Background: Parkinson’s disease (PD) is one of the most common neurological disorders that mostly affect aged individuals. The common symptoms of PD are rest tremor, bradykinesia, and rigidity. Objectives: The present study was devised to find out the clinical features and risk factors associated with PD in a population of Khyber Pakhtunkhwa. Methods:A total of 600 PD patients and 1,200 control individuals took part in this study. The participants filled out a standard questionnaire. Results: This study found a significant association between PD and exposure to pesticides (p < 0.0001) and doing work on farms (p < 0.0001). The use of aldrin was significantly associated with PD (p < 0.0001). Furthermore, we also found that PD status was associated with individuals who have a history of depression, hypertension, head injury, and Alzheimer’s disease. This study also showed that the PD rate was lower in those who were using tobacco products. Conclusion: In this case-control study, we revealed some environmental and medical conditions that are linked with PD. To control the disease, we must minimize exposure to pesticides, and the government and scientific community should play their role.

  • According to an estimation, one million people have Parkinson’s disease (PD) in Pakistan, and this number will increase up to 1,200,000 till 2030.

  • Both non-modifiable (age, gender) and modifiable risk factors such as occupation, exposure to pesticides, and depression have an association with PD.

  • PD is under research in Pakistan, and there is a need to identify the factors that increase the risk of PD.

  • The disease rate was higher in rural areas compared to urban areas.

  • The odds of developing PD was lower in smokers and people having exposure to tobacco products. In drivers, the disease rate was significantly lower, while in farmers, this rate was significantly higher. Moreover, the disease rate was higher in individuals having exposure to aldrin. Furthermore, this study also revealed the association between PD and exposure duration to risk factors.

  • The disease rate was higher in individuals having depression, hypertension, or a familial history of PD.

  • In Pakistan, levodopa therapy is commonly used to treat PD patients.

After Alzheimer’s disease, Parkinson’s disease (PD) is the most common neurological disorder that affects millions of people worldwide [1]. PD is mainly marked by tremor, stooped posture, and bradykinesia; the combination of these symptoms is known as parkinsonism. Although these symptoms may not be present in the early stage of the disease, as the disease progresses, they are more prevalent [2]. Every decade, the number of nigral cells is reduced from 4.7–6% in the normal human brain [3].

PD may be genetic or sporadic, but currently, sporadic cases account for about 90% of cases. However, it is well known that sporadic PD risk is determined by the complex interplay of genetic and environmental risk factors. Several studies have discussed the environmental risk factors of PD [4]. Factors such as head injury, pesticide exposure, and anxiety diary product have a positive association with PD, while smoking and coffee and alcohol consumption have an inverse relation with PD [5]. Furthermore, rural living [6], drinking well water [7], and nutritional factors [8] have been reported with PD. The association of pesticide exposure in PD has long been suspected, but the mechanism and specific causative agents are not well understood. However, some studies have reported that short-term or long-term exposure of pesticides such as dieldrin, paraquat, maneb, and pyrethroids has a positive association with PD [9].

In view of the critical importance of the disease, it requires a better understanding of this common disorder. In particular, determining which environmental risk factors are associated with the disease may allow us to design better control methods. We have designed the present study to find out the clinical features and associated risk factors with PD in a population of Khyber Pakhtunkhwa (KPK), Pakistan.

Study Area

This hospital-based study was carried out at Lady Reading Hospital, Peshawar, KPK, Pakistan. KPK is the 3rd largest province of Pakistan by the economy and population size. However, geographically, it is the smallest [10]. The total area of KPK is 101,741 km2, with a total population of 35,252,047 [11]. Life expectancy in Pa­kistan is 66.5 (male: 65.7; female: 67.4) [12]. The literacy rate in KPK is 88.6% [13].

Study Design

Before initiation of the study, a consent form was signed by the subjects, and formal approval was obtained from the institutional bioethical committee of Hazara University, Mansehra. The study duration was 12 months (September 1, 2017, to September 1, 2018). The inhabitants of KPK aged 18 years or above were included in this study. Both new cases and previously diagnosed cases were included in this study. A case was defined as a PD patient diagnosed by neurologists according to the UK Parkinson’s Disease Society Brain Bank criteria [14], and we found 655 patients to have PD. Among the 655 PD patients, 600 patients were included. Among 1,233 eligible control individuals, 1,200 agreed to take part. Control groups belonging to KPK province were selected in this study; individuals from other provinces were excluded. The members of the control group were neither linked to one another nor PD patients. The controls were defined as the individuals of the same regions that reproduced cases, but they did not have PD. Both the cases and controls were statistically matched. Two controls were matched to each case by residence and gender. Most of the participants were from the rural area of KPK (Fig. 1).

Fig. 1.

Distribution of patients and controls in KPK.

Fig. 1.

