Lower serum triglyceride levels linked to more severe motor performance in Parkinson’s disease

This cross-sectional study enrolled 279 idiopathic PD patients from the Department of Neurology of Beijing Tiantan Hospital, Capital Medical University, from May 2016 to August 2018. Patients who met the clinically definite PD based on 2015 Movement Disorder Society (MDS) Clinical Diagnosis Criteria were included [13]. The exclusion criteria included (1) an uncertain PD diagnosis or suspicion of atypical parkinsonism (multiple system atrophy, corticobasal ganglionic degeneration, or progressive supranuclear palsy) or second parkinsonism syndrome (vascular, drug-induced, toxin-induced, or postinfectious parkinsonism); (2) a history of cerebral infarction or coronary atherosclerotic heart disease; or (3) a history of moderate-to-severe head trauma, hydrocephalus, brain surgery, or brain tumor. This study was approved by the Ethics Committee of the Beijing Tiantan Hospital and was performed in accordance with the Declaration of Helsinki. Informed consent was obtained from either the participant or their closest relative.

The demographic data (age at admission, sex, weight and height, and disease duration) of all the enrolled PD patients were collected. The use of statin or other lipid-lowering medicines was also recorded. The severity of PD was assessed by Hoehn–Yahr (H-Y) staging and the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) total score. The subscores for tremor (items 3.15, 3.16, 3.17, and 3.18), rigidity (items 3.3), bradykinesia (items 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, and 3.14), and gait/postural instability (items 3.10, 3.11, and 3.12) were obtained from the MDS-UPDRS III. Cognition was assessed by the Montreal Cognitive Assessment (MoCA). Mood was assessed by the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). Motor assessment was performed in an off-medication state, which was defined after 12 h of overnight withdrawal from antiparkinsonian medications; however, cognition and mood assessments were performed in on/off-medication state (the on-medication state was defined after 1.5–2 h from antiparkinsonian medications intaking). The levodopa equivalent daily dosage (LEED) was calculated as levodopa dose + levodopa dose × 1/3 if on entacapone + piribedil (mg) + pramipexole (mg) × 100 + selegiline (mg) × 10 + amantadine (mg) + controlled-release levodopa (mg) × 0.75 [14]. All individuals with PD were assessed by experienced neurologists.

Fast serum samples were obtained in the morning and serum levels of lipid profiles, including TC, LDH-C, HDL-C, TG, Apo-A1, and Apo-B, were measured in the clinical laboratory of the Beijing Tiantan Hospital. The levels of serum TC, TG, LDL-C, and HDL-C were determined using enzymological methods while the levels of Apo-A1 and Apo-B were determined using immunoturbidimetric assays. Serum uric acid and homocysteine were also detected.

All statistical analyses were performed in SPSS 24.0. The Kolmogorov–Smirnov test was used to check the distribution of the data. Continuous variables were expressed as means and standard deviation (SD) or median and interquartile range (IQR) accordingly to normality of the data, and categorical variables were reported as numbers and percentages. Student’s t-test and Mann–Whitney U test were used for comparison of normally and nonnormally distributed data between males and females, respectively. Chi-square test was used to evaluate differences in categorical variables.

We assessed the association between lipid profiles and motor performance in PD using univariate and multivariable linear regression models. We used motor performance (MDS-UPDRS III total scores, tremor subscores, rigid subscores, bradykinesia subscores, or gait/postural instability subscores) as the dependent variable, and the serum lipid levels (TG, TC, LDL, HDL, Apo-A1, or Apo-B) as the independent variables. Data with missing outcomes were removed from the analysis. Two multivariable linear regression models were conducted. Model 1 accounted for demographic and clinical variables, including age, education, body mass index (BMI), age at onset, disease duration, MoCA score, HAMA score, HAMD score, LEED, and use of lipid-lowering medication. Model 2 additionally accounted for other biomarkers reported to affect motor performance in PD patients, such as uric acid and homocysteine [15]. Unstandardized (B) or standardized coefficients (β) and their 95% confidence intervals were calculated. The level of significance was p < 0.05 (two-sided).

