Introduction

Parkinson’s Disease represents the second neurodegenerative disorder in the world after Alzheimer’s disease with an estimated prevalence of 3% in the elderly and overal 0.3% of population is affected [1-3]. This condition, is caused by degeneration of the dopaminergic neurons of the substantia nigra in the midbrain, is associated with motor symptoms like bradykinesia, rest tremor, rigidity and postural instability and various non motor sympyoms [4]. The hallmark is bradykinesia, leading to slow gait, difficulty standing from sitting, small stride length, reduced arm swing, rigidity in trunk movements, propulsion and retropulsion [5]. Non- motor symptoms (NMSs) include neuropsychiatric features (anxiety, depression, apathy, hallucinosis/ psychosis) sleep disturbance and hypersomnolence, fatigue, pain, sphincter disturbance and constipation, sexual problems (erectile failure, loss of libido or hypersexality), drooling and weight loss [6-8]. Cognitive impairment, including dementia is the symptom most likely to impair quality of life for patients and their carers. These symptoms constitute a burden on the caregiver and the public health system. In the PRIAMO study, up to 98.6% of PD patients had NMS. Recently, the correlation between NMS and PD patients’ health-related quality of life (HRQoL) has been emphasized [9]. Several studies indicate that NMS, rather than motor symptoms, are a major cause of poor health related quality of life (HRQoL) [10,11]. Recently, two complementary instruments to assess non-motor symptoms in PD have been developed: The Non Motor Symptoms Questionnaire (NMS Quest) and the Non motor Symptoms Scale (NMSS) [12,13]. The NMS screening questionnaire (NMS Quest), a self-completed questionnaire comprising 30 items, used as rapid screening tool, for the early detection of patient’s non-motor symptoms (NMSs) [14,15]. Also NMSs is used for NMS burden assessment. Several studies have compared non-motor symptoms (NMS) in different countries and showed more prevalent gastrointestinal symptoms in Asian countries, probably due to ethnic and economic differences [16,17]. NMS have a deep impact on PD patients’ quality of life [14]. The purpose of my study is to investigate NMS in PD patients attending in Neurology department BMU and the impact of NMS on HRQOL. This hospital-based cross-sectional study was conducted to examine the clinical factors, on the occurrence of non-motor symptoms (NMSs) and health related quality of life (HRQOL). 30-item Parkinson’s Disease Questionnaire (PDQ-30) and Validated Bengali version of WHOQOL- BREF were usedto explore the correlation [17].

Methodology & Materials

This cross-sectional study was conducted in the movement disorder clinic, out patient and in patient department of Bangladesh Medical University (BMU), Dhaka over a period one year from October 2019 to September 2020. A total of 76 patients diagnosed as idiopathic Parkinson's disease with Non Motor symptoms was taken as study population. Patients with anti psychotic drug induced NMSs, secondary cause of parkinsonism, those who will not provide consent and atypical parkinson’s disease were excluded from the study. Approval from the Institutional Review Board (IRB) of BMU was obtained prior to the commencement of this study. Idiopathic Parkinson’s Disease patients was diagnosed on brain bank criteria. Parkinson’s disease of patient was selected from movement disorder clinic, outpatient and inpatient Department of Neurology of BMU. After taking proper history, physical and neurological examination and relevant investigations were done. Informed written consent was taken from each patient. After diagnosis of idiopathic Parkinson’s disease detected by non-motor symptoms assessment scale (developed by the international Parkinson’s disease non- motor group) Quality of life in idiopathic Parkinson’s disease detected by who quality of life scale. Proper diagnosis and treatment was ensured for each patient. Collected data were compiled and appropriate analyses were done by using computer based software, Statistical Package for Social Sciences (SPSS) version 23.0. Qualitative variables were expressed as percentage and quantitative variables as median or mean. Pearson’s correlation coefficient was calculated between Hoehn and Yahr stage with total Score Domain and also Pearson’s correlation coefficient was calculated between Diseases duration vs Nonmotor Symptom Domain 1 to Domain 6. A ‘p’ value of <0.05 was considered as significant.

