Our study reports some key findings highlighting differences in PD presentation and care among local PD Emirati population versus a comparator Expat PD group in UAE. These are:
1. The PD Emirati cohort tended to have a larger proportion of Young Onset of Parkinson’s (YOPD) compared to Expats
2. Emirati female patients had more frequent Lower limb tremor dominant subtype (25%) compared to (12.56%) and LLT group have higher nocturnal, radicular and fluctuation related pain.
3. Emirates PD significantly low age compared to Expat with similar disease severity (HY stage) with a significant lower duration of disease which may be suggestive of a faster disease progression
4. Emirate PD have a significantly low LED inspite of similar HY stage with Expat PD suggesting possible under treatment although dis duration may be a confounder
5. NMS profiles, Qol, are similar across both groups
6. There is a major level of unawareness of advanced therapies across the Emirate PD
We report that the average age of PD Emiratis was significantly lower than the combined expat group. This suggests a higher prevalence of YOPD in this group and as proposed by Khalil et al 7 (2020) this may underpin a genetic causation or predisposition possibly contributed to by consanguinity in Arab population although this was not specifically studied and is certainly worthy of further larger suitable powered clinical genetic cohort studies. 93.8% of Emiratis presented to our clinics were YOPD within 1-5 years’ duration. It is also considered that the general age of the Emirate population tends to be lower and as such there may be a bias to this observation.
When data on the Emirate PD is examined in a more granular fashion, then it emerges that the Emirate PD inspite of lower disease duration have similar HY stage compared to the expat group and similar burden of overall NMS scores. A faster disease progression in this group therefore could be proposed on the basis of this observation although lower LED intake in the Emirate group could be a confounder.
The occurrence of higher proportion of LLT in emirate female PD is of interest. LLT has been specifically described to occur in some genetic variants of PD such as in Parkin mutation31 as well as in those with LRRK232 and the data therefore needs more specific observation , genetic and biomarker analysis as well as clinical follow up of this specific cohort . There was a higher representation of nocturnal, fluctuation and radicular pain in the LLT group. This is a preliminary finding and needs to be looked into it in more granular details. Lower back pain as well as shoulder pain (variants of musculoskeletal and radicular pain) have been reported in PINK1 and GBA mutation related PD cases33 Fluctuation is often seen at a greater level in YOPD and parkin positive cases. These factors therefore need exploring.
On the whole the overall NMS burden were similar cross both groups and given that the emirate PD group had a significantly lower disease duration this may mean that the clinical PD phenotype in this group may have a greater representation of the recently described NMS endophenotypes34. Greater understanding and clarity around this pattern of endophenotype would be important to assign sub type specific treatment and delivery of personalized medicine35 in this group.
Finally, we consider vignettes of care delivery of PD across both groups. The Emirates saw more neurologists and inspite of seeing at least 3 neurologists there was a significant delay in initiation of treatment even after diagnosis in UAE PD patients both Emiratis and Expats. Surprisingly 33% Emiratis were not on any treatment even after 2-5 years of diagnosis and this observation is in conflict with the wider consensus that treatment in PD ought to be started at diagnosis as patients otherwise report progressive deterioration in QoL (Grosset et al 24 PDLIFE). The issue here may be the provision of care delivery for PD at an early stage.
Delivery of care in PD is also underpinned by successful provision of advanced infusion (apo IJLI) and surgical treatments. Here awareness of patient about these treatments is paramount and our data suggest that only 25% of Emiratis are aware of the deep brain stimulation surgery (DBS), compared to 69% of Expats. Interestingly only 2% of Emiratis are aware of Apomorphine infusion treatment (CSAI), compared with 32% of Expats. Surprisingly None (0%) of Emiratis when compared to 13% of expats, aware of intrajejunal levodopa infusion (IJLI). Out of 171 (our study sample) only 8% were treated with device aided therapies despite the fact that nearly 50% were eligible based on delphi 5-2-1 criteria30. This may be due to lack of awareness, or specialist skills or experience or advanced device aided therapy (DAT) treatment guidelines to implement these therapies. Some of the Arabic patients and care givers struggled with clinical scales/questionnaires being in English perhaps Arabic translated ones would be beneficial.
