Validation of Parkinson's Disease-Related Questionnaires in South Africa

Background There are very few epidemiological studies investigating Parkinson's disease (PD) in Africa. The hundreds of local languages and dialects make traditional screening and clinical evaluation tools difficult to use. Objective The objective of the study was to validate two commonly used PD questionnaires in an African population. Methods The PD Screening Questionnaire (PDSQ) and Parkinson's Disease Questionnaire (PDQ-39) were modified and translated into Afrikaans, Setswana, and isiZulu and administered to a sample of healthy local residents. We assessed the internal consistencies and cluster characteristics of the questionnaires, using a Cronbach's alpha test and exploratory factor analysis. The questionnaires were then administered to a population-based sample of 416 research participants. We evaluated the correlations between the questionnaires and both a timed motor task and the Unified Parkinson's Disease Rating Scale motor subsection 3 (UPDRS3), using locally weighted scatterplot smoothing (LOWESS) regression analysis and Spearman's rank correlation. Results Both questionnaires had high overall internal consistency (Cronbach's alpha = 0.86 and 0.95, respectively). The modified PDQ-39 had evidence of five subscales, with Factor 1 explaining 57% and Factor 2 explaining 14%, of the variance in responses. The PDSQ and PDQ-39 scores were correlated with the UPDRS3 score (ρ = 0.35, P < 0.001; and ρ = 0.28, P < 0.001, respectively). Conclusion The translated PDSQ and PDQ-39 questionnaires demonstrated high internal consistency and correlations with clinical severity of parkinsonism and a timed motor task, suggesting that they are valid tools for field-based epidemiological studies.


Introduction
e global impact of Parkinson's disease (PD) is expected to reach pandemic proportions with the aging of both developed and developing country populations [1][2][3][4]. As life expectancy on the African continent increases, neurodegenerative diseases are becoming a growing public health concern. Population-based epidemiological studies of neurodegenerative disease in Africa are rare, and there are limited data from the 21 st century [5]. Screening tools designed and validated in the developed world, primarily in English, are not appropriate for much of Africa where there are hundreds of local languages and dialects [6], making screening for PD or parkinsonism using questionnaires validated in countries such as the USA and the UK challenging.
South Africa has the second largest economy in Africa [7] and a predominantly black population with increasing life expectancy [8]. e country has a dynamic academic and healthcare environment and the skills and infrastructure to conduct world-class scholarly activities and provide modern healthcare services. ere are 11 official languages, and PD researchers must address this barrier in order to conduct quality Parkinson's disease (PD) research in South Africa. e questionnaires used in developed countries are usually self-administered in English. However, in the South African setting, due to language and literacy challenges, the questionnaires are administered by field workers and are thus subject to misinterpretation when translated. Similarly, some questions do not easily translate from English, and several concepts are not easily translated into African languages.
To ensure that the questions are clear and unambiguous to study participants, it is essential that the English versions be modified, translated into, and validated in vernacular languages where relevant. Failure to do this limits our understanding of disease burden and isolates large populations from the drug development process, in which drugs may perform differently than in predominantly white English-speaking populations in developed countries.
We validated two commonly used PD questionnaires: a PD Screening Questionnaire (PDSQ) [9] and the 39-item questionnaire that assesses self-reported PD-specific healthrelated quality of life over the last month (PDQ-39) [10], to screen research participants in a field-based epidemiological study of the relationship between environmental manganese (Mn) exposure and parkinsonism. e study population resides near one of the largest Mn smelters in the world. We report the modification and validation of these two questionnaires in English and three of the most commonly spoken languages in South Africa: Setswana, isiZulu and Afrikaans.

Methods
e Human Research Ethics Committee of the University of the Witwatersrand (ethics clearance certificate no. M141153) and the Human Research Protection Organization of Washington University approved the study. e PD Screening Questionnaire comprises nine questions to elicit self-reported symptoms typical of PD to screen populations for PD, answered as "yes" or "no." It has been widely used in epidemiological studies. e PDQ-39 is a validated PD-specific quality of life questionnaire comprised of 39 questions that assess mobility, activities of daily living, emotional well-being, stigma, social support, cognitions, communication, and bodily discomfort in patients with PD. Answers are based on a 5-point Likert scale (never, occasionally, sometimes, often, and always or cannot do at all). e UPDRS3 quantifies motor features of PD on a 0-108 scale with higher scores indicating more severe parkinsonism.
