The Glymphatic System and Obesity: A Diffusion Tensor Imaging ALPS Study

Background: Obesity is a known risk factor for neurodegenerative diseases, potentially due to impaired clearance of brain waste through the glymphatic system. While the association between obesity and brain dysfunction has been widely studied in populations with neurological conditions, it remains unclear whether glymphatic system function is already reduced in neurologically healthy individuals with obesity. This study aimed to investigate whether glymphatic system function, measured via the diffusion tensor image (DTI) analysis along the perivascular space (DTI-ALPS) index, differs according to obesity status in neurologically healthy adults. Methods: We retrospectively analyzed brain DTI data from 62 neurologically healthy participants stratified into underweight (<18.5 kg/m²), normal weight (BMI ≥ 18.5 and <23.0 kg/m²), overweight (BMI ≥ 23.0 and <25.0 kg/m²), and obese (≥25.0 kg/m²) groups based on the World Health Organization Asia-Pacific body mass index (BMI) criteria. Group differences were examined using Mann-Whitney U tests and analysis of covariance, after adjusting for age. Results: Participants with obesity had significantly lower DTI-ALPS index values (1.262 ± 0.150) compared to those in the normal weight (1.405 ± 0.168, p = 0.048) and overweight (1.423 ± 0.195, p = 0.029) categories, even after adjusting for age. The DTI-ALPS index was also significantly reduced in participants with obesity compared to participants in the BMI < 25 kg/m² group (1.410 ± 0.176, p = 0.015). Conclusions: This study provides the first evidence that obesity is linked to reduced glymphatic system function, as reflected by lower DTI-ALPS index in neurologically healthy adults. These findings underscore the importance of maintaining a healthy body weight to preserve brain waste clearance mechanisms and may offer insights into early vulnerability to neurodegenerative changes.