A new study published in the Journal of Affective Disorders has found that adults with attention-deficit/hyperactivity disorder (ADHD) show signs of glymphatic system dysfunction, which may be related to their cognitive difficulties. The findings suggest that disruptions in the brain’s waste clearance system could help explain some of the persistent memory and attention problems seen in adults with the condition.
ADHD is a common neurodevelopmental disorder marked by symptoms of inattention, impulsivity, and hyperactivity. While it is often diagnosed in childhood, many people continue to experience symptoms well into adulthood. In adults, ADHD can interfere with work, relationships, and daily functioning, and is often accompanied by cognitive issues such as forgetfulness and difficulty sustaining focus. Although behavioral symptoms are widely studied, the biological mechanisms that underlie adult ADHD are less understood.
One area of growing interest among scientists is the glymphatic system—a network that helps clear waste products from the brain. This system operates mainly during deep sleep and uses cerebrospinal fluid to flush out harmful substances. Problems with glymphatic function have been linked to other brain disorders, such as Alzheimer’s disease. However, little is known about its role in ADHD, especially in adults. The researchers behind this study wanted to explore whether changes in glymphatic function could help explain the cognitive impairments associated with the condition.
To do this, the team analyzed brain imaging and cognitive data from 41 adults diagnosed with ADHD and compared them to 108 healthy adults. The data came from the University of California, Los Angeles Consortium for Neuropsychiatric Phenomic LA5c Study and included both structural and functional magnetic resonance imaging (MRI) scans, along with results from several cognitive tests. The researchers used advanced neuroimaging techniques to assess three indicators of glymphatic function: the volume of the choroid plexus (a part of the brain that produces cerebrospinal fluid), a measure known as the ALPS index (which reflects how well fluid moves along blood vessels in the brain), and the strength of the connection between brain activity and cerebrospinal fluid flow (called gBOLD-CSF coupling).
The participants also completed a range of assessments, including the Adult ADHD Self-Report Scale to measure ADHD symptoms, and standardized tests to evaluate memory, attention, and verbal learning. These included the California Verbal Learning Test and the Wechsler Memory Scale.
The results showed that adults with ADHD had lower ALPS index scores than healthy individuals, suggesting reduced glymphatic activity. This difference was observed across both hemispheres of the brain. The decrease in ALPS scores was linked to reduced fluid movement along specific fiber pathways in the brain, particularly those involved in communication between regions. These findings point to a possible impairment in how effectively the brain is able to clear waste.
Although the volume of the choroid plexus tended to be higher in the ADHD group, this difference did not reach statistical significance. This may suggest a potential compensatory response or a marker of altered cerebrospinal fluid dynamics, but more research is needed to draw firm conclusions. Likewise, there were no significant differences between the ADHD and control groups in terms of gBOLD-CSF coupling, which reflects functional synchronization between brain activity and fluid flow. This suggests that while structural glymphatic changes may be present, the overall coordination between brain and fluid activity remains intact in adults with ADHD.
Importantly, the researchers found that lower ALPS index scores were associated with poorer performance on memory tasks, including visual reproduction and delayed recognition. These correlations were stronger in the right hemisphere. The ALPS index also showed links with higher scores on obsessive-compulsive symptoms in participants with ADHD, suggesting a broader relationship between glymphatic function and psychiatric features.
In healthy participants, higher ALPS scores were also associated with better memory performance, suggesting that glymphatic activity may play a broader role in supporting cognitive health across individuals, not just those with ADHD.
These findings open up the possibility that glymphatic dysfunction contributes to the cognitive symptoms experienced by adults with ADHD. The researchers propose that impaired waste clearance could lead to the buildup of metabolic byproducts that interfere with brain signaling, particularly in pathways involving dopamine and norepinephrine. These neurotransmitters are already known to play a role in attention, motivation, and reward processing—all areas often affected in ADHD.
Another possible explanation is that impaired glymphatic function may contribute to low-grade inflammation in the brain, which has been increasingly recognized in ADHD research. Inflammation can disrupt brain development and affect how neurons communicate. The researchers also point out that sleep problems, which are common in ADHD, may worsen glymphatic dysfunction, since this system operates most effectively during deep sleep.
On a cellular level, the authors suggest that astrocytes—supportive brain cells that help regulate the glymphatic system—may play an important role. Astrocytes help manage fluid flow through channels called aquaporins and also influence how brain circuits develop. Dysfunction in these cells could create a cascade of problems affecting both waste clearance and neural communication.
While this study is one of the first to examine glymphatic function in adult ADHD, it has several limitations. Because the data are cross-sectional, the researchers cannot determine whether glymphatic dysfunction causes cognitive problems or results from them. Longitudinal studies are needed to better understand the direction of this relationship. The relatively small sample size also limits the generalizability of the findings, and future research should aim to replicate these results in larger and more diverse groups.
Despite these limitations, the study adds an important piece to the puzzle of ADHD. It suggests that biological systems beyond neurotransmitter signaling—such as waste clearance—may play a meaningful role in the disorder’s development and persistence. These insights could eventually lead to new therapeutic strategies. For example, improving sleep quality, promoting regular physical activity, or reducing brain inflammation could support glymphatic function and potentially ease cognitive symptoms in adults with ADHD.
The study, “Glymphatic system dysfunction in adult ADHD: Relationship to cognitive performance,” was authored by Yan Fang, Juan Peng, Tiantian Chu, Feng Gao, Fei Xiong, and Ye Tu.
