1. Introduction

Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder characterized by a wide spectrum of motor and non-motor manifestations resulting from the degeneration of dopaminergic neurons in the substantia nigra pars compacta. The disease affects approximately 1–2% of the population over 60 years of age and represents one of the leading causes of neurological disability worldwide [1,2]. Despite significant advances in understanding the molecular and cellular mechanisms of PD, its clinical course remains heterogeneous, posing challenges for diagnosis, prognosis, and therapeutic decision-making.

Traditionally, Parkinson’s disease has been defined primarily by its motor symptoms, including bradykinesia, rigidity, resting tremor, and postural instability. However, growing evidence indicates that non-motor manifestations, such as cognitive impairment, depressive disorders, sleep disturbances, autonomic dysfunction, and sensory abnormalities are integral components of the disease and may precede motor symptoms by several years [3,9,10]. These non-motor features substantially contribute to functional disability and reduced quality of life, often exerting a greater impact than motor impairment alone.

Comprehensive clinical–neurological assessment using validated scales remains a cornerstone in the evaluation of Parkinson’s disease severity and progression. The Unified Parkinson’s Disease Rating Scale (UPDRS) provides a multidimensional assessment of cognitive, daily functional, and motor domains [3], while the Hoehn and Yahr scale is widely used to stage disease severity [4]. Cognitive screening tools such as the Montreal Cognitive Assessment (MoCA) and psychoemotional evaluations, including the Beck Depression Inventory, allow for early identification of non-motor dysfunctions that may influence treatment outcomes and disease prognosis. This article examines the mechanisms, diagnostic approaches, prognostic factors, and therapeutic strategies related to nephrotoxicity in metastatic breast cancer [5,6]. Special attention is given to the integration of prognostic markers and personalized medicine approaches aimed at improving renal outcomes while maintaining effective oncological treatment.

In recent years, increasing attention has been directed toward the role of biomarkers and neurophysiological indicators in Parkinson’s disease. Alpha-synuclein, a key protein involved in the pathogenesis of PD, has been extensively studied as a potential biomarker reflecting neurodegenerative processes. In parallel, disturbances such as olfactory dysfunction and REM sleep behavior disorder have emerged as clinically relevant markers associated with disease progression and neurodegeneration [7].

2. Materials and Methods of Research

A comparative clinical study was conducted involving patients diagnosed with Parkinson’s disease who underwent comprehensive clinical–neurological evaluation prior to treatment initiation. Patients were divided into two study groups: a main group and a comparison group. In addition, a control group of neurologically healthy individuals was included for selected non-motor and biomarker parameters. All participants provided informed consent prior to inclusion in the study, and the investigation was performed in accordance with the principles of the Declaration of Helsinki. Baseline clinical and neurological status was assessed using standardized and validated scales reflecting cognitive, functional, motor, and psychoemotional domains. Cognitive and mental activity was evaluated using Part I of the Unified Parkinson’s Disease Rating Scale (UPDRS I), while activities of daily living were assessed using UPDRS II. Motor function severity was determined using UPDRS III. Disease stage was classified according to the Hoehn and Yahr scale [4].

Depressive symptoms were assessed using the Beck Depression Inventory, and cognitive performance was evaluated with the Montreal Cognitive Assessment (MoCA) [7]. Additional non-motor parameters included olfactory function testing and evaluation of REM sleep behavior disorder symptoms. Serum alpha-synuclein levels were measured as a biochemical marker associated with neurodegenerative processes.

The mean values of UPDRS I–III, Hoehn and Yahr stage, Beck Depression Inventory scores, MoCA scores, olfactory function indices, REM sleep disturbance scores, and alpha-synuclein concentrations were calculated and compared between the main, comparison, and control groups. These data constitute the basis of Table 1, which summarizes the clinical–neurological characteristics of the study groups prior to treatment.

To further characterize disease severity, patients in the main and comparison groups were stratified according to functional impairment levels based on UPDRS I–III scores. For UPDRS I, patients were categorized into mild or moderate cognitive and psychoemotional impairment. For UPDRS II, levels of daily activity limitation were classified as moderate, severe, or associated with loss of independence. For UPDRS III, motor impairment was stratified into moderate, severe, and pronounced motor dysfunction with significant limitation of independent movement.

The distribution of patients across these functional categories was analyzed using absolute values and percentage frequencies. Comparative analysis between groups was performed to identify differences in cognitive, daily functional, and motor impairment severity. These stratified functional outcomes are presented in Table 2, which provides a comparative analysis of functional status levels in the study groups before treatment.

Statistical processing was performed using standard statistical software packages. Quantitative variables were expressed as mean ± standard error of the mean (M±m). Group comparisons of continuous variables were conducted using Student’s t-test. Categorical variables and frequency distributions were analyzed using Pearson’s χ² test. Differences were considered statistically significant at p < 0.05.

3. Results and Discussion

Baseline clinical–neurological assessment revealed significant differences between the main and comparison groups prior to treatment initiation. Analysis of UPDRS Part I scores demonstrated a higher degree of cognitive and psychoemotional impairment in the main group, indicating more pronounced disturbances in mental and emotional functioning. In contrast, patients in the comparison group exhibited significantly lower UPDRS I scores, suggesting relatively preserved cognitive and affective status [4,9]. These findings underscore the heterogeneity of non-motor manifestations in Parkinson’s disease and support previous observations that cognitive and emotional dysfunction often parallels disease severity.

