The global, regional, and National burden of parkinson’s disease in 204 countries and territories, 1990–2021: a systematic analysis for the global burden of disease study 2021

Abstract

Background

Parkinson’s disease (PD) represents a prevalent neurodegenerative condition that leads to significant disability and contributes to a growing public health challenge worldwide. However, a comprehensive report on progress from 1990 to 2021 is still lacking, especially regarding the risk factors associated with PD by gender and age. This study aims to examine the patterns of PD incidence, mortality rates, and disability-adjusted life years (DALYs) across all age groups, along with the risk factors linked to PD-related fatalities, spanning the years from 1990 to 2021.

Methods

We retrieved data on PD from the Global Burden of Disease Study 2021. The burden of PD was assessed using incidence, deaths, and DALYs, with corresponding 95% uncertainty interval (UI). Analyses were conducted globally, regionally, and nationally for the period between 1990 and 2021, stratified by age, sex, and the Socio-demographic Index (SDI). Estimated annual percentage changes (EAPCs) were calculated to assess temporal trends. Only cases directly attributable to PD were included, and a comorbidity correction was applied to ensure accurate estimation of the burden.

Results

In 2021, there were 13.35 million (95% UI: 12.67–14.08) incident cases and 388,194 (95% UI: 347,250–417,388) deaths cases globally. The global DALYs attributed to PD climbed from 53.51 to 94.68 per 100,000 population (95% UI: 49.54–57.56 to 85.37–103.11) from 1990 to 2021. During the same period, age-standardized incidence rates rose from 7.82 to 16.92 per 100,000 population (95% UI: 6.95–8.75 to 15.16–18.82), while mortality rates increased from 2.78 to 4.91 per 100,000 population (95% UI: 2.55–2.97 to 4.40–5.29). Among the five SDI regions, the high SDI region reported the highest PD mortality rate in 2021. The burden of PD was most pronounced in the 85–89 age group. Smoking was identified as a key risk factor for PD-associated mortality in 2021, with the proportion of deaths attributable to smoking ranging from − 9.09% in individuals aged 50–54 years to -2.69% in those aged 95 years and older.

Conclusions

PD represents a significant and escalating global health challenge, driven by increasing incidence rates and an aging population. This growing burden highlights the urgent need for effective strategies in prevention, early diagnosis, and tailored management, particularly for elderly males who are disproportionately affected. Addressing modifiable risk factors and advancing etiological research are crucial to mitigating the rising prevalence and optimizing resource allocation. Coordinated public health interventions and robust healthcare policies are essential to reduce the global impact of PD and improve outcomes for affected individuals.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12889-025-23492-8.

Background

Parkinson’s disease (PD) is a common neurodegenerative disorder that causes major disability and an increasing global public health burden related to motor, non-motor, and cognitive features [1]. The primary motor symptoms of PD include resting tremor, bradykinesia, rigidity, and postural instability [2]. Additionally, PD patients often experience non-motor symptoms such as hyposmia, constipation, urinary dysfunction, and sleep disorders [3]. As the illness advances, these indications become more severe, significantly affecting the quality of life and daily activities of patients. With increased survival into elderly age, the absolute number of people living with PD has risen and is projected to continue rising, leading some to describe it as a global pandemic [4]. A systematic analysis of data from the Global Burden of Disease (GBD) Study 2016 estimated that crude prevalence of PD increased by 74% between 1990 and 2016, but that the increase in age-standardized prevalence was only 22% when demographics were taken into account [5]. The GBD Study 2019 estimated that more than 8.5 million people worldwide suffer from PD [6]. The GBD study conducted in 2021 revised these figures to indicate increasing to 11.76 million by 2021 for PD, attributed to roughly 7.47 million disability-adjusted life years (DALYs) and resulting in 388,000 fatalities [7, 8]. As life expectancy increases, the number of individuals affected by PD is expected to rise, resulting in a greater prevalence of advanced stages of the condition [9, 10].

Following Alzheimer’s disease, PD stands as the second most common neurodegenerative disorder [11]. PD is characterized by two major pathological changes: the progressive loss of dopaminergic neurons in the central substantia nigra and the presence of Lewy bodies in the remaining neurons [12]. Nevertheless, the etiology of PD remains unclear, and studies have suggested that its onset may be related to aging, genetics, and environmental factors [13]. In addition, the course of PD is irreversible, and the corresponding pathological changes occur long before the onset of clinical symptoms [14]. Therefore, identifying the risk factors associated with PD and intervening appropriately in the potential therapeutic time window prior to the onset of clinical symptoms can help to prevent and delay disease progression. The risk of developing the disease is significantly increased by several factors, including exposure to pesticides or herbicides, high dairy intake, a history of melanoma, and traumatic brain injury [15–18]. Besides focusing on high-risk factors, it is even more important to research protective factors, as they form the foundation for early intervention and help slow disease progression. Previous studies have revealed that a reduced risk of morbidity is linked to smoking, caffeine intake, higher blood uric acid levels, regular exercise, and the use of medications like ibuprofen [13, 19–22]. However, a counterargument suggests that the rewarding effects of nicotine may diminish in patients at the prodromal stage of PD [23]. This reduction may lead these individuals to stop smoking, resulting in a negative correlation between smoking and morbidity. However, this hypothesis fails to account for the reduced prevalence in individuals who have previously smoked in comparison to those who have never smoked. whether this association is causal remains unclear, indicating that further research is necessary. PD is anticipated to emerge as a significant public health issue, consequently exacerbating the economic strain on society in the future. Hence, the projected increase in population life expectancy in the following decades will presumably bring about additional health, social and economic challenges due to PD globally, highlighting the need for further improvements in preventive and treatment strategies [24, 25].