Result

Out of 76 patients, among the patients highest (27.6%) were in the age group between 61 to 70 years of age and the lowest (2.6%) were in the age group of 81 to 90 years. The age mean and standard deviation (±SD) of the patients were 3.25 ±1.45 years. Among the patients most of them (72.4%) were male and the rest of (27.6%) were female. Among the 76

Table 1: Distribution of the patients by baseline charactreristics.

Table 2: Domain 1: Cardiovascular including falls (score) and

Domain 2: Sleep/fatigues

patients most of them (64.5%) treatment duration was between 1 to 4 years and the lowest (5.3%) diseases duration were bellow one year (Table-1). Among the patients score highest(42.11%) Hoehn and Yahr stage (score) were 2 followed by(39.37%) were 1 and lowest (3.94%) were 0 (Figure-1). In domain 1 among the patients score highest (68.4%) dizziness score was >1 and highest (93.4%) fall score were zero (0). In domain 2 among the patients score highest (73.7%) daytime sleep score was zero (0) and highest (75%) Difficulties fall and staying sleep score were >1 and highest (59.2%) were restless in legs score were zero (0). The following table 11 shows in details (Table-2). In domain 3 among the patients score highest (59.2%) lots of interest in his/her surroundings score were zero (0) and highest (65.8%) Lost of interest in new activities score were >1 and highest (77.7%) feeling of nervous score were >1 and highest (62.4%) depressed mood score was >1 and highest (61.8%) flat mode score was >1 and highest (59.2%) lack of pleasure score were >1 (Table-3). In domain 4 among the patients score highest (90.8%) see the things are not there/hallucination score were zero (0) and highest (92.1%) belief that you are not real/delusions score were zero (0) and highest (88.2%) double vision score was zero (0). In domain 5 among the patients score highest (50%) Problem of concentration driving activities score were zero (0) and highest (59.2%) Short term memory lost score were >1

(Table-4). Positve significant correlation (r=0.409; p=0.001) was found between Hoehn and Yahr stage (score) and Total Score Domain 1 to Domain 9 (Table-5). Positve significant correlation was found between diseases duration of the patients and Domain 2: Sleep/fatigues (r=0.227; p=0.049). Positve significant correlation was found between Domain 1: Cardiovascular including falls and Domain 2: Sleep/fatigues (r=0.257; p=0.025) and Domain3: Mood/cognition (r=0.328; p=0.004) (Table-6). Positve significant correltion was found between diseases duration of the patients and Domain 5: Attention/memory (r=0.315; p=0.006) and Domain 6: Gastrointestinal tract (r=0.316; p=0.005). Positve significant correltion was found between Domain 4: Perceptual problem and Domain 5: Attention/memory (r=0.225; p=0.026). Positve significant correltion was found between Domain 5: Attention/memory and Domain 6: Gastrointestinal tract (r=0.352; p=0.002) (Table-7).

Figure 1: Hoehn and Yahr stage (score)

Table 3: Domain 3: Mood/cognition.

Table 4: Domain 4: Perceptual problem & Domain 5: Attention/

memory.

Table 5: Hoehn and Yahr stage with total Score Domain.

Table 6: Diseases duration vs Nonmotor Symptom Domain 1 to Domain 3 Correlations.

Table 7: Diseases duration vs Nonmotor Symptom Domain 4 to Domain 6 Correlations.

