Neurology (specialist in movement disorders) Speech Therapy Physical and Occupational Therapy Psychiatry (addressing depression and hallucinations) Nutritionist (for swallowing difficulties) Palliative Care (for advanced stages)

Pathophysiology

Etiology

MOTOR

NON-MOTOR

Age exceeding 60 Male gender A familial lineage of Parkinson's disease Exposure to pesticides and herbicides A past history of traumatic brain injury Residence in rural areas, indicating environmental exposure (Ascherio & Schwarzschild, 2016)

Armstrong, M. J., & Okun, M. S. (2020). Diagnosis and treatment of Parkinson disease: A review. JAMA, 323(6), 548–560. https://doi.org/10.1001/jama.2019.22360

Ascherio, A., & Schwarzschild, M. A. (2016). The epidemiology of Parkinson’s disease: Risk factors and prevention. The Lancet Neurology, 15(12), 1257–1272. https://doi.org/10.1016/S1474-4422(16)30230-7

DeMaagd, G., & Philip, A. (2015). Parkinson’s disease and its management: Part 1: Disease entity, risk factors, pathophysiology, clinical presentation, and diagnosis. Pharmacy and Therapeutics, 40(8), 504–532.

Gonzalez-Latapi, P., Cordon, I., & Espay, A. J. (2021). Emerging gene therapies for Parkinson's disease. Current Neurology and Neuroscience Reports, 21(7), 30. https://doi.org/10.1007/s11910-021-01105-z

Hughes, L. E., Altena, E., Barker, R. A., & Rowe, J. B. (2020). Compensatory activity in the frontoparietal network supports executive control in aging and Parkinson's disease. Cortex, 132, 334–348. https://doi.org/10.1016/j.cortex.2020.08.017

Kalia, L. V., & Lang, A. E. (2015). Parkinson’s disease. The Lancet, 386(9996), 896–912. https://doi.org/10.1016/S0140-6736(14)61393-3

Lubomski, M., Tan, A. H., Lim, S. Y., Holmes, A. J., & Davis, R. L. (2022). Parkinson’s disease and the gastrointestinal microbiome. Journal of Neurology, 269(3), 1294–1312. https://doi.org/10.1007/s00415-021-10668-0

Magrinelli, F., Bet, A., Perani, D., Zangaglia, R., & Antonini, A. (2022). Early diagnosis of Parkinson's disease: Clinical and imaging evidence. Neurological Sciences, 43(6), 3521–3532. https://doi.org/10.1007/s10072-022-06245-9

Mortiboys, H., Aasly, J., & Bandmann, O. (2021). Ursocholanic acid and mitochondrial rescue in Parkinson's disease. Movement Disorders, 36(5), 1180–1188. https://doi.org/10.1002/mds.28496

Pagano, G., Taylor, K. I., Anzures-Cabrera, J., et al. (2022). Trial of prasinezumab in early-stage Parkinson’s disease. Nature Medicine, 28(2), 301–308. https://doi.org/10.1038/s41591-021-01646-8

Schweitzer, J. S., Song, B., Herrington, T. M., et al. (2020). Personalized iPSC-derived dopamine progenitor cells for Parkinson’s disease. New England Journal of Medicine, 382(20), 1926–1932. https://doi.org/10.1056/NEJMoa1915872

Neurological: Progressive cognitive decline, dementia Musculoskeletal: Gait instability, falls, contractures Autonomic: Orthostatic hypotension, constipation Psychiatric: Depression, hallucinations, apathy Respiratory: Aspiration pneumonia (resulting from dysphagia)

Falls and fractures, Dementia, Aspiration pneumonia, Urinary tract infections, Pressure ulcers from immobility, Malnutrition arising from dysphagia (Hughes et al., 2020).

Clinical diagnosis is guided by a comprehensive review of history and physical examination in accordance with the UK Parkinson’s Disease Society Brain Bank Criteria. Imaging studies, such as MRI or CT scans, serve to exclude alternative parkinsonian syndromes. A DAT-SPECT scan evaluates dopaminergic function, while genetic testing is advised in cases of early onset or a familial predisposition. Additionally, olfactory testing may provide supportive evidence. It is essential to note that no specific laboratory test can definitively confirm Parkinson’s disease; the diagnosis is predominantly clinical in nature. (Armstrong & Okun, 2020)

Pharmacological

Non-Pharmacological

Gene therapy utilizing AAV2-GAD delivery to the subthalamic nucleus demonstrates promising enhancements in motor function, as evidenced by early clinical trials. Current investigations delve into the potential of LRRK2 gene inhibitors, highlighting their neuroprotective capabilities in individuals harboring distinct genetic mutations (Gonzalez-Latapi et al., 2021).

Stem Cell Therapy - Researchers are exploring the remarkable potential of human pluripotent stem cells to transform into dopaminergic neurons for implantation in the basal ganglia. Promising clinical trials in Japan, particularly those utilizing iPSCs derived from skin cells, have demonstrated encouraging results in small patient cohorts, with minimal risk of immune rejection (Schweitzer et al., 2020).

Immunotherapy, particularly targeting alpha-synuclein, utilizes anti-alpha-synuclein monoclonal antibodies like prasinezumab to mitigate synuclein aggregation, a defining characteristic of Parkinson's disease. In Phase 2 trials (PASADENA), these antibodies demonstrated a commendable tolerability profile, though their efficacy continues to be meticulously evaluated (Pagano et al., 2022).

Gut-Brain Axis and Microbiome - The intricate relationship between the gut microbiome and Parkinson's is increasingly under scrutiny. Recent investigations reveal that imbalances in microbiota may play a pivotal role in the misfolding of alpha-synuclein and the subsequent neuroinflammation. Current trials are exploring the potential of probiotics and fecal microbiota transplantation (FMT) as innovative approaches for symptom management (Lubomski et al., 2022).

Neuroprotective compounds, such as ursodeoxycholic acid (UDCA) and nicotinamide riboside, are being meticulously explored for their capacity to safeguard mitochondria and alleviate oxidative stress. Preliminary trials indicate promise in decelerating the progression of disease (Mortiboys et al., 2021).