Accurate evaluation of the existing burden and associated risk factors for PD is essential, as it plays a vital role in the formulation of effective control and prevention measures. An earlier research project studied the effects of PD from 1990 to 2016, based on findings from the GBD 2016 report.⁵ Nonetheless, considering the progress in research and the availability of new information, it is essential to conduct a re-evaluation. Importantly, following the update of the Global Burden of Disease, incidence, DALYs, and Risk Factor Study in 2021 (GBD 2021), there has been a lack of a systematic study that comprehensively updates the epidemiological trends in PD. Moreover, earlier research has focused on the epidemiological characteristics of PD during designated time frames within specific nations or areas [26–28]. There is currently insufficient research using the updated GBD database to explore trends in PD over nearly three decades, from 1990 to 2021, and to assess the epidemiological context of PD in 2021. Our study is conducted on a larger scale and covers an extended period, incorporating the latest data. Consequently, utilizing the GBD 2021 data, this research intends to conduct a comprehensive and methodical examination of the disease burden associated with PD. In particular, this study aims to assess the global, regional, and national patterns in the incidence of PD, mortality rates, DALYs, and associated risk factors. This evaluation is of great importance, as it provides essential epidemiological data that can inform policymaking and intervention strategies.

Materials and methods

Data collection

This cross-sectional study was approved by the First Affiliated Hospital of Anhui Medical University. The ethical board of the First Affiliated Hospital of Anhui Medical University granted a waiver of informed consent as the study only involved data analysis and no identifiable personal information. Available data, standardized disease definitions and prevalence information were collected for PD at all ages using the Global Health Data Exchange query tool created by GBD collaborators [7].

GBD 2021 uses a standardized, comparable approach to comprehensively investigate the incidence, prevalence, and DALYs of 371 diseases and injuries across 204 countries/territories worldwide, to understand the health losses caused by various ailments [7]. All analysis codes used in the GBD 2021 study are publicly available online (http://www.ghdx.healthdata.org). This analysis adheres to the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) statement [29]. In this study, we collected data regarding the number of cases and incidence of PD, mortality, and PD-associated DALYs, along with their corresponding rates at global, regional, and national levels. Data on the race and ethnicity of the participants are not listed in the GBD database, which does not allocate race and ethnicity for data collection. We computed mean estimated annual percentage changes (EAPCs) using linear regression. We also collected data regarding global risk factors that contribute to PD mortality and DALYs in all-age. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines.

Definitions

The International Classification of Diseases tenth revision (ICD-10) codes for PD are G20, G21, and G22. According to GBD 2021, PD is defined by the presence of at least two of the following four primary symptoms: tremors or trembling, bradykinesia, stiffness of limbs and torso, and postural instability.

Sociodemographic index

Sociodemographic Index (SDI) is a measure of a countries or region’s level of development based on data on fertility rate, education level, and per capita income. SDI ranges from 0 to 1; higher levels indicate greater socioeconomic development. The SDI is reportedly associated with disease incidences and mortality rates. In this study, countries and geographic regions were classified into 5 SDI regions (low, low middle, middle, high-middle, and high) to explore the association between the burden of PD and socioeconomic development.

Data analysis

Incidence, mortality, DALYs, and their corresponding rates served as the primary indicators for quantifying the burden of PD. Each rate is reported per 100,000 population, along with 95% uncertainty interval (UI) according to the GBD algorithm [30]. The dynamics of PD were analyzed by calculating EAPCs to identify temporal trends in the disease burden [31]; 95% confidence intervals (CIs) of EAPCs were determined by linear modeling [32]. If the upper limit of both EAPC and its 95% CI is negative, its corresponding rate shows a decreasing trend; conversely, if the lower limit of both EAPC and its 95% CI is positive, its corresponding rate shows an increasing trend. Gaussian curves were used to analyze associations between EAPC and rates and the Human Development Index (HDI) of PD in all-age. Additionally, risk factors for PD in all-age were assessed. All statistical analyses were conducted using R version 4.2.0, and data visualizations were created with Adobe Illustrator 2020. All P values were 2-sided, and p < 0.05 was considered statistically significant.

Results

PD in All-Age: global trends

Incidence

A total of 11,767,271(6,438,639 male [54.72%]; 5,328,632 female [45.28%]) were included in the analysis. In 2021, the global incident cases of PD in All-age were 1,335,142 (95% uncertainty interval [UI],1,196,373-1,485,216). From 1990 to 2021, the global incident cases of PD increased by 220% (95% UI, 210-229%). The corresponding incidence rate increased accordingly 7.821 (95%UI, 6.949–8.753) in 1990 to 16.919 (95% UI, 15.161–18.821) in 2021. From 1990 to 2021, the EAPC was 2.56 (95% CI, 2.50–2.61), indicating a global increasing trend in both the number of PD and the all-ages incidence of PD (Fig. 1A and Table 1). The gender differences in the incidence of PD are significant, with the rate for males more than 1.3 times that of females. The PD incidence rate was 19.25 per 100,000 (95% UI, 17.26–21.49) for males, compared to 14.57 per 100,000 (95% UI 13.09–16.22) for females. In absolute numbers, the total number of PD incidence was 762,142 (95% UI, 683,407–850,674) in men compared with 573,000 (95% UI, 514,626–637,747; Fig. 2A) in women. PD incidence and burden showed substantial variation by age group. The 70–74 age group had the highest number of incidences at 236,234 (95% UI, 187,603 − 284,527). The 85–89 age group had the highest incidence rate at 417.62 per 100,000 (95% UI, 296.68-571.56). The under-70 age group experienced the largest increase in incidence rate, rising from 3.52 per 100,000 (95% UI, 2.96–4.21) in 1990 to 7.67 per 100,000 (95% UI, 6.48–9.24) in 2021. Across all age groups, males had higher incidence rate compared to females (Fig. 2A).

