Abstract
Background:
There is a lack of studies of Parkinson’s disease (PD) in immigrants.
Objective:
To study the association between country of birth and incident PD in immigrants in Sweden versus Swedish-born individuals.
Methods:
Study population included all adults aged 50 years and older in Sweden (n = 2775736). PD was defined as having at least one registered diagnosis of PD in the National Patient Register. The incidence of PD in different first-generation immigrant groups versus Swedish-born individuals was assessed by Cox regression, expressed as hazard ratios (HRs) and 95% confidence intervals (CI). The models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, neighbourhood socioeconomic status and co-morbidity.
Results:
Totally 35833 individuals had an incident diagnosis of PD (20401 men and 15432 women). Incidence rates per 100,000 person-years were for all Swedish-born 95.9 and for all foreign-born 60.1; for all men 112.3 and for all women 73.4, with a male to female ratio of 1.53, with the highest incidence rates for the group 80–84 years of age. After adjusting for potential confounders, the overall relative risk of PD was lower in immigrant men (HR 0.78; 95% CI 0.74–0.82) and women (HR 0.92; 95% CI 0.87–0.98). Among immigrant subgroups, a higher risk of PD was found among women from Finland (HR 1.13; 95% CI 1.05–1.23).
Conclusion:
In general, the risk of PD was lower in first-generation immigrant men and women compared to Swedish-born. The only group with a higher risk of PD was women from Finland.
INTRODUCTION
Parkinson’s disease (PD) is a progressive neurodegenerative condition affecting 94/100,000 of the worldwide population (112/100,000 in men and 80/100,000 in women, male to female ratio 1.40), mostly in the ages 50 years and above [1]. The prevalence between 1990 and 2016 has increased by 145% in absolute number of individuals with PD, and by 22% in age-standardized prevalence estimates [1]. PD appears in familial and sporadic cases, and even if the etiology of the disease is largely unknown, PD is likely to be multi factorial with both genetic and environmental factors being important in the pathogenesis [2]. PD varies by age, gender and ethnicity, with higher incidence among elderly, men and individuals of Caucasian origin [3]. Furthermore, environmental factors have been associated with PD, including socio-economic factors [4], occupational exposures, cigarette smoking, dietary factors, and exposure to pesticides [2, 3].
In Sweden, the annual age-adjusted incidence of PD is estimated at 22.5/100,000 (with male to female ratio 1.2), with a cumulative incidence up to 89 years of age for men of 3.4%, for women 2.6% (male to female ratio 1.3), and for both sexes combined 2.9% [5].
In Sweden, foreign-born individuals account for approximately 17% of the registered Swedish population [6]. The prevalence of PD in immigrants in Europe was estimated in a recently published study [7]. A Danish study found a high risk of individuals from the Faroe Islands, which, however, shows a higher PD prevalence than surrounding countries [8]. The topic of atypical parkinsonism in Afro-Caribbean and Indian Origin Immigrants especially to the UK has been debated [9], and is also described in Caribbean populations [10, 11], possible due to consumption of soursop (Annona muricata).With the exception of the study mentioned above [7], no specific study on PD in immigrants in Sweden, a country with universal health care and a high proportion of immigrants, have been performed.
The aim of the present study was to analyse the incidence of PD among first-generation immigrants in Sweden compared to individuals of Swedish origin.
METHODS
Design
The registers used in the present study were the Total Population Register and the National Patient Register (NPR). Subjects aged 50years of age and older were included in the study. The follow-up period ran from January 1, 1998 until hospitalisation/out-patient treatment of PD at age of diagnosis of 50 years or more, death, emigration or the end of the study period on December 31, 2012, whichever came first. Out-patient diagnoses were included nationwide from 2001 and onwards from specialist care, not primary health care. We included only first-generation immigrants, as the number of second-generation immigrants diagnosed with PD were too few.
Outcome variable
PD(G20).
Co-morbidities
We identified co-morbidities of possible importance according to ICD-10 for the following diagnoses: diabetes (E10–E14), hypertension (I10–I19), stroke (I60–69), depression (F32–F34, and F38–F39), anxiety (F40–41), dementia (F00, F01, F02, F03, G30, and G31.8A), sleep disorders (G47), alcoholism and related disorders (F10, and K70), and head injuries (S06, S07, S09.7, and S09.8).
Demographic and socioeconomic variables
The study population was stratified by sex.
Age was used as a continuous variable in the analysis.
Educational attainment was categorised as ≤9 years (partial or complete compulsory schooling), 10–12 years (partial or complete secondary schooling) and >12 years (attendance at college and/or university).
Geographic region of residence was included in order to adjust for possible regional differences in hospital admissions and was categorised as (1) large cities, (2) southern Sweden and (3) northern Sweden. Large cities were defined as municipalities with a population of >200,000 and comprised the residents in the three largest cities in Sweden: Stockholm, Gothenburg and Malmö.
