Parkinson’s disease (PD) is diagnosed many years after its onset, under a significant degradation of the nigrostriatal dopaminergic system, responsible for the regulation of motor function. This explains the low effectiveness of the treatment of patients. Therefore, one of the highest priorities in neurology is the development of the early (preclinical) diagnosis of PD. The aim of this study was to search for changes in the blood of patients at risk of developing PD, which are considered potential diagnostic biomarkers. Out of 1835 patients, 26 patients were included in the risk group and 20 patients in the control group. The primary criteria for inclusion in a risk group were the impairment of sleep behavior disorder and sense of smell, and the secondary criteria were neurological and mental disorders. In patients at risk and in controls, the composition of plasma and the expression of genes of interest in lymphocytes were assessed by 27 indicators. The main changes that we found in plasma include a decrease in the concentrations of l-3,4-dihydroxyphenylalanine (L-DOPA) and urates, as well as the expressions of some types of microRNA, and an increase in the total oxidative status. In turn, in the lymphocytes of patients at risk, an increase in the expression of the DA D3 receptor gene and the lymphocyte activation gene 3 (LAG3), as well as a decrease in the expression of the Protein deglycase DJ-1 gene (PARK7), were observed. The blood changes we found in patients at risk are considered candidates for diagnostic biomarkers at the prodromal stage of PD.

Impulsive–compulsive and related behavioral disorders (ICD) are drug-induced non-motor symptoms of Parkinson’s disease (PD). Recently research has focused on evaluating whether ICD could be predicted and managed using a pharmacogenetic approach based on dopaminergic therapies, which are the main risk factors. The aim of our study was to evaluate the role of candidate genes such as DBH, DRD2, MAOA, BDNF, COMT, SLC6A4, SLC6A3, ACE, DRD1 gene polymorphisms in the pathogenesis of ICD in PD. We compared patients with PD and ICD (n = 49), patients with PD without ICD (n = 36) and a healthy control group (n = 365). ICD was diagnosed using the QUIP questionnaires and specific diagnostic criteria for subtypes of ICD. Genotyping was conducted using a number of PCR techniques and SNaPshot. Statistical analysis was performed using WinPepi and APSampler v3.6 software. PCA testing was conducted using RStudio software v1.4.1106-5. The following substitutions showed statistically significant correlations with PD and ICD: DBH (rs2097629, rs1611115), DRD2 (rs6275, rs12364283, rs1076560), ACE (rs4646994), DRD1 (rs686), BDNF (rs6265), these associations are novel in Russian PD patients. Our findings suggest that polymorphisms in DBH, BDNF, DRD2, ACE genes in Russian subjects are associated with an increased risk of ICD development.

Conditions associated with asthenia are usually characterized by increased fatigue, impaired activities of daily living and decreased productivity. In clinical practice it is important to distinguish between idiopathic chronic fatigue (primary or functional asthenia) and chronic fatigue syndrome (CFS). Fatigue can also be classified by neuromuscular and/or cognitive and mental fatigue. The article discusses the neuroanatomical basis and focuses on the neurocognitive theory of pathological fatigue. In addition the relationship between mental stress, fatigue and cognitive impairments such as subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are also discussed. We discuss the rationale that for treatment of asthenic conditions accompanied by cognitive dysfunction it is justified to use combination therapy — fonturacetam and a preparation containing nicotinoyl-GABA and Ginkgo Biloba.

The review presents current data on the peculiarities of the neurodegenerative process in the early stages of Parkinson’s disease (PD) and considers the hypothesis of the presence of body-first and brain-first subtypes of the disease onset. The earliest manifestations of the disease include symptoms such as parasomnia, constipation, hyposmia, anxiety-depressive disorder, daytime sleepiness, color perception changes, cognitive dysfunction, and mild motor manifestations. The diagnosis of PD can be made when characteristic motor manifestations occur: hypokinesia, rest tremor, muscle rigidity. Substantia nigra ultrasound, magnetic resonance imaging in SWI mode, and functional neuroimaging methods are used as confirmatory methods. The approach to the treatment of early stages of PD is age dependent. Patients over 70 years of age are recommended to start therapy with levodopa; younger patients – with dopamine receptor agonists (ADR), amantadines, MAO-B inhibitors. The mechanisms of ADR action, the possibility of their influence on the motor and non-motor symptoms of PD are analyzed. A special place is given to piribedil, which, due to the dual mechanism of action, has a positive effect on cognitive functions, depression, apathy, as well as a minimal effect on daytime sleepiness.

The article is devoted to the phenomenon of the emergence or enhancement of creative abilities during therapy in some patients with Parkinson’s disease (PD). The article discusses the possible pathogenetic causes of this phenomenon, the connection with impulsive-compulsive disorders (ICD). All PD patients who are addicted to one type of creativity are characterized by increased motivation, forcing them to spend hours doing what they love, the time of which coincided with the start of dopaminergic therapy. There is a fine line between the emerging «passion» for art and CAVIAR, which is determined by the dose of Antiparkinsonian drugs, genetic characteristics, and personal characteristics. The issue of the emergence of creativity in the work of patients with PD remains controversial, and most studies indicate a deterioration in divergent thinking, which is a criterion for creativity. The results of the observation of artists suffering from PD showed changes in the style of their work against the background of the disease, the appearance of an emphasis on color, changing the brightness and spectrum of the color palette, moving to more abstract images. Among the factors that can influence creative activities, such as pre—existing skills or abilities in relation to a particular type of art, taking dopaminergic drugs, their dose, the preservation of cognitive functions, family support, and the social environment are discussed.

Parkinson’s disease (PD) is diagnosed by the onset of motor symptoms and treated long after its onset. Therefore, the development of the early diagnosis of PD is a priority for neurology. Advanced methodologies for this include (1) searching for patients at risk of developing prodromal PD based on premotor symptoms; (2) searching for changes in the body fluids in these patients as diagnostic biomarkers; (3) verifying the diagnosis of prodromal PD and diagnostic-value biomarkers using positron emission tomography (PET); (4) anticipating the development of motor symptoms. According to our data, the majority of patients (n = 14) at risk of developing PD selected in our previous study show pronounced interhemispheric asymmetry in the incorporation of 18F-DOPA into dopamine synthesis in the striatum. This was assessed for the caudate nucleus and putamen separately using the specific binding coefficient, asymmetry index, and putamen/caudate nucleus ratio. Interhemispheric asymmetry in the incorporation of 18F-DOPA into the striatum provides strong evidence for its dopaminergic denervation and the diagnostic value of previously identified blood biomarkers. Of the 17 patients at risk of developing prodromal PD studied using PET, 3 patients developed motor symptoms within a year. Thus, our study shows the promise of using the described methodology for the development of early diagnosis of PD.