Fig. 1.

Epidemiologic Trends of Incidence, Death, and Disability-Adjusted Life-Years (DALYs) Rates in 5 Sociodemographic Index (SDI) Regions of all-ages PD From 1990 to 2021. (A) Trends in incidence rate; (B) Trends in death rate; (C) Trends in DALYs rate

Table 1.

Incidence of parkinson’s disease between 1990 and 2021 at the global and regional level

Location	Rate per 100,000 (95%UI)
	1990		2021		1990–2021
	Incident cases	Incidence rate	Incident cases	Incidence rate	Cases change	EAPCa
Global	417134.69 (370654.53–466859.89)	7.82 (6.95–8.75)	1335142.12 (1196373.04–1485216.84)	16.92 (15.16–18.82)	2.20 (2.10–2.29)	2.56 (2.50–2.61)
SDI
High-middle SDI	120875.25 (107308.27–135760.59)	11.37 (10.09–12.77)	367914.10 (322893.75–418790.6)	28.21 (24.76–32.12)	2.04 (1.92–2.21)	2.96 (2.91–3.01)
Low-middle SDI	51953.323 (46223.71–58310.04)	4.47 (3.98–5.02)	158405.68 (141540.71–176126.65)	8.25 (7.37–9.17)	2.05 (1.96–2.15)	2.10 (2.01–2.19)
Low SDI	1699.16 (15193.27–18976.11)	3.39 (3.03–3.79)	44822.49 (40182.46–49572.55)	4.01 (3.60–4.44)	1.64 (1.57–1.71)	0.58 (0.46–0.70)
High SDI	130050.41 (117351.75–143567.08)	14.79 (13.34–,16.32)	327961.71 (304409.20–352285.61)	29.98 (27.82–32.20)	1.52 (1.42–1.64)	2.33 (2.31–2.34)
Middle SDI	96793.70 (84662.37–110440.45)	5.62 (4.91–6.41)	435098.08 (379286.32–492734.48)	17.77 (15.49–20.12)	3.50 (3.32–3.69)	3.86 (3.79–3.94)
East Asia	94427.43 (80165.82–109879.36)	7.76 (6.59–9.03)	523098.68 (445049.76–607919.25)	35.52 (30.22–41.28)	4.54 (4.19–4.90)	5.15 (5.09–5.21)
Southeast Asia	20675.05 (18665.23–22838.43)	4.44 (4.01–4.91)	67603.17 (61544.01–74556.25)	9.68 (8.81–10.68)	2.27 (2.16–2.41)	2.54 (2.47–2.61)
Oceania	252.64 (220.86–289.52)	3.857 (3.37–4.42)	691.04 (609.55–770.06)	4.96 (4.38–5.53)	1.74 (1.52–1.96)	0.81 (0.73–0.89)
Central Asia	4445.68 (3977.86–4920.86)	6.414 (5.74–7.10)	8713.71 (7945.62–9479.62)	9.09 (8.29–9.89)	0.96 (0.82–1.11)	1.14 (1.07–1.21)
Western Europe	85896.26 (79497.19–92555.42)	22.35 (20.68–24.08)	175481.71 (162555.89–188776.41)	40.12 (37.17–43.16)	1.04 (0.96–1.13)	1.85 (1.77–1.92)
Australasia	2319.71 (2058.15–2516.23)	11.44 (10.15–12.41)	6709.53 (6131.62–7499.99)	21.67 (19.80–24.22)	1.89 (1.67–2.23)	2.08 (2.04–2.12)
Central Europe	17216.56 (15758.02–18640.95)	13.76 (12.60–14.90)	28542.03 (26431.61–30625.29)	24.76 (22.93–26.57)	0.66 (0.59–0.73)	1.95 (1.90–1.99)
Southern Latin America	5937.17 (5464.23–6375.53)	11.99 (11.03–12.87)	12894.64 (11756.73–14524.91)	19.05 (17.37–21.46)	1.17 (1.02–1.37)	1.58 (1.52–1.63)
Eastern Europe	29598.70 (25435.26–34236.45)	13.07 (11.23–15.12)	39438.48 (34171.90–44856.05)	19.08 (16.53–21.69)	0.33 (0.28–0.39)	1.06 (0.98–1.15)
High-income Asia Pacific	15676.23 (13559.11–18118.68)	9.042 (7.82–10.45)	40940.37 (36458.59–45744.84)	22.08 (19.66–24.67)	1.61 (1.41–1.85)	3.32 (3.18–3.46)
Central Latin America	7063.85 (6442.28–7738.66)	4.30 (3.92–4.71)	29014.82 (26476.74–31819.99)	11.47 (10.46–12.58)	3.11 (2.96–3.26)	3.12 (3.07–3.17)
High-income North America	42383.84 (36182.27–48800.59)	15.06 (12.86–17.34)	102845.30 (95282.59–111010.83)	27.78 (25.74–29.98)	1.43 (1.22–1.30)	1.85 (1.76–1.94)
Caribbean	2062.30 (1908.24–2207.31)	5.84 (5.41–6.25)	5338.45 (4975.38–5724.88)	11.25 (10.48–12.06)	1.59 (1.50–1.69)	2.13 (2.09–2.17)
Andean Latin America	2183.62 (1983.39–2400.56)	5.75 (5.22–6.32)	9787.66 (8728.51–10927.77)	14.80 (13.19–16.52)	3.48 (3.16–3.88)	3.30 (3.23–3.37)
Eastern Sub-Saharan Africa	4967.51 (4422.12–5528.68)	2.60 (2.32–2.90)	12485.79 (11258.78–13758.10)	2.93 (2.64–3.23)	1.51 (1.43–1.59)	0.36 (0.20–0.52)
Tropical Latin America	7661.46 (6555.53–8800.10)	5.02 (4.30–5.77)	27301.26 (23728.02–30990.85)	11.99 (10.43–13.62)	2.56 (2.42–2.73)	2.82 (2.77–2.87)
Central Sub-Saharan Africa	1423.16 (1239.04–1615.87)	2.59 (2.25–2.94)	3860.79 (3408.25–4413.23)	2.82 (2.489–3.223)	1.71 (1.54–1.91)	0.15 (0.01–0.29)
North Africa and Middle East	14690.70 (13242.40–16210.82)	4.33 (3.90–4.78)	54380.13 (48759.63–59977.06)	8.73 (7.83–9.63)	2.70 (2.56–2.85)	2.33 (2.26–2.40)
South Asia	49018.98 (42578.85–56331.58)	4.48 (3.89–5.15)	162627.12 (141805.41–185043.13)	8.81 (7.68–10.02)	2.32 (2.21–2.45)	2.36 (2.24–2.49)
Southern Sub-Saharan Africa	1958.11 (1729.64–2231.78)	3.74 (3.30–4.26)	4871.75 (4250.19–5543.06)	6.07 (5.29–6.90)	1.49 (1.40–1.59)	1.49 (1.41–1.58)
Western Sub-Saharan Africa	7275.737 (6514.09–8125.59)	3.77 (3.37–4.21)	18515.69 (16701.62–20440.50)	3.78 (3.41–4.17)	1.54 (1.45–1.65)	-0.02 (-0.12–0.07)