Discussion

Parkinsons Disease affect about 1-2% of the population over 65 years of age & upto 3-5% of people 85 years of age & older [18]. The results show a high prevalence of NMSs in our patients, in whom at least one NMS has been found. The results are NMSs prevalence rate of 100%. Other study NMSs of Parkinsons disease and impact on quality of life in Moroccanpeatients alsoprevalence rate of 100% [19,20]. The total patients of study were 76 whereas male were 55(72.4%) and female were 21 (27.6%). In another study conducted in Thailand, there was 76% respondent was male and rest of them are female. The age of the patients was above 50 years (>64.5%) and below 50 years (35.5%). This finding is similar to the study finding of Li et al. [19]. Among the 76 patients most of them (64.5%) treatment duration was between 1 to 4 years and the lowest (5.3%) disease duration below one year. Longer disease duration, advanced disease, longer levodopa use and higher daily dose are associated with the higher occurrence of non-motor symptoms of PD [9,21,22]. This study’s Hoehn and Yahr stage 2 to 3 is 56.58% and stage 1 is 39.37%. Previous study showed the predominant population in stage 2 to 3 [23]. In this study the most frequent NMSs were dizziness, mood or cognition impairment, difficulties falling and staing sleep and feels of pain. The urinary disturbances were most frequent NMSs in previous studies [10]. But other study sleep and mood/cognition disorder were found in 88.3% and 80.6% of the patients, constituting the non-motor symptoms with the greatest impact on quality of life [24]. In domain 1 among the patients score highest (68.4%) dizziness score and lowest score 6.6% were fall. Almost similar symptoms of dizziness were present in more than half of patients [25]. In domain 2 were difficulties falling and staing sleep up to 75% and day time sleep up to 26.3% participant. Where sleep disorder more frequent NMSs upto 90% of people with PD [26,27]. This study was restless in legs upto 40.8%. Previous studies 8 to 20 % participants were RLS [28]. In domain 3 among the patients were cognition/mood more markly effect such as feeling of nervousness 77.7%, loss of interest in new activities 65.8%, depressed mood 62.4%, flat mode 61.8 % lack of pleasure 59.2% and lost of interest in his/her surroundings 40.8%. Cognitive dysfuntion affects 24% of patients with newly diagnosed PD [29]. Other previous studies 44.7-54% was cognitive impairment [9,22]. However, 63% of our patients admitted having cognitive problems only at slight or mild level. The correlation between cognitive impairment and QoL in patients with PD has been well-established [30,31]. In domain 4 among the patients’ perceptual problem/ hallucination were upto 9%. But previous study was upto one third patients suffer from hallucination chronically treatment PD patients [32]. In domain 5 among the patients were forgetfulness upto 59.2% and loss of concentration 50%. Another study also found that participants with attentional/ memory deficits reported increased PD-39 scores [9]. In this study in domain 6 were constipation 38.2%, difficulty in shallow 19.7% and dribbling of saliva 11.8%. In a previous study constipation was most common symptom and swallowing difficulties were around 20% [9,14]. In domain 7 among the patients were urinary frequency 44.7%, urgency 43.4% and nocturia 34.2%. The most frequent NMSs were the urinary disturbances, which is in line with several previous studies [10]. In domain 8 among the patients were altered interest in sex 48.5% and problem having sex 27.6%. We trivialize the existing troubles and relate them to their advanced age. In a previous study reported that the question relating to sex were frequently left unanswered [14]. In domain 9 among the patients were pain 56.6%, smell disturbance 45.7%, excessive sweating (not related to hoy weather)18.4% and change in weight (not related to dieting) 15.8%. Previous study was pain affects upto 74% of PD patients and due to its heterogenous aetiology, presents a complex diagnostic and management issue.33 Regarding olfactory disorders, they exist in a large majority of PD patients (up to 90%) and most often are present at the time of diagnosis. Overal the relative NMSs occurrence, as evaluated by NMS-30 is consistent dizziness (68.4%), mood/ cognition (67%), difficulties falling sleep (75%), restless in leg (40.8%) and urinary symptoms 40%. Though, in more than 70% of cases, patients are unware of their smell changes. Previous study there is a paucity of work examining the impact of sweating on QoL in PD despite studies showing that it affects almost half of the patients [34]. In this study there was pearson correlation between Hoehn and Yahr symptoms with non-motor symptoms domains 1 to 9. Most of the correlation were significant (<0.05). NMSs have considerable correlation with PDQ-39 scores with p value being significant like that observed in study with p value of (0.000) [10,35]. This study’s disease duration vs non-motor symptom were pearson correlation and most of domain were significant (<0.05). Retrospective study with a long mean duration from PD diagnosis of 7.6±5.6 years, reported 98.9% of subjects experienced prodromal symptoms preceding a diagnosis of PD similar [36]. Hoehn and Yahr stage vs QoL were pearson correlation also significant (<0.05). The Hoehn and Yahr stage correlated more strongly with QoL scores than the motor part of the UPDRS [37]. Identifying the specific patterns of NMSs occurrence concerning time of symptoms has been pivotal in understanding the evoluation and its contribution to disease morbidity of PD individuals. Routine assessment of NMSs by using simple Questionnaires like NMSs quest and their impact on life by using PDQ-30, PDQ-39, PDQ-8 and Hoehn and Yahr scoring [23].

