Pathological correlates of cognitive decline in Parkinson’s disease: from molecules to neural networks

Author:

Novikov N. I1,Brazhnik E. S1,Kichigina V. F1

Affiliation:

1. Institute for Theoretical and Experimental Biophysics, Russian Academy of Sciences

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder resulting from the death of dopaminergic neurons in the substantia nigra and the appearance of protein aggregates in neuronal cell bodies composed predominantly of alpha-synuclein, known as Lewy bodies. PD is now recognized as a multisystem disorder characterized by severe motor impairment and various non-motor symptoms. Cognitive decline is one of the most common and worrisome non-motor symptoms. Moderate cognitive impairment (CI), diagnosed already in the early stages of PD, usually leads to deep dementia. The main types of CI observed in PD include executive dysfunction, attention, and memory disfunction, visuospatial decline, and verbal deficits. According to the literature, the following mechanisms play a significant role in the development of cognitive dysfunctions in PD: (1) changes in the conformational structure of synaptic proteins; (2) disruption of synaptic transmission; (3) neuroinflammation (pathological activation of neuroglia); (4) mitochondrial dysfunction and oxidative stress; (5) metabolic conditions; (6) functional remodeling of the neural networks. The listed molecular and synaptic changes in the brain can lead to the death of dopamine-synthesizing cells of the substantia nigra and dysfunction of other mediator systems, as well as partial cellular atrophy in the neocortex and subcortical nuclei. As a result, the functioning of neural networks involved in the transmission of information related to the regulation of motor activity and cognitive functions is disrupted. Elucidation of the causes of changes occurring in PD and the search for methods to eliminate them will help create new approaches in the treatment of this disease. The aim of the review is to analyze the pathological processes in the brain that underlie the onset of cognitive impairment in PD. The review analyzes the data obtained both from studies on patients with PD and animal (rodents and primates) models of this disease used for the evaluation of the mechanisms underlying etiology and the development of PD in humans.

Publisher

The Russian Academy of Sciences

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