Parkinson’s disease (PD) is a progressive neurological disorder characterized by motor dysfunction and neuropathological damage.¹ Risk factors for PD include environmental factors, such as exposure to pesticides and history of cancers or traumatic brain injury,² as well as genetic factors such as mutations in gene loci ɑ-Synuclein, DJ-1, PARKIN, PINK1, and LRRK2.³ Over the years, there has been continuous debate as to which risk factor most influences the development of PD; however, researchers unanimously agree age of onset is one of the most important elements. The difference between patients who develop PD symptoms before age 50 or 55 (these individuals are classified as patients of EOPD, or early onset Parkinson’s Disease) and those who develop symptoms after age 60 (these individuals are classified as patients of LOPD, or late onset Parkinson’s Disease) is notable.⁴

A 2016 study from Canada evaluated 22 EOPD patients and 44 LOPD patients, classifying early onset cases with an age of onset of Parkinson’s disease below age 50 and late onset cases with an age of onset above age 65. EOPD patients had a much longer duration of symptoms at their first official clinical assessment and had more follow-up assessments along with longer survival times (calculated from age of onset [in years]). Despite those statistics, EOPD patients died at a much younger age compared to their LOPD counterparts. EOPD patients were more likely to develop motor complications such as bradykinesia or freezing.⁴ A 2020 study conducted in Rome, Italy, identified 44 EOPD patients and 32 LOPD patients with the same age of onset cutoffs. The groups showed significant differences in clinical analyses, with EOPD patients scoring higher on MMSE (Mini-Mental State Examination) but lower on NMSS (Non-Motor Symptom Scales). Molecular studies revealed lower levels of CSF tau protein in early onset Parkinson’s patients, leading to the researchers suggesting the accumulation of tau protein in the brain causes the cognitive impairment in late onset Parksinson’s (as indicated by their lower MMSE scores).⁵

The pharmacological profile for PD patients also differs depending on age of onset. Since PD involves deterioration of dopamine-producing cells in the brain, levodopa, a dopamine precursor, is the most commonly prescribed anti-Parkinsonian medication. In the perioperative space, levodopa use has been shown to cause hypotension.⁶ Nonetheless, levodopa can effectively treat the bradykinetic symptoms of PD; however, by definition, it increases dopamine release, which can lead to aberrant activity in the striatum and over-suppression of inhibitory pallido-thalamic GABAergic pathways.⁷ This can cause excessive movements in the form of tremors or other dyskinesias. Similar dyskinesias have also been shown to be induced by the anesthetic agent propofol, due to the drug’s inhibitory effects on glutamate transmission.⁶ The 2016 Canadian analysis reported that while EOPD patients had longer disease duration prior to levodopa treatment, they also were on levodopa therapy for more than twice as long as LOPD patients. As such, EOPD patients had a significantly longer duration of symptoms before their disease reached an irreversible level.⁴ Additionally, EOPD patients were more likely to have been prescribed levodopa medication before being admitted to a Parkinson’s-specific clinic. Furthermore, in an older study with 25 early onset patients and 25 matched late onset Parkinson’s patients, researchers discovered EOPD patients experienced a significantly higher rate of developing levodopa-induced dyskinesias. The researchers suggest levodopa therapy be postponed for as long as possible for EOPD individuals.⁸

Similar reports in the available literature find EOPD patients died at a much younger age and had a longer duration of PD symptoms. EOPD patients often have undergone levodopa therapy for much longer, which is consistent with the finding of a slower disease progression in EOPD. Researchers in the field suggest this discrepancy stands because in LOPD patients, onset of disease occurs at a time where there are more comorbidities and less substantia nigra reserve, caused by the neurodegeneration associated with normal aging. In conclusion, results from many studies indicate there are large clinical and biochemical differences between early and late onset patients, which must be considered for the development of personalized treatment plans for individuals suffering from Parkinson’s disease. 

References

1. 1. Kalia, Lorraine V., and Anthony E. Lang. “Parkinson’s Disease.” The Lancet, vol. 386, no. 9996, Aug. 2015, pp. 896–912. DOI.org (Crossref), https://doi.org/10.1016/S0140-6736(14)61393-3 

1. 1. Ascherio, Alberto, and Michael A. Schwarzschild. “The Epidemiology of Parkinson’s Disease: Risk Factors and Prevention.” The Lancet Neurology, vol. 15, no. 12, Nov. 2016, pp. 1257–72. DOI.org (Crossref), https://doi.org/10.1016/S1474-4422(16)30230-7

1. 1. Thomas, B., and M. F. Beal. “Parkinson’s Disease.” Human Molecular Genetics, vol. 16, no. R2, July 2007, pp. R183–94. DOI.org (Crossref), https://doi.org/10.1093/hmg/ddm159 

1. 1. Ferguson, Leslie Wayne, et al. “Early-Onset vs. Late-Onset Parkinson’s Disease: A Clinical-Pathological Study.” Canadian Journal of Neurological Sciences, vol. 43, no. 1, Jan. 2016, pp. 113–19. Cambridge University Press, https://doi.org/10.1017/cjn.2015.244 

1. 1. Schirinzi, Tommaso, et al. “Young-Onset and Late-Onset Parkinson’s Disease Exhibit a Different Profile of Fluid Biomarkers and Clinical Features.” Neurobiology of Aging, vol. 90, June 2020, pp. 119–24. DOI.org (Crossref), https://doi.org/10.1016/j.neurobiolaging.2020.02.012 

1. 1. Shaikh, Safiya I., and Himanshu Verma. “Parkinson’s Disease and Anaesthesia.” Indian Journal of Anaesthesia, vol. 55, no. 3, 2011, pp. 228–34. PubMed Central, https://doi.org/10.4103/0019-5049.82658 

1. 1. Porras, Gregory, et al. “L-Dopa-Induced Dyskinesia: Beyond an Excessive Dopamine Tone in the Striatum.” Scientific Reports, vol. 4, Jan. 2014, p. 3730. PubMed Central, https://doi.org/10.1038/srep03730 

1. Kostic, V., et al. “Early Development of Levodopa‐Induced Dyskinesias and Response Fluctuations in Young‐Onset Parkinson’s Disease.” Neurology, vol. 41, no. 2_part_1, Feb. 1991, pp. 202–202. DOI.org (Crossref), https://doi.org/10.1212/WNL.41.2_Part_1.202