Parkinson’s disease (PD) is one of the most common neurological disorders and the most common neurodegenerative disease in the world. The pathophysiology of Parkinson’s disease is quite well understood, albeit not completely. Dopaminergic neurons particularly in the substantia nigra, a part of the brain, becomes damaged gradually and die leading to lower than normal levels of the brain hormone dopamine.
Although this is known, the exact cause of this damage and cell death is not clearly understood. Risk factors including certain genetic mutations have been identified. However, these risks account for only a small proportion of PD cases. Analyzing the incidence and distribution of any disease also helps to provide clues to those at risk based on demographics despite not having any knowledge of the known risk factors. The study of this incidence of a disease is known as epidemiology.
Most cases of Parkinson’s disease are seen in the elderly mostly in the middle too late years of life. The manifestation of the disease In young adults is a rare occurrence. In the United States about 1 out of every 100 people over the age of 60 years has Parkinson’s disease. This incidence varies across the globe and even among certain communities as discussed below. The number of people living with Parkinson’s disease has increased over the years but this may not be necessarily due to a rise in the percentage of people developing PD.
Instead this has to do with a longer life expectancy. Modern medicine, better living conditions and accessibility to health care services means that the “older live longer”. Naturally the number of people living with Parkinson’s disease has increased accordingly. This is further reflected in the difference of prevalence where there is now about 1 million more people living with Parkinson’s disease in the United States compared to 2005 when there was only about 500,000 Americans with PD. It would also not be untrue to say that Parkinson’s patients have a pre existing neural damage due to genetic or environmental factors and it only worsens with the advancement of age.
Parkinson’s disease affects both men and women. It is, however, more common in men and in some countries like in the United States this may be as much as 1.5 times. This could correlate with certain risk factors like exposure to pesticides and industrial pollutants which may be associated with more male-dominated jobs. However, with more women entering the workplace and having a similar exposure, not to mention the non-occupational exposure, it seems that men are at greater risk for unknown reasons. In addition it is also hypothesized that estrogen may have a neuroprotective effect. Declining oestrogen levels in postmenopausal women and also females using hormone replacement therapy are at a greater risk of development of the disease.
Nationality and Ethnicity
The incidence of Parkinson’s disease varies across the globe. However, this distribution may not be as simple as a geographical or ethnic factor. It is known that the Parkinson’s disease is more prevalent in North America and Europe than in Asia and West Africa. However, certain findings like that of the Parsi community in India indicates that this may not just be a geographical difference. The Parsi community in Mumbai has the world’s highest incidences of Parkinson’s disease where it affects about 328 out of every 100,000 people despite living in a country, India, with one of the world’s lowest incidence of PD (70 out of 100,000).
Family History and Genetics
Despite the focus on a family history and genetics, it is believed this accounts for less than 5% of cases. Having one or more related with the disease increases the susceptibility towards its inheritance. More genes are being identified in familial PD, like the recent VPS35 genetic mutation, but its role is sometimes overstated and hyped in the media. There is no evidence of any genetic mutation or strong family history in the majority of Parkinson’s disease patient although family history is an accepted risk factor. This is further supported by the fact that the incidence in monozygotic and dizygotic twins is about the same. Had genetics been a major factor, the incidence would have been higher in the monozygotic twins.
So far five genes have been identified which are associated with the development of the disease. The gene SNCA (Alpha synuclein) plays a crucial role in the development of disease. It has been proved in scientific studies that individuals who have a higher activity of this gene have a 1.5% chance of developing PD. The remaining associated genes are:
- PARK 2 ( Parkinson’s disease autosomal recessive juvenile 2)
- PARK 7 ( Parkinson’s disease autosomal recessive, early onset 7)
- PINK 1 (PTEN – induced putative kinase 1)
- LRRK2 (leucine rich repeat kinase 2)
Individuals exposed to agricultural toxins such as herbicides and pesticides are at a comparatively greater risk of the development of Parkinson’s disease as a few of these toxins inhibit the dopamine production and aggravate the damage caused by free radicals. Farmers, thus have a higher prevalence of PD. Other toxins might include manganese, carbon monoxide, and carbon disulphide.
Traumatic brain injury is associated with an increased risk of subsequent development of Parkinson’s disease. A very famous example is of the Young boxer Muhammad Ali having a diagnosis of young onset Parkinson’s disease following a career in boxing which involves frequent and severe head injuries. The injury is known to cause direct or indirect damage to the dopamine producing nerve cells thereby leading to PD. The mechanism involved could be a provoked inflammatory process, Due to the tiny bleeds deep in the brain that might eventually scar in the substantia nigra region of the brain, which contains majority of the dopamine producing nerve cells.
Based on these factors, one could surmise that the person who is at greatest risk would be :
Over the age of 60
Living in North America
From a family with a strong history of PD
Exposed to agricultural toxins
Have had a head trauma
However, with Parkinson’s disease the incidence and risk factors are not as conclusive as one would think. Some individuals might have one or more of the above risk factors and never experience any symptoms. It is thus safe to say that in the backdrop of the unidentified causes in the majority of PD cases, the epidemiology has not provided definitive risk factors apart from age.