Association between body mass index and glymphatic function using diffusion tensor image-along the perivascular space (DTI-ALPS) in patients with Parkinson's disease

Abstract

Background: Obesity is considered a risk factor for the development of several neurodegenerative diseases, including Parkinson's disease (PD). Recent studies have revealed that glymphatic function is compromised in PD patients. This study aims to investigate the impact of different body mass index (BMI) statuses on glymphatic system function in PD patients using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method.

Methods: This study used a cross-sectional study design. A total of 145 PD patients were retrospectively enrolled in Parkinson's Progression Markers Initiative (PPMI) from 2010-2013. Eligibility criteria included diagnosis of PD based on PPMI criteria. Diffusion tensor image (DTI) scans (diffusion gradient =64, b-value =1,000 s/mm², slice thickness =2 mm) were acquired, and the analysis along the perivascular space (ALPS) index of each subject was calculated. The patient cohort was categorized into three groups based on BMI: normal weight (N=49), overweight (N=69), and obese (N=27). The difference in ALPS index among groups was performed by one-way analysis of variance (ANOVA). Partial correlation analysis was used to observe the relationship between ALPS index, BMI status, and demographics. Spearman's rank correlation coefficient and multivariable linear regression analyses were used to identify factors associated with ALPS index.

Results: PD patients with higher BMI exhibited a reduced ALPS index (normal weight > overweight > obese), and the ALPS index for patients with obesity was statistically significantly lower than that for patients with normal weight (P<0.001). After adjusting for age, sex, years of education, handedness, and disease duration, a significant negative correlation between the ALPS index and BMI was observed in the PD patients (R=-0.275, P<0.001). Furthermore, a negative correlation between the ALPS index and the severity of motor symptoms was identified in the subgroup of overweight (R=-0.318, P=0.01), rather than in the normal weight and obese groups.

Conclusions: High BMI has a negative impact on the glymphatic function in PD patients, suggesting that weight control may have clinical relevance in the management of PD patients.

Keywords: Body mass index (BMI); Parkinson’s disease (PD); diffusion tensor imaging; glymphatic system.

Figure 1

Flow diagram of the study selection in PPMI study. PD, Parkinson’s disease; DTI, diffusion tensor imaging; PPMI, Parkinson’s Progression Markers Initiative, CSF, cerebrospinal fluid, BMI, body mass index.

Figure 2

Violin plot showing the comparison of the ALPS index among the PD subjects with normal weight, overweight and obese groups. The ALPS index of the obese group was significantly lower than that in the normal weight groups. Data were represented as mean ± standard deviation, P<0.0167 (one-way analysis of variance followed by Bonferroni post-hoc). ALPS, analysis along the perivascular space; PD, Parkinson’s disease.

Figure 3

Spearman’s correlation matrix depicting the relationships between the ALPS index, age, education, disease duration, BMI, MoCA Score, MDS-UPDRS-III total score and CSF biomarkers. ALPS, analysis along the perivascular space; BMI, body mass index; MoCA, Montreal Cognitive Assessment; MDS-UPDRS-III, Movement Disorders Society-sponsored Unified Parkinson’s Disease Rating Scale-Part III; CSF, cerebrospinal fluid; p-tau, phospho-tau.

Figure 4

Associations between ALPS index and BMI in individuals with PD and its subgroups. Partial correlation test indicates a negative correlation between ALPS index and BMI in overall the PD groups (A), whereas no significant differences were observed in PD subgroups with different BMI statuses. (B) Normal weight; (C) overweight; (D) obese. ALPS, analysis along the perivascular space; BMI, body mass index; PD, Parkinson’s disease.

Figure 5

Associations between ALPS index and MDS-UPDRS-III total score in individuals with PD and subgroups. Partial correlation test indicates a negative correlation between ALPS index and BMI in the PD with overweight subjects (C), whereas there was no significant difference in PD groups and PD with normal weight and obese groups (A,B,D). MDS-UPDRS-III, Movement Disorders Society-sponsored Unified Parkinson’s Disease Rating Scale-Part III; ALPS, analysis along the perivascular space; BMI, body mass index; PD, Parkinson’s disease.