The findings consolidate several key unmet needs related to MENASA countries as articulated in the 2020 paper by Khalil et al.7 In the Emirate PD well controlled longitudinal cohort studies needs to be undertaken seeking genotype phenotype correlations from a care perspective, awareness for advanced therapies needs to be improved and this needs to be a multilevel educational exercise related to both patients and health care professionals. Such access to therapies can be improved by implementation of a culturally bespoke local clinical guideline for pharmacological as well as non-pharmacological therapies for PD.
Another striking feature of our study we would like to highlight is Emotional Well Being AND Social Stigma predicts QOL in Emiratis, lack of social supports impairs Quality of Life in Expats and anxiety is a predictor of sexual dysfunction especially in Emiratis. Pain in Parkinson’s is independent of disease severity so is with disease duration. Nocturnal pain (NP) is found to be higher in all the PD Subtypes whereas Radicular pain dominates Tremor Dominant subtype.
Why early diagnosis and treatment important in PD?
Parkinson’s disease is a progressive neurodegenerative condition attributed to progressive loss of dopaminergic neurons emerging evidence supports early intervention may help preserving the functioning of neurons helps in slowing disease progression and improving overall quality of life36 early treatment depends and relies on early diagnosis, an UK autopsy study of 100 subjects who had been diagnosed with PD found a misdiagnosis rate of 24%37 another study 38 showed nearly 47% of PD diagnosis are incorrect when performed in primary care setting and by non-movement disorder specialists. It is necessary that the required skill set and resources to be refined as early detection and treatment have potential to improve the experience and quality of life39.
Clinical benefits of early diagnosis and treatment in PD?
Several studies demonstrated clinical benefit of early treatment. A multicentre controlled clinical trial of Selegilline for 24 months’ follow-up on 800 patients in 1987 demonstrated a delayed onset of disability and reduction in motor function (UPDRS) and requirement of Ldopa40. Early Parkinson's disease can be managed successfully for up to five years with the use of ropinirole alone and supplementing it with levodopa if necessary. This result is observed in a 5 year follow up study comparing the role of ropinorole vs LDOPA and Bensergide41. In another study, Rasagiline treatment demonstrated significant improvement in motor (UPDRS) and no change in onset/frequency of adverse events in a 26-week follow-up study comparing Rasagiline vs Placebo42. A 46-month SPECT study of individuals treated with Pramipexole and carbidopa levodopa revealed that the pramipexole-treated group had less dopaminergic neuron degeneration than the carbidopa-treated group, with identical UPDRS scores in both groups43. Follow-up for 24 months, in a PET study of patients treated with ropinirole and carbidopa levodopa, the pramipexole-treated group showed decreased dopaminergic neuron degeneration, with equivalent UPDRS ratings in both groups44. A 42-week follow-up study of varied multiple doses of carbidopa levodopa revealed a dose-related improvement in motor UPDRS scores45. With pramipexole, there was a reduction in dyskinesia and wear-off, but the L-dopa group had a better overall score and motor score, as well as fewer side effects (freezing, somnolence, and edema)46. In a meta-analysis of 5247 individuals treated with dopamine agonists and levodopa, patients treated with dopamine agonists had fewer motor problems (dyskinesias, dystonia) than patients treated with levodopa47. Individuals treated with MAO B inhibitors had improvements in both motor scores and activities of daily living in a meta-analysis study of 3525 patients treated with MAO B inhibitors and levodopa48. Rasagiline 1mg and 2mg were compared to placebo in a 72-week follow-up study. With rasagiline 1 mg but not with 2 mg dosage, the early-start group had better UPDRS scores than the delayed-start group49. The 6.5-year extension of the TEMPO research confirmed that the early treated group had less UPDRS score degradation than the delayed onset group50. The intervention group experienced a slow onset of dyskinesia and had a higher frequency of dyskinesia51. L-dopa improves mobility and gives higher quality of life than dopamine agonists (DA) and monoamine oxidase type B inhibitors, according to a 36-month follow-up study of 1620 patients comparing levodopa and dopamine agonists and MAOB inhibitors52 all these studies (randomised clinical trials and meta-analysis) summarised in ( table-3) supports treatment should be initiated at the time of diagnosis, delaying the treatment has worst prognostic implications (table 3).
