, have a two- to-three fold increased risk of developing Parkinson's, as compared to the general population

42. Genetics The vast majority of Parkinson's cases are not directly inherited, but researchers have discovered several genes that can cause the disease in a small number of families

43. Genetics Because genetic forms of a disease can be studied in great detail in the laboratory, and because understanding the rare genetic forms of Parkinson's disease may help to understand more common forms of the disease, genetic aspects of PD are currently the subject of intense research

44. PD and Genetic Testing Genetic testing in the general PD population - at the current stage of scientific knowledge - is not going to be helpful Researchers are still trying to determine which genetic factors contribute to the development of PD for the average patient

45. PD and Genetic Testing This is a very challenging task because we suspect that the interaction of genes with each other and with the environment is probably unique to each individual Until we gain this level of knowledge, we are a long way off from being able to offer the public PD genetic testing and accurate risk information for family members

46. PD Genetics and the Future The recent identification of genes that cause PD in a small group of PD families is helping us to understand the processes that lead to the development of PD Future research will undoubtedly reveal additional PD-associated genes and susceptibility factors, which will help us to further understand the cause of PD and lead to better diagnosis and treatment

47. Merci beaucoup!