Limitations of the study: Several limitations exist to the present study, the sample size was small (worth to mention the COVID-19 situation which severely hampered sample collection), tt was single centered, study period was short, no further follow up was done, comorbid neurologic disorder were not assessed, motor symptoms also hamper the quality of life and control group was no concideration.

Conclusion

In this study we obseserved significant association of non–motor symptom with QoL NMSs are common in patients with PD, although they are often overlooked. NMSs result in a significant burden for people with PD and negatively affect QoL. Further studies are needed to assess the effect of treating NMSs on improving QoL.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the Institutional Ethics Committee.

References

1. De Lau LM, Breteler MM. Epidemiology of Parkinson's disease. The Lancet Neurology 5 (2006): 525-535.
2. Rodrigues de Paula F, Teixeira-Salmela LF, Coelho de Morais Faria CD, et al. Impact of an exercise program on physical, emotional, and social aspects of quality of life of individuals with Parkinson's disease. Movement disorders: official journal of the Movement Disorder Society 21 (2006): 1073-1077.
3. Souza RG, Borges V, Silva SM, et Quality of life scale in Parkinson's disease PDQ-39-(Brazilian Portuguese version) to assess patients with and without levodopa motor fluctuation. Arquivos de neuro-psiquiatria 65 (2007): 787-791.
4. National Collaborating Centre for Chronic Conditions (Great Britain). Parkinson's disease: national clinical guideline for diagnosis and management in primary and secondary care. Royal College of Physiciansm (2006).
5. Murray MP, Sepic SB, Gardner GM, et al. Walking patterns of men with parkinsonism. Am J Phys Med 57 (1978): 278-294.
6. Haehner A, Hummel T, Hummel C, et al. Olfactory loss may be a first sign of idiopathic Parkinson's disease. Movement disorders 22 (2007): 839-842.
7. Ziemssen T, Reichmann H. Non-motor dysfunction in Parkinson's Parkinsonism & related disorders 13 (2007): 323-332.
8. Chaudhuri KR, Schapira AH. Non-motor symptoms of Parkinson's disease: dopaminergic pathophysiology and treatment. The Lancet Neurology 8 (2009): 464-474.
9. Barone P, Antonini A, Colosimo C, et al. The PRIAMO study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease. Movement disorders: official journal of the Movement Disorder Society 24 (2009): 1641-1649.
10. Martinez-Martin P, Rodriguez-Blazquez C, Kurtis MM, Chaudhuri KR, NMSS Validation Group. The impact of non-motor symptoms on health-related quality of life of patients with Parkinson's disease. Movement Disorders 26 (2011): 399-406.
11. Valkovic P, Harsany J, Hanakova M, et al. Nonmotor symptoms in early-and advanced-stage Parkinson’s disease patients on dopaminergic therapy: how do they correlate with quality of life? International Scholarly Research Notices (2014).
12. Chaudhuri KR, Martinez-Martin P, Brown RG, Sethi K, Stocchi F, Odin P, Ondo W, Abe K, MacPhee G, MacMahon D, Barone The metric properties of a novel non-motor symptoms scale for Parkinson's disease: results from an international pilot study. Movement disorders 22 (2007): 1901-1911.
13. Martinez-Martin P, Rodriguez-Blazquez C, Abe K, et al. International study on the psychometric attributes of the non-motor symptoms scale in Parkinson disease. Neurology 73 (2009): 1584-1591.
14. Chaudhuri KR, Healy DG, Schapira AH. Non-motor symptoms of Parkinson's disease: diagnosis and management. The Lancet Neurology 5 (2006): 235-45.
15. Sauerbier A, Jitkritsadakul O, Bhidayasiri R, et al: Non- motor symptoms profilesof different ethnic groups with Parkinson’s disease: a cross sectional study comparingthe UK, Thailand, Nigeria and Kuwait. Mov Disord 30 (2015): 2097.
