Binkolkata.in

Epidemiology of Parkinson disease in the city of Kolkata, India: A
community-based study
S.K. Das, A.K. Misra, B.K. Ray, A. Hazra, M.K. Ghosal, A. Chaudhuri, T. Roy, T.K.
Banerjee and D.K. Raut Neurology 2010;75;1362-1369 DOI: 10.1212/WNL.0b013e3181f735a7 This information is current as of October 15, 2010
The online version of this article, along with updated information and services, is located on the World Wide Web at: Neurology® is the official journal of the American Academy of Neurology. Published continuouslysince 1951, it is now a weekly with 48 issues per year. Copyright 2010 by AAN Enterprises, Inc. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.


Epidemiology of Parkinson disease in thecity of Kolkata, IndiaA community-based study Objective: No well-designed longitudinal study on Parkinson disease (PD) has been conducted in
India. Therefore, we planned to determine the prevalence, incidence, and mortality rates of PD in the city of Kolkata, India, on a stratified random sample through a door-to-door survey.
Method: This study was undertaken between 2003 to 2007 with a validated questionnaire by a
A. Chaudhuri, PhD team consisting of 4 trained field workers in 3 stages. Field workers screened the cases, later confirmed by a specialist doctor. In the third stage, a movement disorders specialist undertook T.K. Banerjee, FRCP home visits and reviewed all surviving cases after 1 year from last screening. Information on death was collected through verbal autopsy. A nested case-control study (1:3) was also under-taken to determine putative risk factors. The rates were age adjusted to the World StandardPopulation.
Address correspondence andreprint requests to Dr. Shyamal Result: A total population of 100,802 was screened. The age-adjusted prevalence rate (PR) and
Kumar Das, Department of average annual incidence rate were 52.85/100,000 and 5.71/100,000 per year, respectively.
Neurology, Bangur Institute ofNeuroscience, Kolkata 700025, The slum population showed significantly decreased PR with age compared with the nonslum population. The adjusted average annual mortality rate was 2.89/100,000 per year. The relative risk of death was 8.98. The case-control study showed that tobacco chewing protected andhypertension increased PD occurrence.
Conclusion: This study documented lower prevalence and incidence of PD as compared with Cauca-
sian and a few Oriental populations. The mortality rates were comparable. The decreased age-
specific PR among slum populations and higher relative risk of death need further probing. Neurology®
2010;75:1362–1369
GLOSSARY
AAIR
⫽ average annual incidence rate; AAMR ⫽ average annual mortality rate; CI ⫽ confidence interval; FSQ ⫽ family
screening questionnaire; ICC ⫽ intraclass correlation coefficient; IR ⫽ incidence rate; MD ⫽ movement disorder; NSSO
National Sample Survey Organization; OR ⫽ odds ratio; PD ⫽ Parkinson disease; PPS ⫽ parkinsonism plus syndrome; PR
prevalence rate; PRM ⫽ Poisson regression modeling; RR ⫽ relative risk; SP ⫽ secondary parkinsonism; VA ⫽ verbal autopsy.
The epidemiology of Parkinson disease (PD) has important public health and social implicationsand also provides etiologic clues. India is a multiethnic country with genetic diversity. Recentcross-sectional studies from India, besides the Parsis study, have shown lower age-adjusted preva-lence rates (PRs) of PD in comparison with predominantly Caucasian and a few Oriental popula-tions (table 1).1-11 In India, with an aging population and increased life expectancy, it is expectedthat the disease burden due to PD will be enormous, but there is no prospective study to estimate itsincidence and mortality. The incidence rates (IRs) in different countries vary from 1.5 to 20 per100,000 per year.12-20 The wide discrepancy in rates among different studies may stem from ethnic-ity, environmental factors, and varied methodology. Previous studies have shown that subjects withParkinsonism have a higher relative risk of death compared with nonparkinsonian subjects in thesame age range.14,21 The low PR in most of the Indian studies may be due to either lower incidenceor higher mortality or a combination of the two.
From the Bangur Institute of Neuroscience (S.K.D., A.K.M., B.K.R., T.R.), Kolkata; Institute of Post-Graduate Medical Education and Research(A.H.), Kolkata; Institute of Psychiatry (M.K.G.), Kolkata; Indian Statistical Institute (A.C.), Kolkata; National Neurosciences Centre (T.K.B.),Kolkata; and All India Institute of Public Health and Hygiene (D.K.R.), Kolkata, India.
Study funding: Supported by the Indian Council of Medical Research (SWG/Neuro/9/2001-NCD-I and SWG/Neuro/20/2005/NCD-I).
Disclosure: The authors report no disclosures.
Copyright Inc.


