In this study, we collected data from individuals with PD and compared it with a group of HCs matched by age and sex. Notably, significant differences in several biomarkers were observed between the PD patients and the control group. We then utilized logistic regression, correlation analysis and nomogram analysis to investigate factors associated with PD, identifying inflammatory markers and blood lipid profiles as key contributors to the disease. Our thorough examination highlighted the significance of TC, NHR, and LHR as pivotal factors for diagnosing and tracking PD progression.
Blood lipids, encompassing TC, TG, LDL and HDL, are integral to the pathogenesis of neurodegenerative diseases, as evidenced by substantial research [25, 26]. Disruptions in lipid metabolism can lead to an overproduction of free radicals, which in turn compromise the body's antioxidant defenses. This results in heightened oxidative stress, causing alterations in blood rheology, thickening of the microvascular walls, and the development of vitreous lesions. These changes can culminate in vascular occlusion, leading to cerebral ischemia, hypoxia, and neurodegeneration [27]. Moreover, dyslipidemia is recognized as a potential harbinger of motor symptoms in patients with PD [28]. Existing literature on the link between blood lipids and PD yields mixed results. While Lu et al. [27] reported no significant differences in TC, TG, and LDL levels between PD patients and healthy controls, Saedi et al. [29] observed significantly reduced serum concentrations of these lipids in PD patients, including TG, LDL and TC. There is a hypothesis that inadequate or dysfunctional HDL within the brain contributes to neurodegenerative pathology [26, 30]. In the current study, multivariate regression analysis identified TC was a significant predictor in the diagnosis of PD. We found that patients diagnosed with PD had lower TC levels than those in the control group, consist with the results from Saedi’s research [29]. Furthermore, a significant correlation was observed between TC levels and the severity of PD as assessed by the UPDRS scores. This correlation indicates that TC may be a potential biomarker for the progression of PD. Therefore, blood lipids have important roles in the progression and pathogenesis of PD.
Recent studies have firmly linked inflammation with the pathogenesis of PD [31, 32]. The LHR is a novel indicator of inflammation, which extends to metabolic syndrome (METS) and chronic obstructive pulmonary disease, where it is an independent risk factor [22]. METS has been linked to increased leukocyte and lymphocyte counts, suggesting LHR’s importance in assessing its presence and severity [33]. Studies have also shown that both the LHR and the NHR are predictive of METS in women, irrespective of other risk factors [34]. In the context of PD, lymphocyte counts are reduced, particularly CD4+ T cells, CD19+ B cells, and Treg cells [35]. Analysis of 123 newly diagnosed PD patients showed an inverse relationship between lymphocyte and neutrophil percentages and the motor score on the UPDRS [36]. While a cohort study indicated that higher lymphocyte counts are tied to a lower PD risk, it was acknowledged to have confounding factors [37]. However, the indicator LHR in PD research has not yet been investigated. In this study, through multivariate logistic regression analysis, we found that PD patients had lower LHR than controls, positing it as a protective factor. Correlation analyses, including Pearson and Spearman, demonstrated significant negative correlations between LHR and UPDRS scores, the H&Y staging system, and disease duration in PD patients. Collectively, these findings suggest that the LHR could serve as a potential biomarker, aiding in the diagnosis of PD and potentially predicting the progression of the disease.
A previous study found that NHR could predict METS in women [34]. NHR is also a biomarker for nascent METS [38]. In a comparison study about acute myocardial infarction, NHR had a superior prognostic value in elderly patients [39]. However, there are few studies about NHR in PD. In this study, we discovered that the NHR was significantly lower in patients with PD compared to HCs. Multivariate logistic regression analysis further supported NHR as a protective factor. Additionally, Spearman correlation analyses revealed significant negative correlations between NHR and certain components of the UPDRS scores. These findings suggest that the NHR could serve as a potential biomarker for predicting the progression of PD
Many studies have shown that the MHR is closely related to the occurrence, progress and prognosis of cardiovascular, immune system diseases and rheumatic diseases [14, 15]. In this study, when we compared the two groups, we found that the MHR acted as a protective factor against PD, with significantly lower levels observed in patients diagnosed with PD. However, MHR did not emerge as an independent factor that could influence the diagnosis of the disease. Additionally, no significant differences were found in UA levels, the LMR and NLR between PD patients and HCs. However, both the NLR and LMR demonstrated significant correlations with disease duration in PD patients, indicating a potential link that warrants further investigation to understand the underlying mechanisms.
In summary, our study delineated the roles and clinical relevance of inflammatory markers and lipid profiles in the diagnosis and progression of PD. Specifically, the LHR and NHR emerged as novel biomarkers with potential implications for both diagnosing PD and tracking its progression.
Limitations
Nevertheless, this study has certain limitations. Firstly, it was conducted as a single-center pilot study, which may affect the generalizability of the findings. Secondly, the research did not delve into the cellular and molecular mechanisms that could explain how inflammation impacts the development and course of PD, an area that requires further exploration.