Clinical Non-Motor Phenotyping of Black and Asian Minority Ethnic Compared to White Individuals with Parkinson’s Disease Living in the United Kingdom

Study design

This was a cross-sectional analysis from a multicentre, prospective, observational real-life study (UK National Institute for Health Research clinical research network (UKCRN) number: 18278) called “Nonmotor symptoms of Parkinson’s in a multi-ethnic population”, as part of the Non-motor Longitudinal International cohort study (NILS; UKCRN number: 10084). The study was carried out in accordance with the Declaration of Helsinki and authorised by the local ethics committees. All patients gave written consent prior to participating in the study between 27 January 2015 and 1 April 2018. All data were stored at the National Parkinson’s Centre of Excellence, King’s College Hospital in compliance with the National Data Protection Act (United Kingdom (UK) Reg: Z6614305) and compliant with General Data Protection Regulation (GDPR) (EU) 2016/679.

Patients

PD patients based on UK Brain Bank criteria and self-reported ethnicity (Asian, Black, or White) attending clinics across London [17–19].

Assessments

Age, gender, disease duration were noted and levodopa equivalent daily dose (LEDD) calculated [20]. Ethnicity was assigned as per Office for National Statistics from the Census 2011 in England and Wales [17]. The terminology of ethnicity is different across countries; however, as this is a UK based study we elected to align with the official standardised Census criteria. Birth and age when moved to the UK, educational level, civil status, employment activity, potential environmental risk factors, body mass index, cardiovascular and metabolic risk factors were recorded [21].

The following assessments were performed:

Statistical analysis

Normality of distribution was assessed visually by using frequency distribution histograms. Differences between the three ethnic groups were analysed with Kruskal–Wallis tests or 1-way ANOVA analysis of variance if parametric tests were applicable. Post-hoc analysis between pairs of groups were made when the initial test across all groups was statistically significant. Comparison between pairs was performed using Dunn’s (1964) procedure with a Bonferroni correction for multiple comparisons. For comparisons between two ethnic groups the independent-samples t-test or Mann-Whitney U test respectively was used.

To investigate if there were statistical differences in categorical variables between the three different ethnic groups, Pearson’s chi-square or Fisher’s exact test was applied.

All analyses were conducted using Statistical Package for Social Science (version 23.0 for Mac; SPSS). A p-value<0.05 was considered to be statistically significant.

Basic characteristics

Out of 316 patients 45 subjects were excluded (7 patients were diagnosed with atypical Parkinsonian disorder at follow up, 17 patients reported to have mixed ethnic background and 21 had not completed the main outcome tools). Out of 271 patients included, 54 were Asian, 71 Black, and 146 White. Baseline values are summarised in Table 1. The majority of Asian patients were first generation immigrants born in South Asia and India (31.5%), followed by Sri Lanka (14.8%) and Kenya (11.1%) who had moved at an average age of 27.9 years (±13.2) to the UK. Most White PD patients were born in the UK (95.2%). The majority of Black patients were born in Jamaica (38.6%) or Nigeria (21.4%), and had immigrated to the UK at an average age of 26.7 years (±13.6).

The majority of White and Black patients completed high school as the highest degree (50% and 48.6%) while the majority of Asians completed university as highest degree (55.6%) (p < 0.001). There were also significant differences in civil status with 21.1% of Black patients reported to be separated/divorced compared to 7% in the White and Asian population (p < 0.05). There were no significant differences in employment status between the three ethnic groups; among all groups, the majority of patients were retired.

The Black population had a significant shorter disease duration compared to the White population and shorter disease duration and lower LEDD compared to the Asian population.

Motor assessment

The SCOPA-Motor Activities of Daily Living (ADL) score was significant higher in the Asian and Black compared to the White group, SCOPA-Motor scale total score was higher in the Asian compared to the White individual group with a trend towards a higher score in the Black compared to the White group (Table 2).

Burden (severity and frequency) of non-motor symptoms (Non-Motor Symptoms Scale)

The NMSS Total scores were significant higher in the Black and Asian (severe burden) than the White (moderate burden) PD sample (Table 3) [22]. There were no statistically significant differences in NMSS total score and domains between the Asian and Black PD populations.

