Reduced Diffusivity along Perivascular Spaces on MR Imaging Associated with Younger Age of First Use and Cognitive Impairment in Recreational Marijuana Users

Abstract

BACKGROUND AND PURPOSE:The impairment of the glymphatic system, a perivascular network crucial for brain waste clearance, has been linked to cognitive impairment, potentially attributed to the accumulation of brain waste. Although marijuana use has been associated with poorer cognitive performance, particularly in adolescents, its influence on the glymphatic system remains unexplored. This study evaluated the influence of the age of first marijuana use and the total number of lifetime uses on the glymphatic system, measured using the index of diffusion tensor imaging along the perivascular space (DTI-ALPS). Furthermore, we explored the correlation between glymphatic clearance and cognitive performance among marijuana users. MATERIALS AND METHODS:In this study, 125 individuals who reported using marijuana at least once in their lifetime (43 men; mean age, 28.60  3.84 years) and 125 individuals with zero lifetime cannabis use (nonusers; 44 men; mean age, 28.82  3.56 years) were assessed. ALPS indices of all study participants were calculated using 3T diffusion MRI data (b = 1,000 s/mm 2 ). RESULTS:After adjusting for age, sex, education years, Pittsburgh Sleep Quality Index, alcohol use, tobacco use, and intracranial volume, our analysis using a univariate general linear model revealed no significant difference in the ALPS index among nonusers and marijuana users with different ages of first use or various frequencies of lifetime usage. However, in marijuana users, multiple linear regression analyses showed associations between a lower ALPS index and earlier age of first marijuana use (standardized , 0.20; P = 0.041), lower accuracy in the working memory 0-back task (standardized , 0.20; P = 0.042), and fewer correct responses in the fluid intelligence test (standardized , 0.19; P = 0.045). CONCLUSIONS:This study shows the potential use of DTI-ALPS as a noninvasive indirect indicator of the glymphatic clearance in young adults. Our findings show novel adverse effects of younger age at first use of marijuana on glymphatic system function, which is associated with impaired working memory and fluid intelligence. Gaining insights into alterations in glymphatic function following marijuana use could initiate novel strategies to reduce risk of cognitive impairment.