We used a three-step validation process to validate the two questionnaires: translation and face validity, content validity, and construct validity.
In the first step, we modified and translated several questions in the English versions of the questionnaires, in accordance with methods described by Aaronson et al. [11]. e questions were modified without changing the information they attempt to elicit, in order to make them understandable to English-speaking South Africans, in terms of both language and content. e modified questionnaires were reviewed for accuracy and appropriateness, after which individuals proficient in three of the most common South African languages (Setswana, isiZulu, and Afrikaans) then translated them. e questionnaires were back-translated by different individuals, also proficient in the respective languages.
In the second step (content validation), we tested the performance of the translated questionnaires in 16 English-, Afrikaans-, Setswana-/Sotho-, and isiXhosa-/isiZulu-speaking male and female volunteers with varying educational achievements. Setswana and Sotho are linguistically similar and have similar origins, as have isiXhosa and isiZulu which are both Nguni languages. Interviewers who were fluent in the relevant languages were trained by skilled qualitative researchers to administer the questionnaires, face to face. e interviewers recorded participants' responses to each question and asked them to clarify their thought processes in order to elicit what they understood by each question. Probing was used to obtain a detailed narrative of the cognitive process of each participant before he/she answered a question. e interviews were audiorecorded, transcribed verbatim, and translated into English. Based on the results of these cognitive interviews, minor changes were made to the questionnaires. For example, in almost all South African vernacular languages, there is no single word for "balance". us, in the PDSQ, the question "Is your balance poor?" was changed to "Is your balance poor when walking?". e two questionnaires were then administered to a convenience sample of 160 individuals, older than 40 years, from a residential area in the Midvaal region of South Africa, who spoke one of the four languages (40 per language) to assess the internal consistency of the questionnaires and to determine if the PDSQ and PDQ-39 retained their item cluster characteristics.
In the third step (construct validity), we administered the questionnaires, face to face, to 416 participants in a population-based study of the health effects of environmental Mn exposure. All participants were older than 40 years and were local residents, living near a ferromanganese smelter. Local, trained fieldworkers recruited study participants, using a random household sampling method. Performances on the PDQ-39 and PDSQ were validated against two methods of assessing motor function: (1) a Purdue Grooved Pegboard timed test [12] was used to measure fine motor speed and visuomotor coordination (times taken to complete the task with the dominant and nondominant hand were recorded), and (2) the Unified Parkinson's Disease Rating Scale motor subsection 3 (UPDRS3) [13] was administered by a movement disorders specialist without knowledge of the responses in either questionnaire. e tests and tools are described in Supplementary Table S1.

Statistical Analysis.
We performed all statistical analyses using Stata MP version 14.2 (StataCorp LP, College Station, Texas). e internal consistencies of both the PDSQ and the PDQ-39 were assessed using a Cronbach's alpha test; internal consistency was considered acceptable when α > 70, based on the 160 completed questionnaires. For the PDQ-39, we calculated the internal consistency of the eight subscales in the original questionnaire. To determine if the two questionnaires retained their original subscale structures (one for PDSQ and eight for PDQ-39), we used exploratory factor analysis with an orthogonal rotation (Varimax) to explore how many factors the items loaded onto the modified and translated versions of the questionnaires. Exploratory factor analysis provides procedures for determining an appropriate number of factors and the patterns of loadings from the data [14]. We used an eigenvalue >1.0 as the threshold for a domain (i.e., subscale) [15][16][17]. We then recalculated the internal consistency of the five subscales that were identified through the exploratory factor analysis.
To investigate the association between UPDRS3 scores and age, grooved pegboard times (dominant and nondominant hand), PDQ-39 score, and PDSQ score, we first graphically evaluated these associations using locally weighted scatterplot smoothing (LOWESS) regression analysis. We also compared the performance of the PDSQ in relation to the PDQ-39. We again graphically evaluated this association using LOWESS regression analysis and evaluated correlations using Spearman's rank correlation, with significance at α = 0.05.