Abbreviations: EAPC, estimated annual percentage change; SDI, Sociodemographic Index; UI, uncertainty interval. ^aEAPC is expressed as 95% CIs

Fig. 2.

Incidence, death, and DALYs. Rates for PD by age group and sex in 2021. (A) Incidence; (B) Death (C) DALYs

Mortality

Over the past 30 years, the global number of PD-associated deaths increased by 77% (148,068; 95% UI,135,802 − 158,149) in 1990 vs. 388,194 (95%UI, 347,249–417,387) in 2021. Similarly, the PD-associated death rate increased from 2.776 (95%UI, 2.546–2.965) per 100,000 in 1990 to 4.919 (95% UI, 4.400-5.289) per 100,000 in 2021; the EAPC was 1.793 (95% CI, 1.735 to 1.850) (Fig. 1B and eTable 1 in Appendix). The gender differences in the mortality of PD are significant, with the rate for males more than 1.3 times that of females. The PD incidence rate was 5.56 per 100,000 (95% UI, 5.03–6.04) for males, compared to 4.28 per 100,000 (95% UI, 3.64–4.70) for females. In absolute numbers, Deaths from PD among men totaled 219,953 (95% UI, 198,989 − 239,245), while for females it was 168,241 (95% UI, 143,292 − 184,611; Fig. 2B). PD incidence and burden showed substantial variation by age group. The 85–89 age group had the highest number of deaths at 98,150 (95%UI, 84,947 − 109,155). The 85–89 age group had the highest mortality rate at 427.65 per 100,000 (95% UI, 350.74–473.70). The above-20 age group experienced the largest increase in mortality, rising from 4.815 per 100,000 (95% UI, 4.42–5.14) in 1990 to 7.386 per 100,000 (95% UI, 6.61–7.94) in 2021. Across all age groups, males had higher mortality compared to females (Fig. 2B).

DALYs

The global number of PD-associated DALYs in all-age increased by 77% from 1990 to 2021 (2,854,049; 95%UI, 2,642,178-3,069,764) in 1990 vs. 7,471,821 (95% UI, 6,736,685-8,137,067) in 2021; the EAPC was 1.902 (95% CI, 1.88 to 1.92) (Fig. 1C and eTable 2 in Appendix). The gender differences in the DALYs of PD is significant, with the rate for males more than 1.3 times that of females. The rate of PD-associated DALYs among all-age was 107.90 per 100,000 (95%UI, 97.06-118.87) for males, compared to 81.38 per 100,000 (95% UI, 72.26–89.94) for females. In absolute numbers, DALYs from PD among men totaled 4,271,994(95% UI, 3,843,068 − 4,706,572), while for females it was 3,199,826 (95% UI 2,841,371-3,536,422; Fig. 3). The 75–79 age group had the highest number of DALYs at 1,519,123 (95%UI 1,357,588-1,683,047; Fig. C). The 85–89 age group had the highest DALYs rate at 4,262.54 per 100,000 (95% UI, 3,721.44-4,681.33). The under-70 age group experienced the largest increase in DALYs rate, rising from 16.23 per 100,000 (95%UI, 14.56–17.93) in 1990 to 25.65 per 100,000 (95%UI, 22.30-29.14) in 2021. Across all age groups, males had higher DALY rates compared to females (Fig. 2C).

