Epidemiological studies have shown lower age-related prevalence of Parkinson's disease in South Asians, with the rate of prevalence being around 52.7 per 100,000 as compared to a higher prevalence rate observed in populations with European origin, 108-257 per 100,000. Additionally, several studies have seen a higher prevalence of in women which contrasts with global data that observes an overall higher prevalence seen in men. Compared to most of the rest of the world, the South Asian countries (including India, Pakistan, Nepal, Bhutan, Maldives, Afghanistan, Sri Lanka, and Bangladesh) seem to be on the lower end of PD prevalence. However, this is not to say that PD is not of concern in these countries. Over the past couple of years, the rate of Parkinson's has gone up in South Asia meaning that it is of high importance to study this pathological disease in these populations.
Background
Parkinson's disease (PD) is a chronic neurodegenerative disorder caused by the progressive degeneration of dopamine-producing neurons in the substantia nigra, a structure located in the midbrain essential for reward and movement. The rapid deterioration of these dopaminergic neurons leads to both motor and non-motor complications. Being that they are quite visible, the motor symptoms are usually used as a preliminary basis for the diagnosis of PD, particularly deterioration of voluntary movements along with muscular rigidity. Tremor, postural instability, dystonia, and speech disturbances are among the most common motor symptoms in PD cases and are heavily researched in an effort to develop efficient methods of management. Conversely, the non-motor symptoms, including cognitive decline, depression, and sleep disturbances, are not as rigorously studied. Many of these complications develop prior to motor symptoms as early as 10 years before a formal diagnosis and tend to become comparatively more cumbersome as the disease advances. Although, in general, the exact cause of PD is unknown, it is likely that both genetics and environment are contributing factors. Along with around 90 genetic risk variants which account for 16-36% of non-monogenic PD, additional variables such as being a non-smoker can influence the risk a given person has for developing PD.
Pathology
Substantial loss of melanized dopaminergic neurons in the substantia nigra pars compacta (SNpc) is a major characteristic of PD pathogenesis. Many studies have shown that differential prevalence of PD between ethnic groups is due to differences in the number of melanized neurons in the substantia nigra. Most Indians, compared to populations with European origin, have around 40% lower in number of melanized nigral neurons, however, they also tend not to lose these neurons with age. Although Indians do have a lower SNpc volume, this population tends to have a higher neuronal density as well as number of neurons which is hypothesized to be the reason for a lower incidence rate of PD, but this needs to be expanded upon.
Another hallmark of PD pathology is the development of Lewy bodies (LBs) in dopaminergic neurons which are protein aggregates that impair neuronal function. A major component of the structure of these LBs is α-synuclein which becomes phosphorylated followed by aggregation in pathological conditions. Under normal conditions, α-synuclein remains mostly unfolded with some parts of the protein folded into α-helical structures, however, in PD, it assumes a β-sheet amyloid structure which is highly susceptible to aggregation. Due to dietary differences, South Asians tend to consume higher levels of curcumin, a strong anti-oxidant and anti-inflammatory agent, which has been observed to attentuate α-synuclein aggregation. However, variation in LB and α-synuclein pathologies in the South Asian population is heavily under studied and needs to be further elucidated.
Ethnic research limitations Similar to many other diseases, genetic risk factors for PD have been and still are investigated through genome-wide association studies (GWAS). Although the GWAS database has revolutionized genetic studies, they are not an accurate representation of the global population's genetic diversity as most of the samples in these datasets are from populations with European backgrounds. Specifically in Parkinson's, most implicated genes that have been associated with both familial and monogenic forms of PD are prevalent in persons of European descent. Additionally, many of the newly found risk variants screened through GWAS that have been associated with around 25% of the disease heritability are mainly from studies that included only individuals of European ancestry. A lack of diversity in PD research limits the relevance of these findings towards populations of other ethnicities.
Diagnosis Diagnosis for Parkinson's is based on a defined criteria and is usually, as mentioned, based on the first motor symptoms. This includes slowness of initiating voluntary movements and bradykinesia along with one more symptom including tremor or muscular rigidity. Any symptoms that could indicate other diseases, such as parkinsonian syndrome, have to be excluded in the screening process as they have different pathological effects compared to PD. Additionally, there needs to be at least three criteria present such as unilateral onset, persistent asymmetry affecting the onset side more, and a positive response towards treatment with levodopa. Epidemiological differences in PD cases are affected by average knowledge of Parkinson's among populations. Due to a lack of symptom awareness, Parkinson's is oftentimes under-reported in South Asian populations. A study looking into PD knowledge in Asia found that there was not as much awareness regarding non-motor symptoms in the Indian population as compared to East Asian populations. Additionally, Indians were not aware that tremor is not a required symptom to be diagnosed with Parkinson's disease. It is also noted that South Asians, especially the Indian subcontinent has been having younger age of onset of Parkinson's disease as compared to global average. This gap is predicted as high as a decade earlier which is reflected in various recent publications. Because diagnosis partly relies on self-reporting symptoms, this gap in knowledge can make it difficult to get an accurate representation of the variation within the South Asian population as well as become a barrier toward understanding how this disease manifests differently.
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