Economical benefits of early diagnosis and treatment in PD?
Early intervention is likely to have a significant impact on healthcare costs, as well as societal impact several studies showed impact of social healthcare burden and economic costs and quality of life is severe in the later stages of the disease, when symptoms are at their most severe, necessitating more healthcare services or caregiver support39,40,53,54. Motor difficulties (motor fluctuations, dyskinesias, and dystonia, which manifests as uncontrollable and sometimes painful muscular spasms) have been recognised as variables contributing to the rise in PD-related expenditures. Social, healthcare burden and economic costs and quality of life in patients with advanced Parkinson’s disease (APD)53,54,55
Patients with Parkinson's disease (PwP) experience more unpredictable and troublesome motor and non-motor fluctuations as they progress through advanced stages, with the emergence of severe motor (progressive disability) and non-motor symptoms such as mood, cognitive, and behavioural problems, causing a severe impact on QoL and necessitating more healthcare services or caregivers53,54,55.
According to a study by Schrag et al,53 the overall burden of Parkinson's disease and healthcare resource consumption expenses grew dramatically as the disease progressed with advanced Parkinson’s disease (APD). Annual costs for early Parkinson's disease were €2,110, but for advanced Parkinson's disease they were about twenty times higher (€38,625), and majority of patients with advanced disease not on any device aided therapies (DAT) elderly over 70 years old53. A Spanish study by Zecchinelli et al.56 revealed roughly 30% of Parkinson's patients are in advanced stages, and the cost of illness rose sharply, primarily due to costs linked with in-patient treatment and nursing homes because advanced-stage patients are bedridden, wheelchair-bound, or hospitalised57,58. The primary drivers and determinants of the socio-economic burden of PD, were hospitalisation, nursing care, drug costs, indirect costs (loss of work etc.) predictors of quality of life, societal socio-economic impact healthcare burden and QOL in PwP59,60,61 ( Fig 7)
Study by Popov et al.62 looked at costs of PD illness and societal burden in a cohort of 100 patients showed over all annual burden of 1 billion euros with direct costs accounting to 67% and indirect costs accounting 33% and main drivers of the burden being informal care and drugs63. Another UK study by Mccrone 64 et al. showed informal care compared to formal ( 80% vs 20%) impact on societal burden and main predictors being male gender, level of disability and non-motor symptoms like depression64. Adherence to oral medications especially in elderly patients with advanced disease where they have to take several pills multiple times strong predictor of socio-economic burden 61% of PD patients were non-adherent to oral therapy and medical costs were significantly higher among non-adherent versus adherent ($15,826 vs $9,228)65. A multicenter (France, Germany and UK) observational study by Pechevis et al.66 showed dyskinesia (motor complications measured using UPDRS scale) was associated with significant socio-economic and societal burden and increasing total healthcare costs with each unit increase in dyskinesia score lead to 562 euros additional costs per patient over a 6 month period66.
The economic and clinical evidence gathered in literature shows and confirms that early diagnosis and initiation of treatment is crucial, halts risk of disease progression, reduce the effects on QOL, potential lowering treatment costs if possible non oral therapeutic device aided therapies offered to patients as they progress to advanced stage before significant deterioration has occurred and patients QOL and well-being are improved when Multidisciplinary care approach and timely referrals to movement disorders specialist with expertise in PD as selection of patients for advanced device aided therapies ( IJLI, CSAI,DBS) likely to be most effective and patients likely to be more complaint with these therapies.