Fig. 3.

Incidence, death, and DALY rates for PD by SDI, from 1990 to 2021 globally and in 21 GBD regions. (A) Incidence; (B) Death (C) DALYs

PD in All-Age: SDI regional trends

Incidence

The Middle SDI region had the most cases of PD in 2021 (435,098; 95% UI, 379,286–492,734). The incident cases in the Low-middle SDI region increased by 350.00% (95% UI, 332.00-369.00%). The greatest increase in the incidence of PD occurred in the Middle SDI region (EAPC, 3.863; 95%CI, 3.790–3.935) (Table 1; Fig. 1A).

Mortality

Among the 5 SDI regions, the High SDI region had the most death cases of PD in 2021 (119,319; 95% UI, 102,312 − 128,104); the Low SDI region had the lowest number of PD-associated deaths in 2021(16,357; 95% UI, 13,718 − 19,476). The death cases in the Middle SDI region increased by 115% (95% UI,91-142%). The mortality of PD was highest in High SDI (10.91; 95% UI, 9.35–11.71). In contrast, the mortality of PD was lowest in Low SDI (1.464; 95% UI, 1.23–1.73). The greatest increase in the mortality of PD occurred in the middle SDI region (EAPC, 2.31; 95%CI, 2.230–2.379). The Low SDI region had the lowest EAPC in the PD-associated mortality rate (0.45; 95%UI, 0.36 to 0.55) (eTable 1 in Appendix and Fig. 1B).

DALYs

In 2021, the Middle SDI region had the highest number of PD-associated DALYs (2217518; 95% UI, 1,971,932-2,467,379) with a dramatic increase of 122% from 1990 to 2021. The high-middle SDI region had the greatest decrease (60.49%) in the number of PD-associated DALYs (eTable 1 in Supplement 1 and Fig. 2C). The rate of PD-associated DALYs was highest in High SDI (184; 95% UI, 165–198). From 1990 to 2021, Middle SDI had the largest increase in the DALYs of PD (EAPC, 2.59; 95%CI, 2.55–2.63), whereas the Low SDI had the smallest increase (EAPC, 0.342;95%CI, 0.19–0.45) (eTable 2 in Appendix and Fig. 1C).

PD in All-Age: geographic regional trends

Incidence

Among 21 geographic regions, East Asia had the most cases of PD in 2021 (523,098; 95% UI, 445,049–607,919), whereas Oceania had the fewest (691;95% UI, 610–770). The incidence of PD was highest in Western Europe (40.12; 95%UI, 37.17–43.16). In contrast, the incidence of PD was lowest in Western Sub-Saharan Africa (3.78; 95% UI, 3.41–4.17). From 1990 to 2021, East Asia had the largest increase in the incidence of PD (EAPC, 5.15;95% CI, 5.09–5.21), whereas the Western Sub-Saharan Africa had the smallest increase (EAPC, -0.02;95% CI, -0.12-0.07) (Table 1). 6 regions (e.g., Western Europe and Central Europe) had higher incidences of PD than the global mean, whereas 15 regions (e.g. e.g., Central Sub-Saharan Africa and Central Europe) had lower incidences than the global mean (16.92) (Fig. 3A).

Mortality

In 2021, High-income North America had the highest number of PD-associated deaths (41,509; 95% UI, 35,667 − 44,444). High-income Asia Pacific had the highest PD-associated mortality rate (12.128;95%UI, 9.89–13.39). Western Sub-Saharan Africa had the highest decrease in the PD-associated mortality rate (EAPC, -0.082; 95%CI, -0.12 to -0.05), whereas High-income Asia Pacific had the largest increase (EAPC, 4.25; 95%CI, 4.13 to 4.38). In 2021, High-income Asia Pacific had the highest PD-associated mortality rate, whereas Central Sub-Saharan Africa had the lowest mortality rate (0.992;95% UI, 0.74–1.25) (eTable 1 in Supplement). As noted previously, the global SDI was 0.66 in 2021; 9 regions had higher PD-associated mortality rates than the global mean, whereas 12 regions had lower rates than the global mean (4.92) (Fig. 3B).

DALYs

In 2021, East Asia had the highest number of PD-associated DALYs (2234333; 95% UI, 1898278–2598616), whereas Oceania had the lowest number (4803; 95% UI, 3902–6101). Western Europe had the highest DALYs rate (221.30; 95% UI, 197.34-240.58); Eastern Sub-Saharan Africa had the lowest DALYs rate (20.67; 95% UI, 16.16–26.25). From 1990 to 2021, Central Sub-Saharan Africa had the highest decrease in the DALYs rate (EAPC, -0.207; 95% CI, -0.347 to -0.066); Tropical Latin America had the largest increase (EAPC, 2.857; 95% CI, 2.80 to 2.91) (eTable 2 in Appendix). The global SDI was 0.66 in 2021; 8 regions (e.g., High-income Asia Pacific) had rates of DALYs that were higher than the global mean, whereas 13 regions (e.g., Tropical Latin America) had rates that were lower than the global mean (94.68) (Fig. 3C).

