Parkinson's disease in South Asians
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.
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.
[1] 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.
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.
[2][3] 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.
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.
[6] 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.
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.
[9] 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.
[citation needed] From studies looking at Parkinson's in South Asian populations, ethnic variation has been observed in both motor and non-motor symptomology.
In general, it is likely that mutant GBA accumulates and affects lysosomal function leading to dysregulation of autophagic pathways which is essential for the degradation of α-synuclein in dopaminergic neurons.
Among all of the GBA variants, Indian patients carrying the p. Leu444Pro mutant have observed to have an earlier onset of PD as well as a positive family history.
Mutations in PARKIN have led to a loss-of-function resulting in an accumulation of the ligase's substrate causing the degradation of dopaminergic neurons in the substantia nigra.
[17] A large percentage of the population in South Asia live in rural areas where there is a higher chance of exposure to potential neurotoxins such as pesticides from farming and water sources.
Due to the lighter clothing that farmers opt to wear as well as the longer duration of exposure to both humidity and high temperatures, pesticides are more readily absorbed through the skin in addition to being inhaled.
Specifically, South Asian food is rich in anti-oxidants which has been minimally studied, but thought to potentially play a protective role in Parkinson's.
It is observed that a lower quality of life in Indian PD patients has been linked with depression, cognitive impairment, and a worsening of disease intensity among other factors.
Conversations surrounding mental health are highly stigmatized in South Asian countries and as a result, depression as a symptom is often overlooked especially in the elderly population.
[22] Additionally, socioeconomic factors can play a role in limiting access to advanced care and personalized treatment options as well as increased mortality rates, however, this aspect needs to be investigated in South Asian populations.
Additionally, insulin resistance is able to affect pathways that relate to synaptic plasticity, neuroinflammation, and mitochondrial dysfunction, all of which are implicated in PD pathogenesis.
[30] Hyperglycemia, one of the results of insulin resistance and poor glucose regulation, can lead to mitochondrial dysfunction in the SNpc dopaminergic neurons and therefore, a high production of reactive free hydroxyl radicals which is particularly damaging to this area of the brain.
[31] For South Asian populations, this link is highly relevant in light of their excessive exposure to risk factors contributing to CVD which can result in variation in PD cases.