Evaluation of daily living activities using UPDRS Part II showed significantly greater functional limitation in the main group compared with the comparison group. Patients in the main group demonstrated marked restrictions in everyday activities, whereas those in the comparison group retained higher levels of independence. Functional stratification based on UPDRS II revealed that severe limitations and loss of autonomy were predominantly observed in the main group, while moderate impairment was more characteristic of the comparison group. These results highlight the progressive impact of Parkinson’s disease on functional capacity and daily performance. Prior to treatment initiation, a comprehensive clinical–neurological evaluation was performed to assess baseline cognitive, functional, motor, and non-motor characteristics of patients with Parkinson’s disease. Standardized rating scales and laboratory markers were used to obtain an objective and multidimensional assessment of disease severity across the study groups. Comparative analysis focused on mental status, activities of daily living, motor impairment, psychoemotional condition, sleep disturbances, olfactory function, and serum alpha-synuclein levels. The summarized baseline clinical and neurological characteristics of the main, comparison, and control groups are presented in Table 1.

Table 1. Clinical and Neurological Characteristics of the Study Groups Before Treatment (M ± SEM)

As presented in Table 1, the main group exhibited significantly higher UPDRS I–III scores and Hoehn and Yahr stages compared with the comparison group (p<0.05), indicating more severe cognitive, functional, and motor impairment. Beck Depression Inventory and MoCA scores differed significantly between groups, with greater depressive symptoms and cognitive decline in the main group. Serum alpha-synuclein levels were also significantly elevated in patients with more advanced clinical manifestations (p<0.05).

Motor function assessment using UPDRS Part III revealed the most pronounced intergroup differences. Patients in the main group exhibited substantially higher motor impairment scores, reflecting severe bradykinesia, rigidity, postural instability, and gait disturbances. In contrast, motor symptoms in the comparison group were predominantly mild to moderate. [6,9] Functional categorization based on UPDRS III confirmed that severe motor dysfunction and significant limitation of independent movement were exclusive to the main group. These findings indicate that motor symptom severity remains a key determinant of disease burden and functional prognosis. To further characterize disease severity and functional impairment, patients in the main and comparison groups were stratified according to levels of cognitive, daily functional, and motor dysfunction based on UPDRS I–III scores. This functional categorization allowed for a more detailed comparison of impairment severity between groups and facilitated identification of clinically meaningful differences in baseline functional status. The distribution of patients across functional categories for each UPDRS domain is summarized in Table 2.

Table 2. Comparative Analysis of Functional Status Based on UPDRS I–III Scores Before Treatment. UPDRS I – Cognitive and Psychoemotional Function

As shown in Table 2, functional stratification based on UPDRS I–III revealed significantly greater cognitive, daily activity, and motor impairment in the main group compared with the comparison group (Pearson χ², p<0.01). Severe functional limitations and loss of independence were observed exclusively in the main group, whereas patients in the comparison group predominantly exhibited mild to moderate impairment. Disease staging according to the Hoehn and Yahr scale further supported these observations, with patients in the main group demonstrating significantly more advanced disease stages compared with the comparison group. This confirms that the main group represented a clinically more severe Parkinson’s disease phenotype at baseline. Consistent with disease progression, higher Hoehn and Yahr stages were associated with greater impairment across cognitive, functional, and motor domains.

Non-motor manifestations were also more pronounced in the main group. Beck Depression Inventory scores indicated a higher prevalence and severity of depressive symptoms, reflecting the close association between Parkinson’s disease severity and affective disturbances. Cognitive evaluation using the MoCA revealed lower scores in the main group, indicating greater cognitive decline, while comparison group patients demonstrated relatively preserved cognitive function. Olfactory dysfunction and REM sleep behavior disorder symptoms were also more frequently observed in the main group, supporting the concept that non-motor symptoms intensify with disease progression. Biochemical analysis showed elevated serum alpha-synuclein levels in the main group compared with the comparison and control groups. This finding aligns with the role of alpha-synuclein accumulation in Parkinson’s disease pathogenesis and suggests its potential utility as a biomarker reflecting disease severity.

Overall, the results derived from Tables 1 and 2 demonstrate that patients in the main group exhibited a significantly more severe clinical phenotype, characterized by advanced motor impairment, greater functional disability, and pronounced non-motor disturbances. The comparative analysis confirms that Parkinson’s disease severity is closely associated with a multidimensional pattern of neurological dysfunction, emphasizing the importance of comprehensive clinical–neurological assessment. These findings support the use of integrated clinical scales and functional stratification to better characterize disease heterogeneity and inform individualized therapeutic strategies.

4. Conclusions

The present study demonstrates significant clinical–neurological heterogeneity in patients with Parkinson’s disease at baseline, as evidenced by marked differences in cognitive, functional, motor, and psychoemotional parameters between the study groups. Patients in the main group exhibited more advanced disease stages, greater motor impairment, and more pronounced limitations in daily activities, as well as a higher burden of non-motor symptoms, including cognitive decline, depressive manifestations, sleep disturbances, and olfactory dysfunction. Functional stratification based on UPDRS I–III scores proved to be an effective approach for identifying clinically meaningful differences in disease severity. Higher UPDRS and Hoehn and Yahr scores were consistently associated with reduced independence, impaired cognitive performance, and increased motor disability. These findings confirm the multidimensional nature of Parkinson’s disease and emphasize the importance of comprehensive assessment beyond motor symptom evaluation alone.

Elevated serum alpha-synuclein levels observed in patients with more severe clinical manifestations further support the role of this biomarker in reflecting neurodegenerative processes and disease progression. Integration of clinical scales with biochemical markers may enhance diagnostic accuracy and improve prognostic assessment.

Overall, the results highlight the necessity of individualized evaluation and treatment planning in Parkinson’s disease. Comprehensive clinical–neurological assessment, incorporating motor and non-motor features as well as functional stratification, provides a robust foundation for optimizing therapeutic strategies and improving patient outcomes. Future studies should focus on longitudinal evaluation of these parameters to better define disease trajectories and refine personalized management approaches.