PD in All-Age: geographic regional trends

Incidence

In 2021, among 204 countries, China had the most cases of PD (508, 377; 95% UI, 430,499–592,748); Federal Republic of Germany had the highest incidence rate of PD (53; 95% UI, 51–55) (Fig. 4A and eTable 3 and eFig. 1 A in Appendix). Taiwan (EAPC, 6.22; 95%CI, 5.81–6.63) had the largest increases in PD incidence; Islamic Republic of Afghanistan (EAPC, -2.041; 95% CI, -2.33 to -1.75) had the largest decreases (eTable 3 and eFig. 2 A in Appendix). In 2021, Federal Republic of Germany (SDI, 0.90) had the highest incidence of PD, whereas Federal Republic of Somalia (SDI, 0.08) had the lowest incidence. The global incidence of PD in 2021 was 16.92(95% UI, 15.16–18.82); the incidences were above the global mean in 62 countries and below the global mean in 142 countries (eFig. 3 A in Appendix). China, India, United States of America, Japan, Germany, and the Russian Federation are the countries with the highest number of PD incidents, each exceeding 10,000 people. These nations collectively account for over half of the global PD toll (Fig. 4A).

Fig. 4.

Incident, Death, and Disability-Adjusted Life-Years (DALYs) Cases of PD in all-ages in 204 Countries and Territories. (A) Incidence; (B) Death; (C) DALYs

Mortality

In 2021, China had the highest number of PD associated deaths (92035; 95% UI, 75,907 − 108,133) (eTable 4 in Appendix and Fig. 4B). Principality of Monaco (20.41; 95% CI, 15.54–25.48) had the highest PD-associated mortality rate; United Arab Emirates (0.43; 95% CI, 0.34–0.51) had the lowest mortality rate (eTable 4 and eFig. 1B in Appendix). Republic of Albania (EAPC, 4.55;95%CI, 4.34–4.76) had the greatest increases in the mortality rate; the Islamic Republic of Afghanistan (EAPC, -2.78; 95%CI, -2.99 to -2.56) had the greatest decreases (eTable 4 and eFig. 2B in Appendix). In 2021, Principality of Monaco (SDI, 0.90) had the highest PD-associated mortality rate, whereas United Arab Emirates (SDI, 0.84) had the lowest mortality rate. The global PD-associated mortality rate in 2021 was 4.92 (95% UI, 4.40–5.29); the rates were above the global mean in 78 countries and below the global mean in 126 countries (eFig. 3B in Appendix). In China, India, America, Japan, Germany, and Russian Federation, PD has led to the highest number of deaths, exceeding 10,000 individuals in each country. This accounts for approximately half (55.08%) of the global mortality. Additionally, countries like Brazil, Italy, and Indonesia have also experienced significant numbers of deaths, with each surpassing 8000 individuals (Fig. 4B).

DALYs

In 2021, China had the highest number of PD associated DALYs (2,159,514;95% UI, 1,826,196-2,521,344). (eTable 5 in Supplement and Fig. 4C). Principality of Monaco had the highest rate of PD-associated DALYs (333.13; 95% UI, 267.52-396.18) (eTable 5 and eFig. 1 C in Supplement). Republic of Korea (EAPC, 4.34; 95% CI, 4.19–4.49) had the greatest increase in DALYs rate; the Islamic Republic of Afghanistan (EAPC, -2.88; 95%CI, -3.11 to -2.65) had the greatest decreases (eTable 5 and eFig. 2 C in Appendix). Principality of Monaco (SDI, 0.90) had the highest rate of childhood diabetes-associated DALYs; Republic of Madagascar (SDI, 0.40) had the lowest rate. The global rate of childhood diabetes associated DALYs in 2021 was 94.68 (95% UI, 85.37-103.11); the rates were above the global mean in 77 countries and below the global mean in 127 countries (eFig. 3 C in Appendix). In China, India, America, Japan, Germany, and Russian Federation, PD has led to the highest number of DALYs, exceeding 200,000 individuals in each country. This accounts for over half (55.08%) of the global DALYs. Additionally, countries like Brazil, Italy, and Indonesia have also experienced significant numbers of deaths, with each surpassing 100,000 individuals (Fig. 4C).

Percentage contributions of major risk factors to all-aged death of PD

Among all potential risk factors in GBD 2021, all aged PD death worldwide was primarily attributable to smoking [-7.73% (95%UI: -10.14 to -5.66)]. The percentage contribution of the protection factor to all aged PD death by SDI quintile, and GBD region were shown in eFig. 4 A and 4B. Specifically, smoking reduced 7.73% of all aged PD-associated deaths worldwide; Across SDI quintiles, the highest proportion was − 4.04% (Low SDI), and the lowest proportion was − 9.09% (Middle SDI); Among 21 geographical regions, the lowest proportion was − 12.58% (East Asia), and the highest proportion was − 1.6% (Western Sub-Saharan Africa). Notably, the proportion of all aged PD-associated mortality caused by Smoking was below the global mean in 2 regions. The global proportion of deaths attributable to risk factors increased from − 10.70 (95% UI, -13.61 to -7.94) in 1990 to -7.73% (95%UI: -10.14 to -5.66) in 2021 (eFig. 4 C). According to risk factors for different age groups, the highest proportion was − 2.69% (Over-95 age group), and the lowest proportion was − 9.09% (50–54 age group) (Fig. 5A). According to risk factors for different gender groups, the highest proportion was − 2.69% (Over-95 age group), and the lowest proportion was − 9.09% (50–54 age group) in male group (Fig. 5B); the highest proportion was − 1.34% (Over-95 age group), and the lowest proportion was − 4.15% (50–54 age group) in female group (Fig. 5C).

