Our study was performed using recent population-based data encompassing the entire population of Korea. This is currently the only nationwide epidemiological study of PD in Korea. Furthermore, to the best of our knowledge, this is the first nationwide study that employed data from an entire population using uniform diagnostic criteria to assess recent temporal trends in the incidence and prevalence of PD in Asia.
Our results indicate an increasing trend in the annual prevalence and incidence rates of PD over the past 6 years. In our study, there were 16,152 new PD cases from 2010 to 2015, with a mean annual incidence of 23.9 cases per 100,000 individuals. The incidence of PD in men steadily increased throughout the study period. Conversely, the trend remained stable in women until 2013, then an increase in the incidence of PD was observed from 2014 onwards. The number of actual incident cases also gradually increased in both men and women. The lack of a clear trend in the incidence rate across the genders may be due to a difference in the denominator population caused by the growing aging population, especially among women.
Similar to our findings, several previous studies also reported an increase in the incidence of PD over time. In a 30-year study conducted in Olmsted County, Minnesota, Savica et al.  reported that the incidence of PD increased in men and remained stable in women. Only a few other studies evaluating trends in the incidence of PD have been conducted in the United Kingdom [13, 17], United States [9, 11], Netherlands , France , and Taiwan [10, 14]. These studies reported either a stable incidence [11, 16], a slight decrease [12,13,14, 17], or an increase [9, 10] in the incidence of PD over time. However, most of these studies [10, 11, 13, 14, 16] identified patients with PD through algorithmic searches of administrative databases without using reliable uniform diagnostic criteria. There is a substantial potential for misclassification when using this approach, making the results of these studies difficult to interpret.
The first possible cause for an increase in the incidence rate of PD is an increasingly older population. As PD is a neurodegenerative disease, increased incidence is expected in an ageing population . The second possible explanation is an increased awareness of PD in patients and physicians as well as the availability of co-payments through the RID program. This leads to the diagnosis of previously undiagnosed cases and swifter referrals of patients with PD. In other words, there is a growing willingness to consult doctors regarding symptoms that were previously considered a normal part of aging which increases the likelihood that patients are examined by a neurologist. However, given the different trends observed in men and women and our consistent patient identification strategy, the observed increase is likely to be a real increase in incidence and prevalence.
We observed a gradual increase in the prevalence of PD throughout the study period. Similar results have also been reported in studies conducted in Japan , Taiwan [10, 14], and France  in the past decade. Both changes in the incidence of PD over time and the survival time of individuals with PD affect the prevalence of PD .
Interestingly, the present study demonstrated a preponderance in the prevalence and incidence of PD in the female population. Previous studies conducted on Western populations seem to indicate that PD is predominant in males [9, 13, 17, 18]. However, many Asian studies have reported female preponderance in PD [22, 24,25,26,27,28], while only some studies showed only male preponderance , or no difference between the genders [10, 29]. The reasons for this discrepancy are unclear and may be the results of several compounding factors. First, Asian individuals have different genetic susceptibilities and experience different environmental factors. Second, Asian women may face more risk factors, such as pesticide use, head trauma, agricultural occupations, toxic exposure, dietary deficiencies, and well-water drinking. Alternatively Asian women may also have fewer preventing factors, such as smoking, coffee drinking, and alcohol consumption compared to Western women . Third, the ageing female population is increasing more rapidly than the male population . Finally, men are more likely to be underdiagnosed because they have more competing diseases than women.
The incidence and prevalence of PD were higher in women than in men in patients over the age of 50, and higher in men than in women in patients with young onset PD. The neuroprotective effect of estrogen  is speculated to be the reason for the higher incident rate in male patients with young onset PD. However, the protective effects of estrogen decrease after menopause likely causing the observed increase in the incidence and prevalence of PD in the aging post-menopausal female population.
PD rarely developed before 50 years old, and the incidence increased sharply in patients in their 60s. The number of PD cases was highest in both male and female patients in their 70s during the entire study period. In the male population, the prevalence and incidence of PD consistently peaked between 80 and 89 years. In the female population, the peak prevalence and incidence of PD was between 70 and 79 years in 2010 and then increased to 80 and 89 years between 2012 and 2014. Any positive changes made in environmental risk factors in women seem to delay the onset of PD.
From 2010 to 2015, the prevalence of PD increased in all regions of the country. The incidence of PD also increased in all regions except for Sejong-si (a new administrative metropolitan city separated in 2012). In 2015, the highest incidence and prevalence of PD was in Jeonbuk province. These findings can be utilized by policy makers to prioritize advancements in national health.
This study has certain strengths. First, this is a nationwide study that surveyed the entire population of Korea for 6 years. This nationwide evaluation of the epidemiological features of PD provides a better understanding of the national patterns of PD epidemiology in South Korean patients with a recent diagnosis of PD. This study had no selection bias as it examined a stable and generalized population. Second, the epidemiological data in this study is more reliable than the data reported in previous studies because clear and uniform diagnostic criteria were used. Most previous nationwide studies used algorithmic searches of administrative databases to diagnose PD patients leading to potential misclassification depending on the different algorithms used. To the best of our knowledge, this study is the first Asian study to examine long-term trends in the incidence of PD using uniform and reliable diagnostic criteria.
This study also has a few limitations. First, because we used insurance claims data, we could not rule out the possibility of the misclassification of patients with PD. However, the diagnosis of PD in the RID database is based on diagnostic criteria standardized in hospitals by the NHI. Before being submitted to the NHI, the physician’s diagnosis passes through a verification process and is reviewed by another health care personnel in their institution. Through this process, we are certain that a diagnosis in the RID database has a relatively higher accuracy than other insurance data. This is also confirmed by other epidemiological studies of RID, in which a high agreement has been reported between hospital and administration data [31, 32]. Although neuropathological assessment is the gold standard for diagnosis of PD, there are no generally accepted standard pathological diagnostic criteria for PD , and the diagnosis of PD relies on clinical examination [3, 34]. Second, we could not identify the stage of PD in this study. Third, the diagnosis of PD is likely to be underestimated because of low hospital utilization or other comorbid diseases in older patients . There may be an unknown number of individuals with PD who were not accurately diagnosed because of inadequate facilities and staffing in areas of low socioeconomic status. Although other studies have used several methods to calculate the number of patients with PD in a community, there is no gold standard and each method has its own limitations [35, 36]. Fourth, we could not identify risk factors because we were unable to access the underlying disease information of PD patients. Therefore, we were unable to directly examine whether changes in environmental risk factors, such as a decreased prevalence of smoking, were responsible for the observed increase in the incidence of PD. Finally, the number of prevalent cases in that year excluded not only the number of patients who died, but also the number of people who have become disqualified (prison, military, immigration, etc.) in the previous year. Currently, the NHIS-RID database does not provide information on insurance disqualification. Hence, the observed prevalence may be affected by the number of deaths and the number of people disqualified each year. However, the difference caused by this discrepancy will not be large. The results of this study will contribute greatly to further research by presenting precise macroscopic epidemiologic data.