Glymphatic system dysfunction in adult ADHD: Relationship to cognitive performance.

Objective: While attention-deficit/hyperactivity disorder (ADHD) persists into adulthood, the relationship between glymphatic system function and cognitive performance in adult ADHD remains unclear. This study investigated the association between glymphatic system markers and cognitive outcomes in adults with ADHD.

Methods: This case-control study includes 41 adults with ADHD and 108 age-matched healthy controls (HCs). Glymphatic function was evaluated using choroid plexus volume (CPV), diffusion tensor imaging along the perivascular space (DTI-ALPS) index and coupling between blood‑oxygen-level-dependent signals and cerebrospinal fluid signals (BOLD-CSF coupling). Cognitive performance was measured using standardized neuropsychological tests.

Results: Compared with HCs, adults with ADHD exhibited significantly lower bilateral and whole-brain ALPS indices (P < 0.05). Although CPV was increased in the ADHD group, this difference did not reach statistical significance, and no significant differences were observed in BOLD-CSF coupling between the two groups. Furthermore, whole-brain ALPS indices were positively associated with visual memory performance (r = 0.422, P = 0.005), an effect that was more pronounced in the right hemisphere (r = 0.458, P = 0.002).

Conclusions: The cross-sectional design limits causal inferences, and the effects of medication were not fully accounted for. Conclusions: These findings identify an association between glymphatic dysfunction and cognitive impairment in adults with ADHD. The observed correlation suggests that alterations in glymphatic function may underlie ADHD-related cognitive deficits. Targeting these pathways could provide novel therapeutic opportunities in the management of adult ADHD.