Fig. 5.

Proportion of Deaths attributable to risk factors at different ages. (A) Males and females; (B) Males; (C) Females

Percentage contributions of major risk factors to all-aged dalys of PD

Among all potential risk factors in GBD 2021, all aged PD DALYs worldwide was also primarily attributable to Smoking [-9.61% (95% UI: -12.22 to -7.09)]. The percentage contribution of the protection factor to all aged PD DALYs by SDI quintile, and GBD region were shown in eFig. 5 A and 5B. Specifically, smoking reduced 9.61% of all aged PD-associated DALYs worldwide; Across SDI quintiles, the highest proportion was − 4.53% (Low SDI), and the lowest proportion was − 11.71% (High-middle SDI); Among 21 geographical regions, the lowest proportion was − 15.15% (East Asia), and the highest proportion was − 2.03% (Western Sub-Saharan Africa). Notably, the proportion of all aged PD-associated DALYs caused by Smoking was below the global mean in 2 regions (eFig. 5B in Appendix). The global proportion of DALYs attributable to risk factors increased from − 12.67 (95% UI, -15.90 to -9.41) in 1990 to -9.61% (95% UI: -12.22 to -7.09) in 2021 (eFig. 5 C in Appendix). According to risk factors for different age groups, the highest proportion was − 2.76% (Over-95 age group), and the lowest proportion was − 18.37% (50–54 age group) (eFig. 6 A). According to risk factors for different gender groups, the highest proportion was − 4.96% (Over-95 age group), and the lowest proportion was − 28.01% (50–54 age group) in male group (eFig. 6B); the highest proportion was − 1.35% (Over-95 age group), and the lowest proportion was − 4.02% (55–59 age group) in female group (eFig. 6 C).

Factors influencing EAPCs

EAPCs significantly differed from incidence, and mortality rate in 2021; they significantly differed from SDI in 2021. EAPCs were positively correlated with rate of incidence (Pearson r = 0.41; P < 0.05) (eFig. 7 1 A in Appendix). The EAPC in incidence was also positively correlated with SDI (Pearson r = 0.52; P < 0.05) (eFig. 7 1B in Appendix). EAPCs were positively correlated with rate of mortality (Pearson r = 0.50; P < 0.05) (eFig. 7 2 A in Appendix). The EAPC in mortality was also positively correlated with SDI (Pearson r = 0.46; P < 0.05) (eFig. 7 2B in Appendix). EAPCs were positively correlated with rate of DALYs (Pearson r = 0.48; P < 0.05) (eFig. 7 3 A in Appendix). The EAPC in DALYs rate was also positively correlated with SDI (Pearson r = 0.48; P < 0.05) (eFig. 7 3B in Appendix).

Discussion

This study provided comprehensive and up-to-date global, regional, and national estimates of the PD burden based on the GBD 2021 data. The main findings are as follows: (i) generally, the all-age of incidence, death, and DALYs significantly increased from 1990 to 2021; (ii) the number of incident cases, deaths, and DALYs significantly increased, likely due to population growth and aging; (iii) males and the elderly generally experienced a heavier burden of PD compared to other demographic groups; and (iv) a substantial disease burden from PD remains, particularly in regions with high SDI levels. Our results reinforce findings from studies conducted between 1990 and 2021, which indicated that the burden of PD is increasing in some regions and countries worldwide [5, 26–28]. A global assessment of the epidemiologic patterns of PD may help policy makers and clinicians to develop appropriate prevention and management strategies.

Similar to GBD 2016 analysis of PD [5], the temporal trends in the all-aged incidence, DALYs, and death rates of PD varied significantly by SDI quintile. High SDI regions had a higher all aged incidence rate, while low SDI regions had lowered all aged incidence rate. A higher SDI signifies greater social development, increased aging, longer life expectancy due to better medical conditions, and higher exposure to risk factors from industrialization and urbanization. Overall, there is a positive correlation between improved health and socioeconomic status [33, 34]. Environmental factors linked to industrial development—such as pesticides, solvents, and metal elements, which are more common in high SDI countries—may contribute to the increased incidence of PD [35–38]. A study in the French suggested that persons living in the cluster with greatest vineyards density had 8.5% higher PD incidence. vineyards rank among the crops that require most intense pesticide use [38]. Additionally, individuals diagnosed with PD frequently experience extended survival attributed to concurrent health issues, which further complicates their overall well-being [39]. In high-income countries, the elderly population is increasingly affected by PD, a disease that may be caused by alterations at the cellular level, genetic influences and environmental degradation [40]. For example, China, a middle SDI country, has seen significant industrial growth since 1990. During this period, the incidence of PD across all age groups increased more than fourfold from 1990 to 2021, the largest rise globally. To meet the growing food demands of its expanding population, China has intensified agricultural development, leading to increased use and production of fertilizers and pesticides. As one of the leading producers of pesticides globally, China experiences a significant elevation in the risk of PD associated with the application and exposure to insecticides and herbicides [41].

In all metrics, including incidence, mortality, and DALY, males consistently outperformed females. The onset of PD generally occurs after the age of 65 for both genders, aligning with findings from earlier research [4, 42]. Nevertheless, approximately by the age of 90, a noticeable decline in these metrics is evident for both males and females. This reduction in burden is not inherently advantageous, as it frequently reflects deficiencies in health management among the elderly population. Commonly, when substantial challenges in self-care emerge, there is a lack of societal focus, inadequate resource allocation, and barriers to healthcare access, which includes shortcomings in diagnosis and insufficient medical treatment for various chronic illnesses and severe comorbidities. The precise mechanisms underlying this gender disparity remain ambiguous. Potential contributing elements may encompass higher levels of environmental and occupational exposures in males, whereas females might possess certain protective benefits attributable to variations in nigrostriatal circuitry and hormonal concentrations [43, 44].