The demographic and clinical characteristics of the participants were summarized in Table 1. A total of 279 PD patients with a median age at assessment of 64.00 years old, median disease duration of 6.00 years, and median age of PD onset of 57.00 years were enrolled in our study, and 56.99% were males. There were no significant sex-specific differences in age, disease duration, age at onset, BMI, use of lipid-lowering medicines, H-Y staging, MDS-UPDRS III total scores, and LEED (Table 1). Males had more education years, higher MoCA scores, and lower HAMA and HAMD scores than females (Table 1). Subsequent analyses of the association between lipid profiles and motor performance therefore included MoCA and HAMA scores as covariates, as well as other demographic and clinical variables.

To explore the association of lipids with motor performance considering sex differences in lipid profiles, a total of 159 males and 120 females with PD were included and lipids were measured. The mean level of TG was 1.21 mmol/L, TC was 4.10 mmol/L, LDL-C was 2.44 mmol/L, HDL-C was 1.23 mmol/L, Apo-A1 was 1.35 g/L, and Apo-B was 0.86 g/L.

We compared lipid profiles between males and females with PD, as sex-specific differences in lipid profiles are often reported in healthy populations [16, 17] and a study showed higher TC and LDL-C levels associated with lower PD risk in males [5]. We observed significant differences between male and female participants in serum levels of TC (p < 0.001), LDL-C (p < 0.001), HDL-C (p = 0.001), Apo-A1 (p < 0.001), and Apo-B (p = 0.018) (Fig. 1). Such a difference was not found in serum TG levels (p > 0.05) (Fig. 1). Therefore, in order to accurately explore the effects of lipid profiles on motor performance in patients with PD, the sex-based analyses were considered necessary and were employed for further statistical analyses concerning TC, LDL-C, HDL-C, Apo-A1, and Apo-B. However, analysis of TG levels was conducted in males and females together.

Considering the missing information for MDS-UPDRS III subitem scores of 12 participants, we finally enrolled 267 PD participants in the following linear regression analysis.

The univariate linear regression model showed that lower serum TG levels were significantly associated with higher MDS-UPDRS III total scores, rigidity subscores, bradykinesia subscores, and gait/postural instability subscores in PD patients (p < 0.05) (Table 2). The multivariable linear regression models (models 1 and 2) showed that lower serum TG levels were significantly associated with higher MDS-UPDRS III total scores and gait/postural instability subscores (p < 0.05) (Table 2); no significant association was shown between TG levels and rigid subscores and bradykinesia subscores in the two models. Serum TG levels were not significantly associated with tremor subscores in either the univariate or multivariable linear regression model (p > 0.05) (Table 2).

The univariate and multivariable linear regression models (models 1 and 2) showed that serum TC levels were not significantly associated with motor performance in males or females with PD (p > 0.05) (Supplementary Table 1).

The univariate and multivariable linear regression models (models 1 and 2) showed that serum LDL-C levels were not significantly associated with motor performance in males or females with PD (p > 0.05) (Supplementary Table 2).

The univariate linear regression model showed that higher HDL-C levels were significantly associated with higher tremor subscores in males (p < 0.05), while only tendencies toward significant associations (P < 0.1) were found in model 1 and model 2 (Table 3). There were no significant associations between HDL-C levels and MDS-UPDRS III total scores, rigidity subscores, bradykinesia subscores, and gait/postural instability subscores in males (p > 0.05) (Table 3). The univariate and multivariable linear regression models (models 1 and 2) showed that serum HDL-C levels were not significantly associated with motor performance in females with PD (p > 0.05) (Table 3).

The univariate linear regression model showed that higher Apo-A1 levels were significantly associated with higher tremor subscores (p < 0.05), while only tendencies toward significant associations (p < 0.1) were found in model 1 and model 2 (Table 4). There were no significant association between Apo-A1 levels and MDS-UPDRS III total scores, rigidity subscores, bradykinesia subscores, and gait/postural instability subscores in males (p > 0.05) (Table 4). The univariate and multivariable linear regression models (models 1 and 2) showed that serum Apo-A1 levels were not significantly associated with motor performance in females with PD (p > 0.05) (Table 4).

The univariate linear regression model showed no significant association between Apo-B levels and motor performance in PD patients (p > 0.05), while the multivariable linear regression models (models 1 and 2) showed that Apo-B levels were significantly associated with gait/postural instability subscores in males with PD (p < 0.05) (Table 5).