The available evidence indicates that men have a slightly higher risk of parkinson-ism than women, with the exception of drug-induced parkinsonism (59,60). According to a meta-analysis, relative risk of parkinsonism for men compared to women is 1.5% (61). Suggested reasons for this risk included differential exposure to external risk factors, an X-linked genetic factor, and mitochondrial dysfunction. The lifetime risk of parkinsonism is greater in men than in women (4.4% vs. 3.7%) (32). In older patients, 65 to 84 years, the male to female incidence ratio was 1.66 for parkinsonism and 2.13 for PD (19). Interestingly, although women have a longer life expectancy than men, women with PD have the same mortality rates as men with PD (60).
GEOGRAPHY, ETHNICITY, RACE, AND PARKINSONISM
Parkinsonism has been reported in all countries and in all races. In most countries, geography, ethnicity, and race are intertwined. Comparing immigrants to residents of their homeland is one way to evaluate the associations with the risk of parkinsonism.
The only reported large geographic cluster of well-documented parkinsonism is the Parkinson-dementia-amyotrophic lateral sclerosis (ALS) complex of Guam, and this may be related to consumption of Cycad sp. seeds (62).
Although several studies have suggested that those with darker skin have a reduced risk of PD compared to lighter skin individuals (25,63), a review of 20 studies of PD in African-Americans found no consistent evidence to support this theory (64). The authors believed that ascertainment bias compromised the studies they reviewed. Studies that included communities with a mixed population did not observe any racial differences (55,65). Two studies conducted by the same investigator using similar methodology showed that the prevalence rate in African-Americans was five times higher than in the Nigerians who presumably share a common genetic background (55,66). This difference remained significant when the life expectancy in the general population in the two countries was taken into account.
There is no evidence that darker-skinned persons have larger numbers of sub-stantia nigra-pigmented neurons nor is the vulnerability of these neurons different in different races. In one dopa-responsive dystonia autopsied case, we discovered markedly hypopigmented substantia nigra, but the skin color and tendency to tan were similar to her other siblings (67). Thus, skin color by itself does not appear to be related to the risk of parkinsonism or PD.
Arural population in Taiwan (Republic of China) had prevalence rates similar to Western studies but greater than that in mainland China (People's Republic of China), which is an evidence of environment playing a greater role than race (27). Chinese, Malays, and East Indians in Singapore had equal PD prevalence of approximately 300/105 (68). A California study (69) did find differences in incidence rates associated with race with Hispanics having the highest rate followed by non-Hispanic whites, Asians, and blacks.
Incidence and prevalence rates do vary between and within countries. The lowest reported PD prevalence rate is 57/105 population in China (People's Republic of China) (52), followed by 65.6/105 in Sardinia (25), 67/105 in Nigeria (66), 80.6/105 in Japan (70), and the highest reported rate of 775/105 in Australia (51).
Geographic differences between different Western Canadian provinces have been reported (71), and a north-south gradient in the United States has been suggested in one study (72), but not confirmed by others (73). Difference in incidence of parkinsonism based on the population density in Saskatchewan revealed that those born and raised in smaller communities (with population 200 or less) had an increased risk of early onset parkinsonism (74). Several other North American and European reports (75-78) noted higher risk of PD with rural residence during early age, but others (79,80) failed to substantiate this finding. One Canadian study (81) noted no increase in the risk of PD in those who had previously lived in the rural areas or had worked on the farm.
In summary, geographic differences for PD risk are attributable to shared geography, which points to a shared environmental exposure and are not linked to skin color or ethnic background.
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