Frequency of Parkinson disease as reported by studies from India and abroad
Period of
rate (per 100,000)
rate (per 100,000)
102,557 (Rural and urban) Caucasians 87,025 Abbreviations: CLS ⫽ case linkage study; DDS ⫽ door-to-door survey.
a To US 1960 population.
b To US 1990 population.
c To US 2000 population.
d To US 1970 population.
e To Japan 1990 population.
f Standard population not mentioned.
Therefore, we planned to undertake a ered at least 1 year of residency in the area to avoid the float- door-to-door survey on a large heterogeneous ing population.
A validated family screening questionnaire (FSQ) was used population in the metropolitan city of Kolk- to detect cases of major neurologic illnesses. This was adminis- ata, India, to determine the prevalence, inci- tered to the head of the family by field workers.2 In cases of dence, and mortality rates of PD. A nested confused PD patients as determined from history and examina- case-control study was undertaken to deter- tion, spouses or reliable family members were interviewed. Thisquestionnaire also contained information on demography and mine putative risk factors.
questions to detect cases with movement disorders (MDs) in-cluding PD, such as tremulous movement of head, arms, and METHODS A prospective community-based study was con-
legs and speech and gait abnormalities. We added 3 more ques- ducted to find subjects with PD through a 3-stage house-to- tions to capture subjects with MDs.
house survey. The institutional Ethics Committee cleared the Survey. In the first stage, field workers screened the sample for
proposal, and written informed consent was obtained before the positive cases. The field doctor examined them, recorded the clinical details, and verified randomly chosen 10% of screened Sampling. The sampling strategy has been published else-
negative population in each block to detect the false-negative where. The survey area was the municipal limits of the city of cases. The clinical details of all positive cases were scrutinized by Kolkata (erstwhile Calcutta) with an area of 185 km2 and popu- a team of senior neurologists, including MD specialists, and a lation of 4.58 million.3 consensus diagnosis was reached. Few subjects were examined The sample was chosen from the whole city through selec- either in the institute or at home for resolving any confusion. In tion of stratified random National Sample Survey Organization the third stage, 1 MD specialist revisited all houses of the diag- (NSSO, India) blocks based on geographical location and dwell- nosed cases after 1 year of completion of the initial survey for ings. The city population was initially divided into slum- follow up and recorded any change in the clinical and treatment dominant and non–slum-dominant areas. A total of 6 strata (1 profile, including death cases.
from slum areas and 5 from nonslum areas) were formed. The In the initial phase, a study was conducted to determine the slum population constitutes approximately one third of the In- sensitivity and specificity of the screening questionnaire for PD dian urban population. The slum dwellers are socioeconomically in the MD clinic, where the specialist acted as the gold standard.
weaker and live in unhygienic, overcrowded conditions. Each An initial cross-sectional survey was undertaken in 2003 to stratum acted as a sampling frame (figure 1) from which a pro-
2004, and subsequently annual screening was performed be- portionate number of NSSO blocks were selected by using ran- tween 2004 and 2008 to find new cases and follow up with the dom number tables. From each block, 50% of alternating old cases. Verbal autopsy (VA) was performed in death cases.
families were surveyed. For purposes of inclusion, we consid- This is a standard method of interview-based retrospective col- Neurology 75 October 12, 2010