Asian patients had higher scores on the domains “sleep/fatigue”, “mood/apathy” and “perception/hall-ucinations” than White patients (Table 3).

Significantly worse NMS items were “fatigue” (4.4±3.0 versus 2.5±3.0, p = 0.002), “losing interest in surrounding” (2.7±4.1 versus 1.1±1.9, p = 0.023), “being nervous, worried or frightened for no apparent reason” (3.6±2.7 versus 2.4±1.4, p = 0.016), “being sad or depressed” (3.0±3.8 versus 1.4±2.3, p =0.002) and “difficulties experiences pleasure from usual activities” (1.7±2.9 versus 1.6±0.6, p = 0.025). No significant differences between the items of perception domain.

Individuals in the Black cohort had significantly higher scores in the NMSS domain “miscellaneous” compared to the white group.

Significantly worse NMS items included “pain” (2.8±3.8 versus 1.6±2.7, p = 0.014), and “unexplained change in weight” (1.1±2.3 versus 0.5±1.7, p = 0.002)

Other non-motor measurements

The Black cohort had significantly lower MMSE scores compared to the White cohort but there was no difference on HADS, PDSS and ESS (Table 3). The Asian group had significantly more impairment on the HADS (p < 0.001), with significant higher impairment in the depression domain ((p < 0.001) and a trend to significant difference in the anxiety domain (p = 0.052) and PDSS (p = 0.008) compared to the White group.

Non-declaration of nonmotor symptoms according to the NMSQuest

The frequency of non-declaration of NMS was 38.6% for Black, followed by 37.0% within the Asian and lowest with 29.2 % in the White population (p = 0.381).

Comorbidities

Both the Asian and Black populations reported higher prevalence of arterial hypertension compared to the White population, and the Black population had a significantly higher prevalence of diabetes mellitus (type 1 and type 2) than the White population. BMI and the prevalence of hyperlipidemia were similar across all groups. The prevalence of smoking was similar across all groups, while the White population reported consuming significantly more alcohol than the Black and Asian populations.

Reported exposure to insecticides and pesticides (Asian 20.8%, Black 20.3% and White 22.3%, p = 0.937) was not significantly different across the three ethnic groups (Table 1).

Imaging

In total 63 patients with available MRI Brain studies including axial Proton density/T2 spin echo scan were considered for this analysis. Among those, 30 (46.8%) were White, 14 (22.6%) Asian and 19 (30.2%) Black. On average, the white matter changes in White and Asian PD patients were rated as insignificant while Black patients had on average mild white matter changes. There was no evidence of very severe white matter and basal ganglia lesions in any patients and only 4 patients had basal ganglia changes. The severity of white matter changes was significantly higher in the Black compared to the White and Asian cohort (Mean ARWMC total score 1.2±1.0 versus 0.5±0.8 versus 0.4±0.5 respectively, p = 0.012). There were no significant differences between the White and Asian cohort. Cerebral microbleeds and mean Evan’s Index were similar across the groups (p = 0.254).

The Asian group

We confirmed previous observations that Asian patients have worse motor disability scores than White patients after similar disease duration [12]. Asian patients also had a higher non-motor burden with higher rates of fatigue, sleep dysfunction, anxiety and depression. Fatigue is a common NMS of PD and a fatigue-dominant serotonergic subtype of PD overlapping with somnolence has been proposed [35–40]. The higher prevalence of depression in the Asian population should alert health-care professionals to this group’s increased risk of these neuropsychiatric complications [41].

The Black group

The characteristic features seen in the Black PD population were the higher degree of both motor disability and non-motor impairment. They also had a significantly shorter disease duration than the White population. A more rapid progression in this population has been previously postulated in the South London population [11, 12] but no prospective data is currently available. It is also possible that Black patients are diagnosed later which is supported by the similar Hoehn and Yahr stage and higher rate of non-declaration of NMS. In a US-based study African-Americans were reported to have been less likely to be diagnosed with PD and when diagnosed, were diagnosed at a later stage of disease [42]. It is notable in this context that almost 40% of the Black PD did not report their NMS. This highlights the importance of specifically eliciting these symptoms in black and minority ethnic patients. As recently outlined by Hurt et al., there are several explanations for non-declaration and non-recognition, including cultural factors [43]. We did not address the cause in detail and future studies should address this issue in a multi-ethnic, multi-cultural PD population.