Neighbourhood deprivation
The neighborhood deprivation index was categorized into four groups: more than one standard deviation (SD) below the mean (low deprivation level or high socio-economic status(SES)), more than one SD above the mean (high deprivation level or low SES), and within one SD of the mean (moderate SES or moderate deprivation level) used as reference group, and also unknown neighborhood SES.
Statistical analysis
Continuous variables are presented as mean and standard deviations, and categorical variables are presented as counts and percentages. Cox regression analysis was used for estimating the risk (hazard ratios (HR) with 95% confidence intervals (CI)) of incident PD in different immigrant groups compared to the Swedish-born population during the follow-up time. All analyses were stratified by sex. Three models were used in our analyses: Model 1 was adjusted for age and region of residence in Sweden. Model 2 was adjusted for age, region of residence in Sweden, educational level, marital status and neighborhood SES, to examine to what extent SES explained the association between country of birth and PD incidence. Model 3 was constructed as Model 2 with the inclusion of relevant co-morbidities to examine if other diagnoses explained the association between country of birth and PD incidence.
We also analyzed age-specific incidence rates for Swedish-born and foreign-born individuals, respectively, and for men and women. Besides, incidence rates over time were analyzed, age-standardized to the European population.
RESULTS
Baseline data of the samples are shown in Table 1a and 1b (n = 2,775,736; 1,302,242 men and 1,473,494 women).Incidence rates per 100,000 person-years were for all Swedish-born 95.9 and for all foreign-born 60.5, and for all men 112.3 and for all women 73.4, with a male/female ratio of 1.53. The incidence rates per 100,000 person-years increased by age: from 50–54 years of age for men from 10.4, and women 5.1, to the highest incidence rates in the year-group 80–84 years of age where men had an incidence of 248.7 and women 141.5, with lower incidence rates in the oldest group (Supplementary Figure 1). The corresponding incidence rates for Swedish-born and foreign-born were for the group 50–54 years of age 8.2 and 4.5, respectively, with the highest incidence rate in the group 80–84 years, 191.3 and 129.4, respectively (Supplementary Figure 2). Regarding incidence rates over time per 100,000 person-years, with age-standardization against the European population in 2013, the rates were for the period 1998-2002 41.2 for men and 32.1 for women, for the period 2003-2007 28.1 for men and 19.9 for women, for the period 2008-2012 29.4 for men and 19.7 for women, and finally for the period 2013-2015 39.1 for men and 25.0 for women (Supplementary Figure 2).
First-generation immigrants and Swedish-born men and number of cases of Parkinson’s disease
First-generation immigrants and Swedish-born women and number of cases of Parkinson’s disease
In Table 1a and 1b data are shown for men and women separately, by immigrant status, and by population and cases (data for the whole sample by population and cases are shown in Supplementary Table 1a and divided by sex in Table 1b). Furthermore, Cox regression with HRs for co-factors (Supplementary Table 2a and 2b) show higher HRs for higher educational levels compared to the lowest level; lower HRs for living in southern or northern Sweden compared to the large cities; higher HRs for being married; lower HRs for unknown neighbourhood socio-economic level; higher HRs for anxiety, depression, dementia and head injuries for Swedish- and foreign-born men and women, while for stroke only for women including both Swedish- and foreign-born; lower HRs for COPD, hypertension, alcoholism for Swedish- and foreign-born men and women, while for diabetes only for Swedish-born men and women.
Risk of PD in immigrants are shown in Table 2a and 2b for men and women, respectively. The risk of incident PD was lower for both immigrant men (HR 0.78; 95% CI 0.74–0.82) and women (HR 0.92; 95% CI 0.87–0.98), with lower risk for most of the male immigrant groups, however in some groups being non-significant, and in some groups on the same level as among Swedish-born. Only one group showed a statistically higher risk of PD, i.e., women from Finland (HR 1.13; 95% CI 1.05–1.23). Groups with especially low HRs of PD were men and women from Southern Europe (HR men 0.52, women 0.45), and men from Latin America (HR 0.51).
The relative risk of Parkinson’s disease in first-generation immigrant men vs. Swedish-born men expressed as hazard ratios (HR) with 95% confidence intervals (95% CI)
Model 1: adjusted for age and region of residence in Sweden; model 2: adjusted for age, region of residence in Sweden, educational level, and marital status, and neighborhood deprivation; model 3: model 2+ comorbidities. Bold values are statistically significant.
The relative risk of Parkinson’s disease in first-generation immigrant women vs. Swedish-born women expressed as hazard ratios (HR) with 95% confidence intervals (95% CI)
Bold values are statistically significant.
DISCUSSION
The main results showed an overall lower risk of incident PD among first-generation immigrant men and women, especially among men. In fact, a statistically higher risk of PD was only present in one group, women from Finland.