lection of information on death from a reliable family member or of parkinsonism plus syndrome (PPS) and secondary parkinson- close associate in the absence of a routine autopsy.22 All data ism (SP) for diagnosis of PD. PPS was considered per defined from VA cases were verified by the field doctor and subsequently criteria.5 SP included those who had obvious causes leading to by a senior doctor. The VA questionnaire was field tested to features of parkinsonism, such as neuroleptic use in the past 6 determine sensitivity and specificity under the supervision of a months preceding the onset of symptoms, infection, trauma, senior doctor, who acted as the gold standard. The period for stroke, and hydrocephalus.
prevalence was considered up to December 31, 2007, and inci-dence was calculated for the period between 2003 and 2007.
RESULTS The screened population was 100,802
Statistical analysis. PRs are expressed as per 100,000 popula-
individuals from 21,398 families out of 282 ran- tion. Average annual incidence rates (AAIRs) and average annual domly selected blocks. The literacy rate was 83.23%, mortality rates (AAMRs) are expressed as per 100,000 popula- and the sex ratio (men to women) was 1:1.12. A total tion per year. Age-adjusted rates were calculated by adjustment of 89 families refused or could not be contacted for directly to World Standard Population.23 The 95% confidence participation in the study. The total population was intervals (CIs) of all the rates were calculated based on Poissondistribution. The ␹2 test was used to assess significance of differ- exclusive of refusal cases.
ences in unpaired proportions; p ⬍ 0.05 was considered signifi- The screening instrument for capturing PD cases cant. A nested case-control study was undertaken with age (⫾5 showed a sensitivity of 88.23% (lower limit of 95% years)–matched and sex-matched controls to assess the risk fac- CI 63.09) and specificity of 100% (lower limit of tors of PD. Controls were selected randomly from the case 95% CI 71.40) based on 40 clinic cases, and sensitiv- neighborhood in a 1:3 (case-to-control) ratio, and 92% agreed to ity and specificity of VA were 97.5% and 57.14% participate (table e-1 on the Neurology® Web site at www.
neurology.org). Multivariate analysis of the case-control data was based on 61 randomly selected community death performed through conditional logistic regression. Poisson re- gression modeling (PRM) was applied on prevalence and IR data The intrarater validation of individual questions to assess their relation with age and sex. Kaplan-Meier survival on the FSQ showed perfect agreement among the 3 analysis was conducted with the prevalent cases of PD, the sur- raters for all except 2 questions, which had an intra- viving cases being censored at the time of study closure. Statistica class correlation coefficient (ICC) value of 0.794, in- versions 6 [StatSoft Inc., Tulsa, OK; 2001] and 17 [SPSS Inc.,Chicago, IL; 2008] were used for statistical analysis.
dicating strong agreement. In interrater validation,there was perfect agreement between raters in all but Operational definition. To minimize the number of cases
3 questions. For 2 of these questions, agreement was missed, the presence of at least 2 of the following features wasconsidered for parkinsonism: rest tremor, bradykinesia, rigidity, strong (ICC 0.794), and for 1, it was fair (ICC and postural instability.24 We excluded those cases with features 0.310) (details in table e-2).


Prevalence, incidence, mortality rates of Parkinson disease in Kolkata, India, and the corresponding
age-adjusted and sex-specific ratesa

