Epidemiology of Epidemiology of Parkinson’s DiseaseParkinson’s Disease

Kelly Sullivan, MSPHAssociate of Research

Parkinson’s Disease and Movement Disorders Center

Department of NeurologyUniversity of South Florida

Importance of EpidemiologyImportance of Epidemiology

Health care and planning Tool for investigation of the cause of PD

Defining disease characteristics such as prevalence, incidence, and mortality

Origins of Parkinson’sOrigins 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

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

Estimated 1 million patients in US Second most common age-related neurodegenerative disorder Second in frequency only to Alzheimer’s disease World-wide estimates vary

15/100,000 in China 657/100,000 in Argentina 100 - 250/100,000 in North America and Europe

Prevalence is predicted to triple over the next 50 years as average age of population increases.

PrevalencePrevalenceHow many people have PD?How many people have PD?

Incidence 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

IncidenceIncidenceDifficult to know how many people are diagnosed each year: Symptoms may develop and progress slowly Diagnostic criteria may vary Patient populations vary with respect to doctor visits

IncidenceIncidence

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

AgeAge

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

AgeAge

Prevalence increases with age from age 50-90

Affects 0.3% of general US population Affects 3% of those older than 65 Aging alone does not cause PD May increase susceptibility to other

factors or allow them to be expressed

GenderGender

Slightly more common in men than in women

Estimated 12-15 men for every 10 women

EthnicityEthnicity

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

EthnicityEthnicity 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 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 stronger diagnostic criteria

EthnicityEthnicity

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

EthnicityEthnicity

Differences in findings Suggest environmental factors more important than racial factors Further studies needed

Other factors? Differences in access to healthcare?

EthnicityEthnicity 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.

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

TimeTime

Hard to evaluate Few studies that track over long period of time Studies might use different methods or have different diagnostic criteria Two studies different conclusions Greater awareness - well-known people have developed PD

TimeTime

Study in Olmsted County, Minnesota1935-1988

Tracked number of people diagnosed with PD each year 1935-1944: 9.2/100,000 diagnosed 1975-1984: 16.3/100,000 diagnosed

TimeTime

NIH study of world-wide PD trends Statistically controlled for age differences Concluded that the prevalence and incidence of PD appear to have remained unchanged over the past 40 years

CausesCauses

The cause of Parkinson’s disease is unknown.

Many researchers believe that several factors combined are involved: free radicals, accelerated aging, environmental toxins, and genetic predisposition.

What Causes Parkinson's?What Causes Parkinson's? Why an individual develops Parkinson's disease

remains unclear. The cause is probably a combination of genetic

and environmental factors, and may vary from person to person.

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.

Risk Factors and Risk Factors and Protective FactorsProtective Factors

The single biggest risk factor for PD is advancing age Men have a slightly elevated risk compared to women 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

Risk Factors and Risk Factors and Protective FactorsProtective 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

Risk FactorsRisk FactorsEnvironmentEnvironment

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

Environmental FactorsEnvironmental Factors

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

Rural LivingRural 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

Environmental ToxinsEnvironmental 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

Environmental ToxinsEnvironmental 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

Genetics and PathogenesisGenetics 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

GeneticsGenetics 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

GeneticsGenetics 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

GeneticsGenetics 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

GeneticsGenetics 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

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

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

PD and Genetic TestingPD 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

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

PD Genetics and the FuturePD 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