There are only few studies on PD among immigrants. When looking at incidence and prevalence of PD the figures from Sweden are rather high compared to global figures. An earlier study from northern Sweden estimated the annual age-adjusted incidence of PD at 22.5/100.000 (with male to female ration 1.2), with cumulative incidence up to 89 years of age for men 3.4%, for women 2.6% (male to female ratio 1.3), and for both sexes combined 2.9% [5]. In that study, the incidence rates per 100,000 person-years for “definite and probable PD” were highest in the age-group 70–74 years, while in our study the peak incidence was found in the age-group 80–84 years. Besides, the male to female ration was somewhat higher in our study, i.e., 1.53 vs. 1.2.
PD was more uncommon in most immigrant groups, but especially among immigrants from South Europe and Latin America, which raises the question to what extent environmental factors, e.g., dietary factors, can influence the PD risk. A review concluded, that “a well-balanced diet rich in a variety of foods, including numerous servings of vegetables and fruits (especially those containing nicotine) and moderate amounts of omega-3 fatty acids, tea, caffeine, and wine may provide neuroprotection” [12]. Besides, a study on the possible role of α-synuclein oligomers stated, that “this suggests that genetic predisposition is important, but not sufficient, in the aetiology of the disease and strengthens the contribution of environmental factors” [13].
For some groups, the risk of PD did not differ significantly from Swedish-born individuals, i.e., among immigrants from the Baltic countries, North America and Russia, and thus in line with the findings of a higher risk among individuals of Caucasian origin [3]. However, these findings only related to some foreign-born immigrant groups of Caucasian origin and not others. Even if the knowledge of genetic factors in relation to PD has increased during later years, a review concluded that “only a fraction of the heritability is known and the relationship between genetics and PD pathology is poorly understood” [14]. Most genetic studies have been performed on Europeans, and some differences between Europeans and Asians have been found as regards the genetic contribution to PD [15].
One factor of possible importance is the healthy migrant effect, i.e., more healthy subjects tend to migrate [16]. As one example, more people who migrate to Sweden from both Western and non-Western countries tend to have a higher educational level than their compatriots in the country of origin. We found that the educational level of both Swedish-born but especially of foreign-born men was higher than in the population in general for these groups. Besides, more cases were registered in the larger cities, where the availability to neurologists is higher.
As regards co-morbidities, PD was associated with higher rates of anxiety, depression, dementia and head injuries. The association between PD with anxiety and depression is known [17–19]. Considering the association between PD and dementia, i.e., two neuro-degenerative diseases, this is not surprising [20, 21]. Regarding dementia among immigrants, we have earlier found dementia to be less common among foreign-born compared to Swedish-born [22]. Furthermore, stroke was more common among cases both in Swedish- and foreign-born women, but not among men; a finding that we could not explain. COPD, which is associated with smoking, showed lower HRs for both Swedish- and foreign-born men and women. In fact, cigarette smoking has been associated with a lower PD risk, with probable effect of nicotine [23]. Diabetes was associated with a lower risk in Swedish-born but not among foreign-born. Actually, diabetes has been associated with a higher PD risk [19], owing possibly to hyperglycemia and hyperglycemic oxidative stress [24].
There are limitations with this study. The number of immigrants as well of cases was rather low in some groups, yielding wide confidence intervals. Besides, we used the level of statistical significance of 0.05, why we recommend that the results for specific groups of immigrants to be interpreted with caution. However, for most immigrant groups the risk of PD was significantly lower than among Swedish-born men and women. We used the Swedish NPR, which includes only diagnoses from hospitals, from both in- and out-patient patients, but not from primary health care. Many patient groups receive their care in primary health care, including COPD, diabetes, hypertension, anxiety and depression [25]. However, when adjusting for comorbidities the results changed rather modestly. The Swedish registers are otherwise in general known to be of high quality [26, 27], but the sensitivity of PD in the NPR is estimated at 70% [28], to be compared to the estimated sensitivity of 75% in the diagnoses of heart failure in registers in general [29]. Changes in diagnostic criteria could lead to a decrease as high as of 36% [30], but we had no possibility to check the criteria being used for the diagnoses from nationwide registers. One important strength is that this is a national study, based on diagnoses from hospitals, both hospital in-care and out-patient care, and PD diagnoses could be considered as being of high validity.
In conclusion, we found a lower risk of incident PD among first-generation immigrant men and women, especially among men, which represents new knowledge. Future studies may examine specific environmental factors associated with PD that may differ between immigrants and Swedes.
Compliance with Ethical Standards
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was not applicable, as the study was based on anonymized data from registers.
The study was approved February 6, 2013 by the regional ethics boards at Lund University (ref nr2012/795).
CONFLICT OF INTEREST
The authors have no conflict of interest to report.