Crude rate
M: 45.15 关26.77–71.38兴,F: 60.34 关37.95–91.15兴 4.56 关2.87–7.51兴 5.71 关3.59–9.40兴 M: 5.01 关2.50–8.96兴, F: 6.20 关3.21–10.84兴 2.28 关1.21–3.80兴 2.89 关1.54–4.94兴 M: 2.65 关1.14–5.22兴, F: 1.89 关0.60–4.34兴 a Figures in brackets denote corresponding 95% confidence intervals.
b Age-adjusted rate to Worlds Standard Population.
Table 2 shows the PR, AAIR, and AAMR of PD.
in table 4. PRM analysis of these results showed IR Tables 3 and 4 depict age and sex distribution of the increasing with age ( p ⬍ 0.001), but sex had no ef- sample, which matched with the city population fect ( p ⫽ 0.052).
(Census India, 2001).
Follow-up and mortality. In the third stage
Prevalence. Of 52 cases with parkinsonism, PD was
(follow-up visit), there were 13 deaths (8 men, 5 detected in 41 cases (the rest were PPS [6] or SP [5]).
women) of 41 cases over a period of 6 years, and a Table 3 shows overall, age- and sex-specific, and age- total of 3 cases could not be examined because of adjusted PRs. By applying PRM, the PR rate showed refusal (1) and migration (2). Of the remaining 25 a significant, but nonlinear increase with age ( p ⬍ cases, 1 case had multiple system atrophy, and an- 0.001) in comparison with sex ( p ⫽ 0.01). The mean other had features of essential tremor. Thirteen sub- age of the subjects was 62.03 years (range 28 – 82 jects were taking levodopa preparation and 9 other years). Prior diagnosis was made in 23 cases anticholinergics. Most of the subjects had shown a (56.09%), and only 18 cases (43.90%) received therapeutic response. None showed dyskinesia, treatment. By applying PRM, the PR of the nonslum but they received relatively low doses of levodopa.
population showed a significant increasing rate with Additionally, 3 subjects were taking antipsychotics, 3 advancing age above 62.5 years compared with the were taking antidepressants, and 4 were taking anti- slum population.
hypertensives for comorbid disorders.
Incidence. A total of 23 cases of PD had onset of
Overall AAMR and sex-specific mortality are pro- illness over the 5-year study period, and the AAIRs, vided in table 2. The difference of AAMR between age-adjusted rates, and sex-specific IRs are provided slum (2.02) and nonslum (2.39) populations was in- Age- and sex-specific prevalence of Parkinson disease in Kolkata, India
Age band, y
Total (95% CI)
33.83 (20.06–53.49) 46.23 (30.40–70.30) 40.67 (29.04–55.40) AAR (95% CI)
45.15 (26.59–70.91) 60.34 (37.95–91.15) 52.85 (37.74–71.98) Abbreviations: AAR ⫽ age-adjusted rate; CI ⫽ confidence interval; PR ⫽ prevalence rate.
Neurology 75 October 12, 2010


Age- and sex-specific incidence of Parkinson disease in Kolkata, India
Population cases AAIR
Population cases AAIR
Population cases AAIR
4.13 (2.06–7.39) 47,593 5.04 (2.61–8.80) 4.56 (2.87–7.51) 5.01 (2.50–8.96) 6.21 (3.21–10.49) 5.71 (3.59–9.40) Abbreviations: AAIR ⫽ average annual incidence rate; AAR ⫽ age-adjusted rate (to World Standard Population); CI ⫽ confi-dence interval.
significant. Maximum mortality was observed in the predictability was modest, with a Nagelkerke R2 70- to 74-year age band. The mean age of death cases value at 0.137.
was 71.31 years (men: 70.38, women: 72.8). Thestandardized mortality ratio was 3.79 (95% CI 2.01– DISCUSSION One concern about diagnosis of PD is
6.48; men: 5.23, women: 2.53). Thirteen cases of 31 the lack of biomarkers and dependence on clinical evi- with PD and age greater than 55 years died, and over dence. Epidemiologic ascertainment of cases is com- the same period, 590 subjects of 12,683 nonparkin- monly based on the administration of interview-based sonian population died of other causes. So the rela- questionnaires. Sensitivity and specificity of such ques- tive risk (RR) stood at 8.98 (95% CI 5.89 –13.70).
tionnaires depends on the number of questions, and The most probable causes of death were prolonged various studies have shown that a minimum number of bedridden state in 3 (23.07%), ischemic heart disease questions (as low as 2) improves sensitivity but decreases in 3 (23.07%), cerebrovascular accident in 2 specificity.25 Conversely, by increasing the number of (15.38%), asthma in 2 (15.38%), train accident in 1 questions, specificity may be increased, but sensitivity is (7.6%), sunstroke in 1 (7.6%), and cancer in 1 reduced. However, the lower limit of sensitivity and (7.6%). The median survival time based on Kaplan- specificity of the PD screening instrument indicates that Meier survival analysis was 13.5 years (figure e-1).
a few cases might have been misdiagnosed or early cases Case-control analysis. Both univariate and multivari-
might have been missed.
ate analysis were conducted to detect the association The adjusted PR of PD in this study and those of of risk factors of PD. Among controls, the preva- other recently conducted studies from India1-3 have lences of smoking and tobacco chewing were 33.3% documented lower values as compared with Cauca- and 26.08% among men and 0% and 20.37% sian populations. A lower prevalence of PD has been among women. In univariate analysis, history of reg- shown among Bulgarian gypsies of presumably In- ular tobacco use (besides smoking) showed a lower dian origin in comparison with Caucasians living in risk for development of PD (odds ratio [OR] 0.15, the same environment.6 Similarly, an Anglo-Indian 95% CI 0.04 – 0.70), whereas hypertension increased study from Southern India recorded a very low prev- the risk (OR 2.45, 95% CI 1.03–5.84). The other alence of PD.26 These 2 studies suggest a possible role putative risk factors did not show appreciable in- of genetic influence. Only the study among Parsis crease or decrease in odds. In conditional logistic re- from India observed high prevalence of PD, which gression analysis, only nonsmoking tobacco use can be explained by a distinct ethnicity and higher showed up as a significant factor decreasing risk (ad- aging population.13 Hence, lower prevalence among justed OR 0.16, 95% CI 0.03– 0.75). The overall Indian studies may be true and may be related to