Black patients also reported significantly worse NMSS burden particularly in the items pain and change in weight. Ethnic disparities in relation to pain in the general population have been reported with a general trend that Africans report greater pain and suffering compared to Whites across different conditions and environments [44]. Several causes have been suggested ranging from varying pain thresholds, genetic variability, sociocultural differences, Vitamin D levels and sleep quality [44, 45]. However, in our study we did not specifically address these issues. It is also unclear why Black patients reported greater rates of changes in weight than White patients. This may be related to the higher comorbidity of diabetes mellitus, but we do not know the direction of weight change and comparisons to non-PD populations.

We also found they had lower scores the MMSE than White patients with PD, a finding that has been reported before [12, 47]. However, the fact many Black participants did not have English as their first language and limitations in the use of the MMSE in patients with different educational levels need to be considered in the interpretation of this result. The MMSE was used as this was the preferred option when the NILS study started in 2011. Notwithstanding, this finding might serve to signpost a higher risk of cognitive deterioration in the Black PD group [48]. Whether this suggest a higher rate of the cholinergic cognitive subtype of PD remains to be confirmed [1, 50].

Biomarkers and other contributing factors in relation to ethnic phenotypes

A higher load of white matter changes in the Black compared to the White and Asian cohort was found. Differences between ethnic groups in the presence of white matter changes have been reported although there is controversy in the literature [51, 52]. White matter changes in PD might be partly linked to certain NMS including cognitive impairment, orthostatic hypotension as well as gait disorders [53–55]. In addition, diabetes mellitus and arterial hypertension are also associated with an increased risk of white matter changes. We speculate that the increased white matter changes in our Black PD cohort is therefore likely to be associated with comorbid vascular disorders [12, 56]. Exposure to environmental factors such as insecticides and pesticides has been postulated to be one of the risk factors to develop PD [57]. In our cohort, no significant differences in exposure to insecticides and pesticides were reported, making it unlikely that the observed clinical differences are related to this environmental factor.

Another important aspect that might drive ethnic differences are social factors such as educational levels and civil status; a study on freezing of gait (FOG) for instance has reported that patients with lower education were more likely to suffer from FOG [58]. In our cohort, the Asian population had higher educational levels and also had higher NMSS burden levels compared to the Black population. The differences in educational level are therefore unlikely to explain the observed differences in NMS although access to education and information about PD was not specifically addressed. Furthermore, significant differences in civil status were found (20.8% of Black patients reported to be separated/divorced compared to 7% in the White and Asian population). To date, there is no literature on the potential influence of civil status on the observed ethnic differences.

There are several limitations to this study. To our knowledge, this is the first real-life cohort study in a multi-ethnic population living in the UK. As such we were interested to characterise the population presenting in clinic and participant characteristics were reflective of the clinic population and were not matched for disease duration or severity. The study was also cross-sectional and we were therefore not able to study disease progression prospectively. We also cannot exclude a selection bias in recruitment, although we used unselected NHS clinics to identify and approach participants.

The current study however has demonstrated the feasibility of a study to examine phenotypic differences in a multi-ethnic PD population across London. The findings emphasise differences in phenotype of PD in the BAME populations with greater burden of NMS and motor disability and a higher degree of cardiovascular comorbidity. The findings raise important scientific, social and clinical issues to address the challenges of care delivery in a “hard to reach population” in health services that serve a diverse multi-ethnic population. The results of the study could lead to further work that could drive the development of specific personalised care packages for different ethnic groups, similar to a recent study in pain showing that tailoring care to the needs to specific ethnic groups using a language specific and culturally adopted pain management programme helped to break down cultural barriers but also increase awareness of the cultural perception and experience of persistent pain [59]. Further studies are now needed to confirm the observed differences and assess the precise causes and contributing factors. Furthermore, future studies need to take into account the significant diversity among the overall Asian and Black populations, which could not be addressed in the present study. Finally, these findings set the scene for a large-scale multicentre cohort study with a focus on specific biomarkers and ethnicity which are currently an unmet need.