Development of early diagnosis of Parkinson's disease: Illusion or reality?

Abstract

The fight against neurodegenerative diseases, Alzheimer disease and Parkinson's disease (PD), is a challenge of the 21st century. The low efficacy of treating patients is due to the late diagnosis and start of therapy, after the degeneration of most specific neurons and depletion of neuroplasticity. It is believed that the development of early diagnosis (ED) and preventive treatment will delay the onset of specific symptoms. This review evaluates methodologies for developing ED of PD. Since PD is a systemic disease, and the degeneration of certain neurons precedes that of nigrostriatal dopaminergic neurons that control motor function, the current methodology is based on searching biomarkers, such as premotor symptoms and changes in body fluids (BF) in patients. However, all attempts to develop ED were unsuccessful. Therefore, it is proposed to enhance the current methodology by (i) selecting among biomarkers found in BF in patients at the clinical stage those that are characteristics of animal models of the preclinical stage, (ii) searching biomarkers in BF in subjects at the prodromal stage, selected by detecting premotor symptoms and failure of the nigrostriatal dopaminergic system. Moreover, a new methodology was proposed for the development of ED of PD using a provocative test, which is successfully used in internal medicine.

Intranasal insulin improves mitochondrial function and attenuates motor deficits in a rat 6‐OHDA model of Parkinson's disease

“…The most important mechanisms implicated in development of PD include aggregation of misfolded proteins, mitochondrial dysfunction, energy failure, oxidative stress, and dysregulated calcium homeostasis 3 . Current research extensively focuses on finding new early diagnostic approaches and introducing molecular targets for disease‐modifying treatments specified for underlying causes of PD and reducing DA neuronal loss 4–6 …”

Parkinson‐like early autonomic dysfunction induced by vagal application of DOPAL in rats

“…The evidence from this investigation definitely extends our current understanding of the etiology of PD that may initiate from the peripheral site due presumably to an unusual metabolism of DA and accumulation of DOPAL, consequently mediating α‐Syn aggregation and causing further dysfunction of central dopaminergic system through toxic effect of DOPAL and α‐Syn on axonal transportation, eventually causing an early autonomic dysfunction of BP regulation. This autonomic failure of BP regulation of PD is strongly supported by recent finding that lower urinary track and gastrointestinal dysfunction are common in early PD 52–54 and these non‐motor deficits of during early PD development such as autonomic dysfunction are well described in a recent review article 55 . The better understanding of early autonomic dysfunction and underlying mechanisms is definitely required to offer better therapeutic options to PD patients 56,57 …”

Estimating economic efficiency of preclinical diagnostics of Parkinson's disease with cost-utility approach

“…In this paper we engage with an evolving innovative method of preclinical diagnosis of PD, which consists, first, in searching for biomarkers in body fluids, mostly blood, of patients with premotor symptoms included into the group at risk of PD at prodromal phase and, second, in prescribing them neuroprotective therapy (Ugrumov 2020;Kim et al 2020).…”

“…Consequently, a great deal of attention is being paid not only to early diagnostics, which usually means diagnosing at a clinical stage, when the symptoms of PD are already obvious and the irreversible loss of dopaminergic innervation is in progress, but also to the disease detection at an earlier, presymptomatic stage. Presently neurobiologists discuss prospects of the development of an innovative technology of presymptomatic diagnostics of PD -at a prodromal stage, before clinical phase; such technology, when applied to at-risk individuals in combination with the subsequent neuroprotective therapy, is bound to add years to the patients' lives and improve their quality of life (Ugrumov 2020). The disease detection at that stage would slow down its progress while also reducing the costs related to the treatment and rehabilitation.…”

“…This study relies on the methodology of diagnosing PD at prodromal phase proposed by the academician M.V. Ugrumov's group (Kim et al 2020;Ugrumov 2020), the development of which, at the time of this study, is yet at a preclinical stage. The new methods involve tests, including the ones to detect specific blood markers, that would allow to identify risks of developing PD at a presymptomatic phase.…”