Abstract
The modern concept of Parkinson’s disease (PD) has changed substantially even in the last 20 years. PD is now regarded as a heterogeneous syndromic condition rather than a disease, highlighting the need to further disentangle subgroups within this condition to advance our understanding and improve management of this second most common neurodegenerative condition worldwide. Ethnicity adds an intriguing aspect. It has become evident in other neurological conditions and preliminary data in PD that ethnicity might have an important impact on relevant factors such as genetic, epigenetic, environmental, cultural and socioeconomic factors, which have all been suggested to play a role in the pathophysiology and symptom expression in PD.In this thesis a multicenter study across London recruiting a multi-ethnic PD population was performed allowing the comparison of clinical profiles between Asian, Black African and Caribbean and White PD populations with a focus on non-motor symptoms (NMS).
Firstly, the results from this thesis suggest a specific phenotypic variant that is overrepresented in the Black African and Caribbean and Asian compared to the White PD population. The proposed Black African and Caribbean PD phenotype was characterised by shorter disease duration, greater impairment in activities of daily living, greater non-motor burden on the non-motor symptoms scale (NMSS) and higher prevalence of comorbidity (arterial hypertension and diabetes mellitus). On the other hand, the phenotype among Asian patients appears to have a greater motor impairment and worse overall non-motor burden on the NMSS scale. Underpinning factors may be driven by fatigue, sleep dysfunction, anxiety and depression and greater comorbidity (in particular arterial hypertension).
As next step, relevant biomarkers (MRI and DaTSCAN imaging and COMT genetics) were explored which might help to distinguish between the different symptom expressions of these phenotypes and advance understanding of the underlying pathophysiology.The MRI based data suggested a higher burden of white matter changes (WMC) in the Black African and Caribbean PD cohort compared to the White and Asian cohort. None of the included patients showed signs of cerebral microbleeds and the Evan’s index as measure of ventricular enlargement(thought to be an index of neurodegeneration) was within normal range in all three ethnic groups. Subsequently, dopamine receptor presynaptic imaging using DaTSCAN data suggested equivalent reduction on DaTSCAN uptake in the three groups indicating that it is unlikely that the observed clinical differences in motor and non-motor profiles are explained by differences in the presynaptic dopaminergic depletion in the basal ganglia. Furthermore, even though the interpretation of data was limited by the small sample size and within ethnic group analysis was not possible, overall the COMTrs4680 polymorphism data suggested that the “GA” allele which translates into an intermediate COMT activity is the most frequent allele among the White population while the “GG” allele corresponding to a high COMT activity is more prevalent among Asian populations. No link was found between WMC on MRI brain scan, ventricular sizes or COMT activity and NMS assessed with NMSS.
On the other hand, differences in dietary habits between different ethnic groups affected with PD have been shown in this study and may be important to consider in the context of personalised medicine delivery.
Finally, a focus group was conducted to address the data gathered from this research and to explore the barriers and possible solutions. One of the strongest message was that personalised guidance is one way forward to improve health inequalities among patients from different ethnic groups.Taken together these findings suggest that specific phenotypes of PD do exist in the non-white PD populations as indeed suggested originally by studies in London by Chaudhuri, Hu and Brooks.
The investigations conducted in this thesis will help further important knowledge about clinical and biomarker base differences in the expression of PD among different ethnic populations. The findings of this thesis, therefore, lay the grounds for a large-scale multicentre cohort study with a focus on specific biomarkers and ethnicity, currently an unmet need.
| Date of Award | 1 Jun 2019 |
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| Original language | English |
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| Supervisor | Kallol Ray Chaudhuri (Supervisor) & Richard Brown (Supervisor) |