Previous articles have looked at Parkinson’s disease early symptoms, the 4 Cardinal Signs, Associated Symptoms and Neuropsychiatric Dysfunction. Following the articles ‘What is Parkinson’s disease and Parkinsonism‘ and Parkinson’s disease statistics, we will now cover Parkinson’s disease causes, including Parkinson’s disease risk factors.
Parkinson’s Disease Causes
The condition now known as Parkinson’s disease has been documented in some form for millenia. Notable early recorded examples include those from approximately 500 BC in China (Nei Jun) and 5000 BC in India (Ayurveda). In fact, seeds that contain L-Dopa have been used in India for over 6000 years to treat Parkinson’s symptoms. Despite this rich tradition, the precise mechanism to account for Parkinson’s disease (in particular, to account for dopamine cell death) is still not completely known. As such, there is currently no known definite factor or biological marker associated with Parkinson’s disease causes.
Parkinson’s Disease Risk Factors
Various studies indicate that there appears to be a number of factors linked to the risk of developing Parkinson’s disease. However, it must be noted that the risk figures quoted do vary (sometimes significantly) depending on one’s source. Factors include:
Genetic/Genetic Mutation
- It would appear that if a close relative has/had the disease, the total increased risk of developing Parkinson’s is between 2% – 5% and possibly up to 15%.
- Genes appearing to be involved included Alpha-Synuclein and Parkin, with others such as PINK1, LRRK2 and DJ-1 also possibly playing a role.
- Those with known gene mutation tend to develop the disease under 50 years of age i.e. epidemiological evidence suggests gene mutation plays a more significant role in Young Onset Parkinson’s disease.
- Juvenile Parkinson’s occurs below the age of 20 and runs in families. It is often linked to the Parkin gene and is most common in Japan.
- Red haired people have up to 2x risk of developing Parkinson’s.
Age
- Parkinson’s usually develops mid to late life and the risk increases with age.
- The average age of diagnosis is 60 years.
- Only 5% of Parkinson’s patients are below 40 years of age.
- Interestingly, Parkinson’s disease is virtually unknown in extremely old people 110+ years of age.
Gender
Figures vary considerably between sources and these range from:
- No difference between male and females.
- Males are up to 50% more at risk than females.
- Some sources note a ratio of male (3): female (2), whereas others report that both sexes are affected equally over 75 years of age.
- Men appear to be at double the risk of developing Parkinson’s Disease than women. Support for this comes from 2 sources of data; women who have had hysterectomies have a somewhat higher rate of developing Parkinson’s disease, and those who have had estrogen replacement therapy have a lower rate of Parkinson’s disease when compared to other women their age. The assumption is that estrogens may play a function in protecting the body from the chemical changes that occur in Parkinson’s disease.
- Interestingly, more females are reported as having Parkinson’s in Japan than males.
Race
Figures vary between sources and these range from:
- No difference between race groups.
- Where variations are noted, there appears no difference between race groups from similar locations.
- Some sources note that Parkinson’s is more prevalent in Caucasians with figures up to 187 people per 100,000.
- Individuals of European descent appear most prone to typical Parkinson’s Disease, whereas non-Caucasians may be more at risk for a particular type of non-typical Parkinson associated with disturbance in judgment.
- A UK study suggested that there may be race group differences with regard to the symptoms displayed e.g. poorer performance of Levodopa in Indian and Afro-Caribbean patients.
Environment
A variety of potential environmental factors have been proposed and epidemiological evidence suggest that they play a more significant role in patients over 50 years of age. Examples include:
Toxins
The potential significance of this factor can be demonstrated by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). This chemical can be produced accidentally when trying to illegally manufacture the recreational opioid analgesic drug called MPPP. MPTP has provided a useful Parkinson’s disease model because its neurotoxin properties cause a permanent form of Parkinsonism as a result of it destroying the substantia nigra’s dopaminergic neurons.
Herbicides, Pesticides and Insecticides
- Statistics show that there is a higher rate of Parkinson’s in developed countries, especially in those areas of rural location. Although detection and reporting rates would be expected to be higher in developed countries than compared to less developed ones, the rural aspect may suggest increased exposure to pesticides etc. from farming practices.
- The highest percentage of people in the world with Parkinson’s are found in Nebraska with 329.3 people per 100,000. Agricultural practices using pesticides e.g. Rotenone, and insecticide are suspected contributory factors.
- One particular study in BMC Neurology noted that the increase in risk from exposure to pesticides was:
- 1.6x in general
- 2x when exposed 200 days a year.
- 2.15x for men who used them regularly.
- 2.43x for women who used them regularly.
- In addition, exposure to home/garden insecticides and herbicides appears to carry a greater risk than occupational use.
Bacteria and Viruses
Support for this aspect comes from a both old and new evidence. For example:
- Dale and Church (2004) paper described the link between modern cases of a disease caused by the bacteria Encephalitis Lethargica and a post World War 1 illness that swept the world. They noted similarites of symptoms including sleep disorders, lethargy, parkinsonism, dyskinesias and neuropsychiatric issues. The original illness was a devastating brain attacking condition affecting over 5 million people that left its victims like living statues without the ability to move or speak. The 1917-1928 outbreak was portrayed in the Robert De Niro/Robin Williams film ‘Awakenings’ and was based on the work of British neurologist Oliver Sacks. In 1969, he used the newly developed drug L-Dopa to treat and awaken patients who had remained in a catatonic state dating back from the 1920’s outbreak.
- Many post 1918 Spanish flu (Avian H1N1) patients with encephalopathy went on to develop Parkinson-like symptoms.
- Japanese B encephalitis can produce Parkinson-like symptoms.
- A recent study in Nature Neuroscience suggests that,”infection or other factors that cause certain types of brain inflammation and high levels of Interferon Gamma can predispose one to Parkinsonism or even cause it outright.”
- Another recent study presented to the American Society for Microbiology suggested a possible link with the bacterial infection Helicobacter Pylori (responsible for stomach ulcers) and Parkinson’s disease.
Other possible Parkinson’s disease risk factors proposed include:
- Mitochondria causing oxidative stress due to creating free radicals.
- Excessive build up of proteins in cells because failure in Cell Protein Disposal.
- Previous head injury.
- Severe trauma or stress.
In addition, it has been suggested that there is a greater risk of developing Parkinson’s with:
- People who have obsessive personalities, or
- People who exhibit an impaired sense of smell.
Surprising statistics concerning Parkinson’s disease risk factors:
- Caffeine appears to reduce the risk of developing Parkinson’s disease. For example, a study of Japanese-American men suggested the risk of developing Parkinson’s was less in those who drank coffee regularly and decreased proportionally to the amount consumed.
- Smokers risk may be reduced down to a third compared to non-smokers. Why? Most likely because Nicotine may act as a dopamine stimulant and smoke contains MAO inhibitors which help prevent dopamine breakdown.
- People with high cholesterol are less likely to get Parkinson’s.
Having looked into Parkinson’s disease causes and Parkinson’s disease risk factors, the next article in the series will address Parkinson’s disease diagnosis.