Results
e demographic characteristics of the study participants in the content and construct validity steps are described in Table 1. In both the content and construct validity components, the majority of study participants were female (61.5% and 58.9%, respectively). e mean ages of the two study populations were 50.9 ± 10.0 (range 33-79) years and 51.2 ± 9.4 (range 38-97) years, respectively. e mean UPDRS3 score of those who participated in the construct validity component (N = 416) was 10.1 ± 7.8 ( Table 2). e range of scores associated with the PDSQ and the PDQ-39 was wide (0-52). Participants with higher UPDRS3 scores were older (ρ = 0.30, P < 0.001) and took longer to complete the grooved pegboard test (dominant hand ρ = 0.39, P < 0.001; nondominant hand ρ = 0.39, P < 0.001). e mean PDSQ score was 0.63 ± 1.85 for the Englishspeaking participants, 0.73 ± 1.47 for the Afrikaans-speaking participants, 2.48 ± 2.99 for the Setswana-speaking participants, and 3.15 ± 3.47 for the isiZulu-speaking participants. e differences were statistically significant (F = 8.41, P < 0.001). Factor analysis for the modified PDSQ demonstrated loading on one factor (eigenvalue 3.81), consistent with assessing a single clinical domain. e PDSQ had high overall internal consistency (Cronbach's alpha = 0.86); the individual questions also demonstrated high internal consistency (Cronbach's alpha range = 0.83-0.86), suggesting that a participant's response to one question was related to his/her response to other questions in the PDSQ (Table 3) (1) mobility, out-of-house, and activities of daily living; (2) emotional well-being; (3) cognitivecommunication-body discomfort; (4) activities of daily living inside the house (ADL); and (5) items relating to eating and drinking in public, problems in relationships, and unintentionally falling asleep (Table 4). e modified and translated PDQ-39 questionnaire demonstrated high overall internal consistency (Cronbach's alpha = 0.95). However, the individual subscales had variable internal consistency (Table 5). Subscales for mobility (α = 0.9), activities of daily living (α = 0.82), emotional well-being (α = 0.9), and body discomfort (α = 0.83) demonstrated good to excellent internal consistency. Social support (α = 0.78), cognition (α = 0.79), and stigma (α = 0.74) had acceptable internal consistency. Communication (α = 0.69) demonstrated marginal internal consistency. e UPDRS3 scores were positively correlated with both the PDSQ (ρ � 0.30; P < 0.001) and the PDQ-39 (ρ � 0.22; P < 0.001) scores, indicating that, in general, those with more severe parkinsonism had more PD symptoms and poorer PD-specific health-related quality of life (Figure 1). e PDQ-39 and PDSQ scores were strongly correlated (ρ � 0.64; P < 0.001) (Figure 1).

Discussion
In this multistep validation study, we demonstrated that the two questionnaires (the PDSQ and the PDQ-39) retained their original meanings and had good internal consistency once modified and translated for the most common South African languages. Moreover, we demonstrated strong correlations between severity of parkinsonism and PD symptoms as well as PD-specific health-related quality of life, suggesting that the questionnaires performed as expected when compared to a clinical measure of severity. e PDSQ was originally designed for use in epidemiological studies to identify people with PD, due to the high cost of this expert assessment in large populations [18]. While the purpose of the population-based study focuses on identifying parkinsonism in an environmentally exposed population, the PDSQ performed as expected, given that the number of affirmative answers was positively associated with the UPDRS3 score. e modified PDQ-39 also demonstrated good internal consistency and was strongly correlated with motor signs of parkinsonism in the population-based study (the PD-specific questions were omitted). Overall, we provided evidence that these two modified questionnaires are valid screening tools for use in field-based epidemiological studies and may augment data obtained from a clinical specialist's examination. e use of the PDSQ questionnaire in the populationbased study is largely consistent with the original, intended use of this tool as a screening questionnaire in epidemiological studies. However, we used parkinsonism as a continuous measure of a health outcome, as opposed to a diagnosis of PD.