16. Azmin S, Khairul Anuar AM, Tan HJ, et al. Nonmotor symptoms in a Malaysian Parkinson’s disease Parkinson’s Disease (2014).
17. Tsuboi Y, Yamada T, Chaudhuri RK, et al. Comparison of profile of non motor symptoms in Japanese patients with PD with European patients and healthy controls. Extension of the NMSQuest study.
18. Alves G, Forsaa EB, Pedersen KF, et al. Epidemiology of Parkinson’s disease. Journal of neurology 255 (2008): 18-32.
19. Li H, Zhang M, Chen L, Zhang J, Pei Z, Hu A, Wang
20. Nonmotor symptoms are independently associated with impaired health-related quality of life in Chinese patients with Parkinson's disease. Movement Disorders. 2010;25(16):2740-6.
21. Bugalho P, Lampreia T, Miguel R, et al. Non-Motor symptoms in Portuguese Parkinson’s Disease patients: correlation and impact on Quality of Life and Activities of Daily Living. Scientific reports 6 (2016): 32267.
22. Krishnan S, Sarma G, Sarma S, et al. Do nonmotor symptoms in Parkinson's disease differ from normal aging? Movement Disorders 26 (2011): 2110-2113.
23. Spica V, Pekmezovic T, Svetel M, et al. Prevalence of non-motor symptoms in young-onset versus late-onset Parkinson’s disease. Journal of Neurology 260 (2013): 131-137.
24. Karri M, Ramasamy B, Kalidoss Prevalence of non- motor symptoms in Parkinson's disease and its impact on quality of life in tertiary care center in India. Annals of Indian Academy of Neurology 23 (2020): 270.
25. Berganzo K, Tijero B, González-Eizaguirre A, et al. Motor and non-motor symptoms of Parkinson's disease and their impact on quality of life and on different clinical subgroups. Neurología (English Edition) 31 (2016): 585-591.
26. Tomic S, Rajkovaca I, Pekic V, et Impact of autonomic dysfunctions on the quality of life in Parkinson’s disease patients. Acta Neurologica Belgica 117 (2017):207-211.
27. Caap-Ahlgren M, Dehlin O. Insomnia and depressive symptoms in patients with Parkinson's disease: relationship to health-related quality of An interview study of patients living at home. Archives of gerontology and geriatrics 32 (2001): 23-33.
28. Olson EJ, Boeve BF, Silber MH. Rapid eye movement sleep behaviour disorder: demographic, clinical and laboratory findings in 93 cases. Brain 123 (2000): 331-339.
29. Gómez-Esteban JC, Zarranz JJ, Tijero B, et al. Restless legs syndrome in Parkinson's disease. Movement Disorders 22 (2007): 1912-1916.
30. Muslimovic D, Post B, Speelman JD, Schmand B. Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology 65 (2005): 1239-1245.
31. Kuopio AM, Marttila RJ, Helenius H, et The quality of life in Parkinson's disease. Movement disorders: official journal of the Movement Disorder Society 15 (2000): 216-223.
32. Greene T, Camicioli R. Depressive symptoms and cognitive status affect health-related quality of life in older patients with Parkinson's disease. Journal of the American Geriatrics Society 55 (2007): 1888-1890.
33. Papapetropoulos S, Mash DC. Psychotic symptoms in Parkinson’s disease. From description to etiology. J Neurol. 2005;252(7):753-64.
34. Roh JH, Kim BJ, Jang JH, et al. The relationship of pain and health-related quality of life in Korean patients with Parkinson’s Acta Neurologica Scandinavica. 119 (2009): 397-403.
35. Magerkurth C, Schnitzer R, Braune S. Symptoms of autonomic failure in Parkinson’s disease: prevalence and impact on daily life. Clinical Autonomic Research 15 (2005): 76-82.
36. De Souza A, Pai Kakode VR, D Costa Z, et Non-motor symptoms in Indian patients with Parkinson’s disease, Basal Ganglia 5 (2015): 89-93.
37. Walter U, Kleinschmidt S, Rimmele F, et al. Potential impact of self-perceived prodromal symptoms on the early diagnosis of Parkinson’s disease. Journal of neurology 260 (2013): 3077-3085.
38. Jiang JL, Tsai ST, Hsieh TC, et al. The impact of motor and depressive symptoms on quality of life in patients with Parkinson's disease. Tzu Chi Medical Journal 25 (2013).