Distribution of patients and controls in KPK.

Close modal

The demographic characteristics of cases and controls are described in Table 1. The cases group included 132 (22.0%) female and 468 (78.0%) male subjects, and control subjects were comprised of 300 (25.0%) female and 900 (75.0%) male subjects.

Table 1.

Demographic characteristics of PD cases and control subjects

 Demographic characteristics of PD cases and control subjects
 Demographic characteristics of PD cases and control subjects

We designed two standard questionnaires for this study. The first questionnaire includes demographic information and risk factors (for all participants), while the second questionnaire was about clinical features and risk factors of PD (only for patients). The participants filled out and signed the consent form. A face-to-face interview was held for individuals who did not understand the questionnaire.

Statistical Analysis

Data were coded and analyzed by using SPSS version 20.0 [15]. Statistical analysis was divided into three parts: descriptive analysis was used for demographics, clinical features of PD patients, exposure duration to the risk factors, and medicine prescription, while logistic regression (95% confidence interval) and χ2 tests were used to investigate the importance of different variables. pvalue ≤0.05 was considered statistically significant.

Demographics, clinical features, and medicine prescriptions are described in percentages. For the dichotomous variable comparison of cases and controls, χ2 tests, and logistic regression (95% confidence interval) were used.

This study included a total of 1,800 participants (600 patients and 1,200 controls). Most of the patients were from Peshawar (44%) and Swat (20%). The distribution of PD patients from different districts is shown in Figure 2. The most common and effective treatment used to treat PD patients was carbidopa/levodopa therapy with the other combination. Sinemet (carbidopa/levodopa) in combination with Pk-Merz (amantadine HCl) and Kempro (procyclidine HCl) was prescribed to 48.0% patients. Sinemet, Pk-Merz, and Nuberal forte (orphenadrine) were used by 23.0% of patients, while 13.00% of patients were using Evion (tocopherol Vit E), Cecon (ascorbic acid), Sinemet, Pk-Merz, and Motilium (domperidone) (Table 2).

Table 2.

Medicine combination prescribed to patients

 Medicine combination prescribed to patients
 Medicine combination prescribed to patients
Fig. 2.

Distribution of PD patients in districts of KPK.

Fig. 2.

Distribution of PD patients in districts of KPK.

Close modal

To determine the clinical feature of PD patients, the neurologists observed the patients. The most common clinical features were rest tremor (97%), followed by trouble in buttoning buttons (96%), poor balance (84%), freezing of gait (83%), muscular rigidity (80%), soft voice (79%), change in handwriting (72%), and change in facial expression (70%). The prevalence of other clinical features was less than 70% (Table 3).

Table 3.

Clinical features of Parkinson’s disease

 Clinical features of Parkinson’s disease
 Clinical features of Parkinson’s disease

Questionnaires were filled out by the patients and controls to determine the association of PD with the use of tobacco products, pesticide exposure, and use of tea or coffee. Table 4 signifies that the odds of developing PD was higher in individuals having exposure to pesticides (OR: 4.52). The risk of developing PD was less in cigarette smokers (OR:0.25) and snuff (chewable tobacco) users (OR: 0.44).

Table 4.

Association of pesticides, tobacco products, tea, and coffee with PD

 Association of pesticides, tobacco products, tea, and coffee with PD
 Association of pesticides, tobacco products, tea, and coffee with PD

To determine if there is any association between PD and occupation, the occupation was collapsed into twelve categories. This study exposed that the risk of developing PD was higher in farmers (OR: 4.32), while this risk was lower in drivers (OR: 0.30). We found no significant risk of developing PD among laborers (OR: 0.73), government servants (OR: 0.81), shopkeepers (OR: 0.69), housewives (OR: 1.33), and students (OR: 0.66) (Table 4). After finding a significant association between PD and the use of pesticides and insecticides, we further asked the cases and controls about the type of pesticides and insecticides they used. Among all the pesticides and insecticides, we found that aldrin was significantly associated with PD (p < 0.0001) (Table 5).

Table 5.

Occupational risk factors of Parkinson’s disease

 Occupational risk factors of Parkinson’s disease
 Occupational risk factors of Parkinson’s disease

We further studied the exposure duration of risk factors that have a significant association with PD. We found that patients have more exposure (years) to pesticides compared to controls. Also, a patient’s exposure to pesticides (days/year) was higher compared to the control group. Moreover, patients have more exposure duration to aldrin compared to the control group (Table 6). The current study also revealed that the control group was smoking more often compared to the patients. Furthermore, the use of other forms of tobacco, such as snuff (chewable tobacco), was more frequent in the control group compared to patients (Table 6). This study further revealed that the duration of farming has a direct relation with PD, while driving has an inverse association. (Table 6).

Table 6.

