Risk Factors and Protective Factors

The single biggest risk factor for PD is advancing age. Men have a slightly higher risk compared to women. Family history is also an important risk factor. Individuals with an affected first-degree relative (parent or sibling) are estimated to have an approximately doubled risk for developing PD. This increased risk is likely to be a combination of environmental and genetic factors that close relations have on common.

The single factor that has been most consistently associated with a reduced risk of PD is cigarette smoking, which has been demonstrated in numerous studies. 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.

Caffeine consumption is also associated with a reduced incidence of PD. In women, hormone replacement therapy appears to be associated with a reduced incidence in women who consume only small quantities of caffeine, but may be a risk factor in those who consume more than five cups per day.

Environmental Causes of PD

The vast majority of cases of PD are thought to be due to the potential interactions of genes and the environment. Environmental causes are presumed to be one or more widely present but weak toxins. The effects of these toxins may build up over time and eventually lead to disease in genetically predisposed individuals. The identity of these toxins is unknown, although several environmental risk factors have been identified through epidemiological studies.

A strong and consistent finding is that the risk of PD is increased by rural living, exposure to well water, and agricultural work, suggesting that pesticides or herbicides may cause or contribute to PD. It should be pointed out, however, that these individual factors do not by any means guarantee the development of PD, nor does their absence protect against it; there are many cases of individuals with none of these risk factors who develop PD, and many with them who do not.

Genetics

Defects in or mutations of several genes are known to cause PD, but these mutations actually result in only a very small number of cases of PD. The two most important genes are called parkin and LRRK2 (pronounced lark 2).

The parkin gene is responsible for making a protein, which is also called parkin. The job of the parkin protein in our bodies is to break down other proteins in brain cells that are damaged or defective. When the parkin gene is changed, or mutated, the parkin protein is not able to break down the damaged proteins. Some scientists think that, when the number of defective proteins builds up to a certain point, the brain cells in that part of the brain die. The death of these brain cells leads to the symptoms of PD.

We all have two copies of every gene in our bodiesone that was passed on to us from our mothers and one from our fathers. People who have PD that is caused by a problem with parkin have mutated copies of the parkin gene from both of their parents. This type of inheritance pattern is called "autosomal recessive." Parkin mutations cause young-onset PD, meaning that symptoms usually begin in people who are about 40 to 50 years old. Mutations of the parkin gene cause less than 1% of all cases of PD.

No one knows with certainty what the job of the LRRK2 gene is. Scientists do know, however, that people may develop PD who have only one mutated copy of LRRK2, inherited from either the mother or the father. This type of inheritance pattern is called autosomal dominant. LRRK2 mutations cause typical late-onset PD, meaning that the PD usually first starts in people who are 60 years of age or older. LRRK2 mutations are responsible for between one percent and six percent of late-onset PD. In some specific groups of people, however, the mutations are responsible for causing much higher percentages of cases of PD. In Ashkenazi Jews, approximately 20% of all PD may be due to LRRK2 mutations. In North African Arabs, the mutation may be the cause of up to 40% of cases of PD.

Other genes that, when mutated, are known to cause PD include alpha-synuclein, DJ-1, PINK-1, and UCHL-1. Even taken all together, however, these mutations cause only a small number of cases of PD.

Updated 10/25/06