either low incidence or increased mortality. The tobacco chewing, similar to another report from In- higher prevalence of PD among women has been dia.32 The effect of tobacco chewing is prolonged be- documented in Finland, Japan, and India.1,27,28 This cause of persistent contact with buccal mucosa and may be related to environmental factors rather than provides higher potency than smoking cigarettes.33 genetic factors. Lack of estrogenic support was shown The role of vascular pathology and that of hyperten- to induce nigral cellular degeneration in animals.29 sion have been emphasized in vascular parkinson- Because tobacco smoking was infrequent among ism.34 However, hypertension is now considered as a women in this study, the prevalence of PD may be risk factor in neurodegenerative disorders such as higher because of lack of its protective effect.30 How- Alzheimer disease.35 Therefore, it is possible that hy- ever, the lack of simultaneous increase of PR of PD pertension may accelerate neurodegeneration. Con- among the slum population compared with the non- versely, a few cases of vascular parkinsonism also slum population might indicate a protective effect respond to levodopa.36 It is noteworthy that the inci- due to some environmental factor, which needs to be dences of hypertension and stroke are increasing in probed further.
India,37 and some of the PD cases may be truly vascu- This study documented a lower AAIR of PD as lar in origin and probably misdiagnosed because of compared with North American (20),14 many Euro- levodopa responsiveness and lack of biomarkers em- pean (19),15,16 Japanese (15),10 Australian (7),18 and phasizing further study.
Chinese in Taiwan (10)9 populations, but similar to 1 Therefore, the lower prevalence of PD is explainable Italian (10)16 and Libyan population (4.5)18 and higher by lower IR, which may be related to either genetic or than in the Chinese population (1.5).8 Age-specific environmental factors. The studies from India have AAIRs were also lower in comparison with similar stud- documented a genetic contribution in up to 8.5% of ies in the above populations.9,10,13–18 A meta-analysis by cases of familial and sporadic PD.38 Thus, in the ab- Zhang et al. showed that there was no change in IRs sence of a genetic contribution, environmental factors over the past 50 years, signifying that adjusted IR in this may confer protection. Various phenolic compounds, study is possibly stable.12 This study has shown no sig- such as curcumin from turmeric, have shown antioxida- nificant difference in sex-specific incidence and, hence, tive and anti-inflammatory effects.39 Interestingly, Indi- suggests that the chance of developing PD is almost ans consume curcumin daily in their diet from equal in both sexes. Conversely, evidence of 2-fold early childhood. Curcumin prevents aggregation of higher incidence among Italian men over women may ␣-synuclein in experimental animals and possibly cell indicate a probable influence of sex in the occurrence of death.40 It is possible that long-term consumption of PD.31 The role of ethnic influence is revealed from dif- curcumin might confer protection against development ferent IRs among different racial populations, and the of PD. This issue merits exploration.
lowest rate is noted among Asians.32 This is in accor- There are some limitations in this study. Because dance with our finding.
The AAMR of this study is comparable with those the method of case ascertainment is interview based, of studies worldwide, varying between 0.5 and 3.8 per early cases may be missed. The lower 95% confi- 100,000.27 The higher mortality rate among men can dence limit of sensitivity and specificity of the screen- explain the higher prevalence among women. However, ing instrument might indicate that a few early cases the median survival time in this study is close to that of may have been missed. Thus, the estimate could be Taiwan.9 The causes of death in this study differ from higher. Many elderly persons could not tell the exact another Asian study where pneumonia was a com- date of birth, and so lack of uniformity of age- monly recognized cause of death among patients with specific IRs and PRs may be related to misgrouping PD. Also, a higher RR as compared with the United of the subjects in different age bands. The diagnosis States (2.2)21 and Taiwan (3.8)9 and standardized mor- of PD is clinical, and some of the PD cases might be tality ratio in this study (8.98) indicate either more se- variants of PPS, if autopsy could be performed in vere disease or a deficiency of health care in the death cases. The case-control study has limitations, community.8 Lack of a social support system and pau- such as recall bias and improper quantification of the city of trained manpower, rather than socioeconomic exposure of interest. The specificity of VA is usually factors, are the main constraints, because there was no low because there is no way to validate the diagnosis significant difference in mortality between slum and in the absence of autopsy verification.22 nonslum cases. The earlier age at death is possibly a Nevertheless, we have documented lower PRs and reflection of the general pattern of mortality in individ- IRs of PD. Mortality is comparable. In view of the close ual countries, depending on life expectancy.
age and sex matching of our sample to the Kolkata pop- The case-control study revealed that the only risk ulation, the results are generalizable. The case-control factor was hypertension and a protective factor was study shows that PD increases with systemic hyperten- Neurology 75 October 12, 2010