Exposure duration to risk factors

 Exposure duration to risk factors
 Exposure duration to risk factors

To study the association of PD and other major illnesses, the patients and controls were asked about their medical history. This study revealed a significant association between PD and some health problems, including depression (p < 0.0001), hypertension (p < 0.0001), head injury (p = 0.036), and Alzheimer’s disease (p = 0.036), while no significant difference was found in patients with other medical conditions including stroke, encephalitis, and hydrocephalus (Table 7).

Table 7.

Health problems associated with Parkinson’s disease

 Health problems associated with Parkinson’s disease
 Health problems associated with Parkinson’s disease

This is the first case-control study from KPK, Pakistan, that revealed the association of PD with different risk factors. In this study, we aimed to investigate the clinical features of PD and the association of PD with environmental risk factors and medical conditions. In this study, we also provide information about the prescription to PD patients.

Despite numerous attempts to identify specific biomarkers, the diagnosis of PD is yet based on clinical criteria that include a motor feature (postural instability, tremors, bradykinesia, and freezing of gait) and several non-motor features. Levodopa therapy is still widely used to treat motor symptoms of PD [16]. In the current study, we also showed that tremors, bradykinesia, postural instability, and freezing of gait are common clinical features in PD patients, while levodopa is commonly used to treat PD patients. The disease rate was higher in the rural population as in Pakistan, most of the people in the rural area depend directly or indirectly on agriculture.

There is a strong association of environmental factors with the increased incidence of PD. Working on farms and exposure to pesticides is the primary class of environmental agents that increase the risk of PD that are intentionally used to eliminate pests. A study has shown that DDT, DDE, dieldrin, and aldrin have a similar structure and increase the risk of developing PD [17]. In the present study, we looked for the association between PD and working on farms. We also observed an association between PD and pesticide exposure. The logistic regression revealed a significant association between PD and working on farms and exposure to pesticides. We further found that exposure to pesticides was more frequent in patients than controls. Another case-control study also observed a significant association between PD and exposure to pesticides [18]. To further study the association of PD and pesticide exposure, we asked the participants about the particular pesticides. Among all the pesticides, a significant association was found between PD and exposure to aldrin. Moreover, the patient’s exposure was more often to aldrin compared to controls. Another case-control study reported that increased dieldrin and β-HCH may be linked with the risk of PD [19]. Furthermore, mice exposed to DDT or DDE failed to show nigrostriatal damage evidence or behavioral abnormalities [20]. Although this study found that long-term exposure increases the risk of PD, a recent study showed that a very low level of agricultural chemicals could boost the risk of PD. A study from the patient-derived stem cell PD model showed that through oxidative modification of microtubules, mitochondrial transport is disrupted even with low doses of PQ/MB or Rot. Moreover, exposure to agricultural chemicals arrests mitochondrial transport in PD neurons [21]. Our study also revealed a significant association of PD with other medical conditions, including depression, hypertension, head injury, and Alzheimer’s disease. A recent study also reported a high depression rate in PD patients [22]. Hypertension and PD have a significant association with age. Hypertension may damage blood vessels in basal ganglia that contain striatum and substantia ni­gra. A meta-analysis study also reported that hypertension might increase the risk of PD [23]. Another meta-analysis also reported a significant association of depression with a subsequent risk of PD [24]. Moreover, a significant association was also reported between head trauma and PD [25]. Our study further revealed that the use of tobacco products is inversely associated with PD. Our findings are consistent with previous reports, which showed that smoking might be protective against PD [26].

The present study sheds light on understanding the epidemiology of PD in the KPK population. Moreover, this study also provides information that a large population of KPK has exposure to risk factors, such as pesticides, depression, and hypertension, which renders the study important in understanding which of these factors leads to an upsurge of PD in this population and developing the appropriate prevention strategy. However, our research has some limitations, such as small sample size. Although this sample size is enough for the common exposure, it does not provide enough power for the association of PD with rare risk factors. But, giving the fact that KPK is a small province and PD is not a common disease in the KPK population, a larger sample size was almost impossible.

In conclusion, this study revealed that the odds of developing PD increase with an increase in the age group. This study also found a significant association between PD and working on farms and exposure to pesticides. This study also suggests minimizing exposure to pesticides. We also suggest further research to reveal the reason behind the strong association of PD with other medical conditions. A national survey is recommended to find out the prevalence rate in the whole country, and there is a keen need for awareness in the people of KPK about PD, and for this purpose, government and social sectors, especially the scientific community, should play their role.

The author is thankful to Prof. Adnan Khan, Dr. Saad Ali, Dr. Aisha Zafar, Dr. Kashif Khan, and all members of the neurology team (Lady Reading Hospital) for their cooperation.

A consent form was signed by the subjects, and ethical approval was obtained from Hazara University, Mansehra.

The author has no conflict of interest.

None.

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