A comprehensive analysis of DALY, incidence, and death data trends from 1990 to 2021 shows that the increase in incidence rate and a slight increase in DALY and death rate reflect advancements in healthcare and public health in global, high SDI, and middle SDI. Nevertheless, the increasing burden of DALY underscores the urgent need for enhanced long-term care strategies for patients with PD. It is essential to prioritize not just the prolongation of patients’ lifespans, but also the improvement of their quality of life and the mitigation of long-term disabilities linked to the illness. Consequently, it is essential for policymakers and professionals in public health to modify existing policies and allocate resources effectively in order to create holistic rehabilitation and long-term care strategies. This approach is necessary to guarantee that the extension of life is accompanied by an improvement in quality of life. This necessitates specialized training for healthcare personnel and the implementation of interdisciplinary management approaches to enhance cooperation among neurology, rehabilitation, and associated disciplines, particularly aimed at delivering personalized care for patients with various comorbid conditions. Attention should be directed towards minimizing workplace exposure and industrial pollution through the implementation of a robust environmental management system that encompasses rigorous standards and effective enforcement mechanisms. In nations with emerging economies, it is essential to strike a balance between economic development and environmental sustainability. This objective can be attained by advocating for environmentally friendly technologies and sustainable production methods, emphasizing industries that are characterized by low emissions and high energy efficiency, while also improving worker safety through adequate training and protective strategies. This approach integrates economic advancement with ecological conservation, placing human welfare at the core of development initiatives.

Consistent with the GBD 2016 analysis of PD [5], our results also indicated that smoking is negatively associated with the development of PD. Specifically, smoking appears to be more protective for men than for women. However, the PD risk in females remains lower than in males across all ages, including post-menopause, suggesting that the neuroprotective role of estrogen warrants further investigation. The study also revealed that former smokers who found quitting smoking to be “very difficult” had a 31% lower risk of developing Parkinson’s disease compared to those who found it “easy to quit” [23]. While the reduction in smoking prevalence in certain nations is a significant global health advancement, it may paradoxically lead to an increased occurrence of PD [45]. A study in the United States projected that the diminishing rates of smoking could lead to a 10% rise in the anticipated prevalence of PD by 2040, considering a presumed causal inverse relationship and a 10-year lag for the temporal impact of smoking on PD onset [46]. However, the exact duration between smoking exposure and its impact on PD risk remains unclear and may exceed a decade [47]. Thus, the timing regarding the possible influence of reduced smoking rates on PD incidence is still ambiguous. To comprehensively grasp the influence of evolving smoking behaviors on the incidence of PD, it is imperative to undertake additional research across diverse regions worldwide. Each region manifests unique smoking prevalence and temporal patterns, which may exert differential impacts on PD risk. Crucially, while probing into these associations, it is essential to reemphasize that the detrimental health effects of smoking significantly overshadow any potential benefits concerning PD.

Limitations

This research encountered several significant limitations that warrant detailed discussion. First, it heavily relied on the GBD database, which has its own constraints. The accuracy of this database is affected by the availability of national registry data, the significant number of undiagnosed PD cases, and a lack of comprehensive information regarding other risk factors associated with PD. Furthermore, potential risks linked to PD were not fully explored due to the limited data currently available. Second, using various datasets from the GBD database could introduce biases in assessing the burden of PD, as differences in research focus and quality might skew the results compared to actual data. There is also considerable uncertainty in the estimates, especially in areas where empirical data is scarce, which forces reliance on the compensatory estimates provided by the GBD study. Third, the study’s heavy dependence on linear regression modeling for calculating the EAPC may not be appropriate for all situations, potentially leading to biases. Lastly, the estimates derived from the data may suffer from increased regional inaccuracies due to the limitations of the data sources and the methodologies employed.

Conclusions

Over the past three decades, the global burden of PD has steadily increased, driven primarily by population aging. This trend is expected to persist, with males facing a higher risk of PD-related burden than females, and the risk escalating with age and over time. As the world transitions into an era of aging, the number and proportion of elderly individuals are rising across nearly all countries, likely amplifying the challenges associated with managing PD. The growing aging population, coupled with an increasing prevalence of contributing factors, underscores the urgent need to strengthen public health strategies and optimize resource allocation. Priority should be given to advancing research into the causes of PD, promoting early diagnosis, implementing preventive measures, and developing personalized treatment approaches to address this mounting global health challenge.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Author contributions

ZL, WK, and HPP designed and supervised the study. LYQ, DYL, and YLZX collected data and developed the database. LYQ and LZ conducted the analysis. LYQ and ZL were involved in manuscript writing. All authors reviewed and approved the manuscript.

Funding

This study was supported by the National Natural Science Foundation of China, Grant/Award Numbers: 82471271, 82171917, 81971689, 82090034.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

This research adhered to the ethical guidelines established by the governing authority of the 2021 Global Burden of Disease database. Since the study utilized publicly accessible, de-identified data, it did not necessitate further ethical approval.

Consent for publication

This study utilized data from publicly available databases, which do not contain identifiable personal information. Therefore, consent for publication is not applicable.

Competing interests

The authors declare no competing interests.