Neuroepidemiology of Parkinson’s disease in an urban area of Iran : from screening and prevalence to nutritional, clinical and psychiatric features and quality of life

Abstract: Background. Parkinson’s disease (PD) is the second most common neurodegenerative disorder with complex presentations consisting of different motor and non-motor symptoms. The multisystem and progressive nature of PD has made it a complicated entity with broad variation in manifestations and reciprocal effects on several aspects of daily life. Aims. This doctoral thesis investigated different neuroepidemiologic aspects of PD and parkinsonism including its screening and prevalence in the urban area of Tehran, Iran, nutritional status and risk factors for malnutrition, clinical and psychiatric features, healthrelated quality of life (HRQoL) and its determinants in Iranian PD patients. For this purpose, we also aimed to validate several questionnaires and make a new screening instrument. Study I. Psychometric properties of the Persian-translated version of the short-form Parkinson’s disease questionnaire (PDQ-8) were assessed in 114 Iranian patients with PD consecutively recruited from an outpatient Movement Disorder Clinic. The Cronbach’s alpha coefficient of the entire PDQ-8 was 0.740 (95% CI: 0.661-0.806). Replacement of PDQ-8 items with other questions with the highest internal consistency within each dimension of the long-form PDQ (PDQ-39) did not further improve reliability. The Persian version of the PDQ-8 was shown to be a valid and reliable instrument to assess HRQoL in Iranian PD population especially in mental and behavioral aspects. PDQ-8 is a practical and informative instrument in daily clinical practice where clinicians are in shortage of time and need a validated self-reported brief questionnaire. Study II. To develop a new instrument for screening of parkinsonism in community-based surveys, a comprehensive questionnaire consisting of 25 items on different PD symptoms was filled in 157 patients with parkinsonism and 110 controls. Using the concept of clinical utility index (CUI), six items on “stiffness & rigidity”, “tremor & shaking”, “troublesome buttoning”, “troublesome arm swing”, “feet stuck to floor” and “slower daily activity” demonstrated good validity (CUI≥0.64) to be included in the new screening tool . We introduced a new set of six items to screen parkinsonism, which showed higher diagnostic values [area under curve (AUC)=0.977] compared to the previously developed questionnaires. This new instrument could be used in population-based surveys to screen parkinsonism in poor-resource settings. Study III. Following a random multistage sampling of the households within the network of “Health Centers” with 374 subunits in all 22 urban districts of Tehran, 20,621 individuals answered the baseline checklist and the screening questionnaire developed in study II. Data from 19,500 persons aged ≥30 years were entered in the final analysis. A total number of 157 cases were positively screened for parkinsonism that resulted in age- and sex-adjustment prevalence rates of 222.9/100,000 (95% CI: 160-300) and 285/100,000 (95% CI: 240-329) based on the real Tehran population and “WHO World Standard Population”, respectively. The male/female ratio of probable parkinsonism was 1.62 and there was a steady increase by advancing age. The calculated rates for the prevalence of parkinsonism in our study are closer to the reports from some European and Middle-East countries, higher than reports from the Eastern Asian and African populations, and lower than Australia. The prevalence rate of>200/100,000 for parkinsonism in Tehran, Iran is considered as a medium-to-high rate. Study IV. Nutritional status was evaluated in 143 Iranian PD patients and 145 age- and sexmatched controls by means of the validated Persian version of the mini-nutritional assessment (MNA). The mean of total MNA score was not significantly different between the two groups [24.4 (SD=3.8) in controls vs. 25.1 (SD=3.4) in PD patients, p=0.094]. Three (2.1%) PD patients were suffering from malnutrition and another 37 (25.9%) were at risk of malnutrition; while in control group similar feature was observed (2.0% malnourished and 35.2% at risk of malnutrition, p=0.228). Our findings indicated similar nutritional status among mild-to-moderate PD patients and matched controls from the same community. However, nearly one third of PD population were either malnourished or at risk of malnutrition necessitating more attention towards nutritional assessment in PD. Study V. Factors affecting nutritional status were investigated in 150 PD patients including a comprehensive list of motor and non-motor scales. The total score of the Unified Parkinson's disease rating scale (UPDRS) scale (r=-0.613, p<0.001) and PD duration (r=-0.284, p=0.002) had a significant inverse correlation with the total MNA score. A higher Hoehn and Yahr stage [2.5 vs. 2.0, p<0.001], more severe anxiety [8.8 vs. 5.9, p=0.002], depression [9.0 vs. 3.6, p<0.001] and fatigue [5.4 vs. 4.2, p<0.001] were observed in PD patients with nutritional insufficiency. Except for stigma, all other domains of the HRQoL significantly correlated with the total MNA score. We showed that disease duration, severity of motor and psychiatric symptoms (depression, anxiety) and fatigue associated with nutritional status in PD, which itself affected different aspects of HRQoL especially the emotional well-being and mobility. Study VI. A broad spectrum of demographic, motor and non-motor characteristics were evaluated in 157 PD patients consisting of comorbidity profile, nutritional status, UPDRS (total items), psychiatric symptoms (depression, anxiety), fatigue and psychosocial functioning through physical examination, validated questionnaires and scales. Structural equation model (SEM) and multivariate regressions were applied to find determinants of Parkinson’s disease severity index (PDSI) and different domains of HRQoL (PDQ-39). Female sex, anxiety, depression and UPDRS-part II scores were the significant independent determinants of PDSI. A structural model consisting of global motor, global non-motor and co-morbidity indicator as three main components was able to predict 89% of the variance in HRQoL. However, outstanding heterogeneities in the pattern and determinants of HRQoL were found among different PD phenotypes. Conclusions. We showed a medium-to-high prevalence rate for suspicious parkinsonism in Iranian population living in the urban area of Tehran by means of a novel 6-item screening instrument. Similar nutritional status was found in mild-to-moderate PD patients and matched controls from the same community. Yet, approximately one third of people with mild-tomoderate PD were either malnourished or at risk of malnutrition. Duration of PD, severity of motor symptoms, depression, anxiety and fatigue associated with nutritional status in PD patients. Motor symptoms affecting activities of daily living (ADL), depression, anxiety and female sex were found to be the strongest independent determinants of HRQoL in Iranian PD population. Clear heterogeneities were found in the pattern and determinants of HRQoL in different PD phenotypes, which should be considered during the assessments and developing personalized interventions to improve life quality in PD patients with different prominent features.