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"An enlightening guide. . this patient-oriented approach should be hailed as a groundbreakingbook. It is highly recommended for any patients suffering from these often undiagnosed and un-treated disorders and the relatives who help care for them."—Alan R. Hirsch, MD, neurological director at the Smell and Taste Treatment and ResearchFoundation in Chicago Invite your patients to visit www.aan.com/view/smellandtaste for more information about this invalu-able resource. Available from all major booksellers.
Neurology 75 October 12, 2010 Epidemiology of Parkinson disease in the city of Kolkata, India: A
community-based study
S.K. Das, A.K. Misra, B.K. Ray, A. Hazra, M.K. Ghosal, A. Chaudhuri, T. Roy, T.K.
Banerjee and D.K. Raut Neurology 2010;75;1362-1369 DOI: 10.1212/WNL.0b013e3181f735a7 This information is current as of October 15, 2010
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This article, along with others on similar topics, appears in the
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Parkinson's disease/Parkinsonism
http://www.neurology.org/cgi/collection/parkinsons_disease_parki
Prevalence studies
Risk factors in epidemiology
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Painkillers can bring relief to people who are suffering from pain when taken as directed. However, the dangers of misuse must also be highlighted. Many painkillers are available over-the- effects such as drowsiness. This is why it counter (OTC) from pharmacies and is so important to read the information A huge market exists for painkillers and it shops without the need for a

S108-02

Victoria Government Gazette No. S 108 Tuesday 25 June 2002 By Authority. Victorian Government Printer Transport Act 1983 ORDER AS TO DECLARED DRUGS I, Peter Batchelor, acting under section 93(1AA) of the Transport Act 1983, by this each of the substances specified in the Schedule to this Order; and (ii) any natural principle, any natural or