PD is an illness that usually affects the elderly. It is a degenerative disease of the brain in which loss of cells in the basal ganglia results in progressively increasing physical disability.
The function of the basal ganglia in healthy people
The basal ganglia consist of various components (Fig. 1), the most important being the substantia nigra (SN), subthalamic nucleus (STN) and globus pallidus interna (GPi). These components send electrical signals to each other via a chemical messenger, dopamine. The “communication” between these components is vital for the function of the basal ganglia in coordinating movements of the body.
The abnormal function of the basal ganglia in PD
The primary process in PD is the loss of brain cells in the substantia nigra (SN), which results in deficiency of dopamine. As dopamine is important for the normal function of the basal ganglia, this disturbance of motor circuits leads to loss of control of the normal activity of components of basal ganglia, resulting in hyperactivity (excessive activity) of the STN and GPi. The actual processes in the basal ganglia are complicated; suffice to state that hyperactivity of STN and GPi causes the symptoms of PD such as tremor, stiffness and slowness of movement (Albin RL, Young AB and Penney JB, 1989; DeLong MR, 1990).
What causes the loss of brain cells in the SN?
The actual cause of the loss of brain cells at the SN is still a mystery. It is suspected to be the result of the interplay between environmental and genetic factors. According to the “double-hit hypothesis” (Fig. 2), PD occurs in patients who have genetic susceptibility that has rendered their brain vulnerable to the damaging effect of environmental factors. The relative contribution of these two factors varies from one country to another.
The environmental factors have not been identified with certainty. Exposure to pesticides and herbicides, drug abuse and handling of heavy metals have been reported (please refer to following section).
What are the risk factors for PD?
Many risk factors have been identified (Tanner CM, 1992) such as the following:
Among all the risk factors for PD, the age factor is the strongest as it has been consistently documented in every study. The risk of developing PD increases proportionately with age.
Although some studies have shown gender differences in PD, overall there is no obvious difference in risk between men and women.
Community-based studies have shown that the percentage of people with PD is higher in Europe and North America (150 per 100 000 population) than in Asia (50 per 100 000 population). The reason for this observation is unknown. It could be due to genetic or environmental factors peculiar to these countries.
d) Genetic predisposition
Studies in other countries have shown that the percentage of patients with family history is in the region of 6-24% (Brique S, 1997). I have seen several families of PD but they are rare. In Malaysia, the percentage of familial PD has been reported to be just 2% despite a large average family size of 5.5 (Chew NK, Goh KJ and Tan CT, 1998). Thus, genetic factor does not seem to play an important role in the causation of PD in Malaysia.
Over the past five years, a number of genes have been found in the inherited forms of PD. The first to be identified was a mutation (alteration in gene sequence) in the alpha-synuclein gene that caused relatively young-onset PD in Italian and Greek families (Polymeropoulos MH et al, 1997). The symptoms started at the age of 40 to 50 years, with an average of 40 years. Another mutation which affects the parkin gene was found in Japanese families with symptoms of PD starting in their 20′s (Kitada T et al, 1998). Subsequently, more gene mutations were identified and termed PARK3 right up to PARK8. So far, there has been no genetic study of PD in Malaysia.
e) Exposure to toxic substances
The possible role of toxic substances in the environment was suggested by the observation that farmers and people living in rural areas (that may have been exposed to pesticides) have a slightly higher risk of developing PD. Other studies have shown that people who were exposed to heavy metals (lead, manganese, mercury) in certain industrial areas were predisposed to developing PD.
In 1983, a peculiar parkinsonian syndrome appeared in drug addicts in California, following exposure to a “heroine-like” drug substance, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This inadvertent human experiment provided a hint that other chemical substances similar to MPTP might cause PD.
What are the protective factors for PD?
It has been reported that regular intake of vitamin E was associated with lower risk of getting PD (Tanner CM et al, 1988). Interestingly, regular coffee drinking (Benedetti MD et al, 2000) and black tea (Tan LC et al, 2007) appears to confer protection against the development of PD (Benedetti MD et al, 2000). In animal studies, caffeine, the chemical agent that is present in coffee, has been shown to have a protective effect on the brain cells (Chen JF et al, 2001). On the other hand, cCigarette smoking has also been associated with reduced risk of developing PD (Baumann RJ et al, 1980). Nevertheless, it has to be stated that the dangers of smoking far outweigh any beneficial effect it might have on PD.
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