is approach is better suited to investigating associations between motor signs of parkinsonism and environmental exposures in populationbased studies of adults. A recently published study in Xhosa-speaking South Africans found that only 18% of the participants could correctly identify a patient with PD from a video [19]. Although we focused on Setswana-and isiZulu-speaking South Africans, PD awareness in these groups is likely to be similar. Nevertheless, the symptoms in the modified PDSQ appeared to be recognized by the participants, and those with higher scores on the PDSQ tended to also have higher UPDRS3 scores. Further research is needed to determine if these modified African   language questionnaires have sufficient sensitivity and specificity to be used as screening questionnaires to identify those with PD. However, in this environmental health research setting, the questionnaires performed well. While our study is not the first to attempt to validate the PDQ-39 in non-English languages, our aim to determine the association between an environmental exposure-and PDspecific quality of life is unique. We previously demonstrated higher scores on the PDQ-39 in those with occupational Mn exposure and UPDRS3 ≥ 15 [20]. In this environmental Mn exposure study, we found similar associations between the modified PDQ-39 and severity of parkinsonism, demonstrating a consistency across different Mn-exposed populations. While the modified PDQ-39 retained the anticipated association with parkinsonism, the clustering of questions (subscales) differed from the original British version of the questionnaire [10]. Interestingly, a validation study in which the PDQ-39 was modified from British English to American English also changed the questionnaire item cluster characteristics, finding that mobility-stigmacognition, ADL-communication-body discomfort, and well- Parkinson's Disease 5 being-social support clustered together [21]. Overall, the agreement between the subcategories of the PDQ-39 was excellent, but social support, stigma, and communication were outliers, potentially due to ethnic differences in our study population. For example, questions categorized as stigma and social support in the British and American versions of the questionnaire had a very different context for the black South African research participants. Older black South Africans often live with extended families and might not need support from a spouse/partner, which might influence the relationships between questions. e stigma questions were not asked unless the study participant said that he/she had a diagnosis of PD; this might have impacted the agreement with the rest of the questionnaire. In addition, very few study participants indicated that they had been diagnosed with PD, which could also have reduced the internal reliability. e questions about stigma might not be essential in population-based epidemiological studies. e reason for communication demonstrating poorer agreement with the other variables is less clear. e use of the word "people" in two of the three questions in this subcategory might be too broad. Communication entails interacting beyond the realm of friends and family. English and Afrikaans are spoken by more than half of the larger community in the study area (approximately 54%) [22], most of whom are white, and are the primary languages used in the workplace. Many of the study participants spoke neither language. e obstacle of language, when communicating with the general public, is not uncommon for those with low education levels and for those educated in schools where English is not the language of instruction. Despite the overall good performance of the modified questionnaires in this South African population-based study, the study had some limitations. e internal consistency of the PDSQ differed across the four languages, and more adaptations might be required before it is used in population-based studies. For example, there might be overreporting of symptoms (e.g., smaller handwriting) due to low literacy rather than neurological problems. e PDQ-39 scores were lower for English and Afrikaans speakers, which could be an indication of literacy rather than quality of life; English and Afrikaans speakers might be better educated and more literate than those who are not fluent in either language. e use of the PDQ-39 in this screening context is nontraditional and beyond the original intent of the questionnaire. However, the strong correlation with a clinically meaningful motor examination from a movement disorders specialist provides compelling evidence that the questionnaires are measuring PD-specific effects on quality of life. While other validation studies of these questionnaires were performed in general population samples, there is also substantial evidence that the PDQ-39 is a valid measure of the impact of PD on quality of life in patients with PD [23][24][25]. e fact that our study participants were not PD patients might explain some of the differences between our study findings and previous reports.
In summary, our study provides strong evidence that the modified PDQ-39 is suitable for use in epidemiological studies investigating parkinsonism in English-, Afrikaans-, Setswana-, and isiZulu-speaking South African communities, while the PDSQ might need to be further modified before it can be used. Further validation in PD patients whose primary languages are Afrikaans, Setswana, and isiZulu will be necessary before the questionnaires can be recommended for use in clinical practice.