MRIs of healthy adolescents who experienced poor sleep quality, particularly in the NREM or slow-wave sleep stages, tended to have larger perivascular spaces, a factor associated with cognitive decline, according to an abstract presented in November at the Child Neurology Society annual meeting in San Diego. Neurologists said this research could open the door to looking at the impact of poor sleep quality on both adolescent and long-term health issues.
Researchers said the finding shows that a non-invasive, structural, and longitudinally trackable marker of glymphatic functions could help determine if impairments in NREM sleep quality impact brain health not only in people with neurodegenerative diseases or aging brains but also in healthy adolescents. But they cautioned that the data was collected after a single night's sleep, and longer studies will be needed.
“We suspect that everyone sits on their own perivascular growth trajectory that is influenced by both physiologic and pathophysiologic factors, and in turn influences their ability to clear cerebral waste as well as engage in other important glymphatic functions. These results suggest that sleep during adolescence—something that can be targeted and modified—may be one of these factors," said Seva G. Khambadkone, MD, PhD, lead author of the study and a child neurology resident at Oregon Health & Science University.
“A lot of work remains to be done, and we have a lot of questions, but I think one takeaway is that maybe one day we will start thinking about pediatric glymphatic health in a similar way that we think about childhood obesity."
The glymphatic system is primarily active during NREM sleep and is critical for clearing waste produced by the brain, sort of like a brain sewage system, said Dr. Khambadkone. Although most research has focused on older adults, glymphatic clearance is established early in life and perivascular spaces—the network through which glymphatic clearance occurs—can be seen on pediatric MRIs, she added.
The new study focused on the relationship between MRI-visible perivascular space (MV-PVS) volume and polysomnographic (PSG) measures of sleep in a healthy pediatric population, ages 12 to 21 years. The analysis included data from 111 participants from the sleep arm of the National Consortium on Alcohol and Neurodevelopment in Adolescence, a multisite, cohort-sequential, longitudinal study. Participants had a mean age of 15.3, and 47 were female. They underwent PSG studies and brain MRIs and were analyzed according to age, sex, body-mass index, and study site.
The study found that male participants had a “significantly" greater mean MV-PVS volume than females (7.57 +/- 1.22 vs. 6.72 +/- 1.22, p<0.001). MV-PVS volume in the white matter was negatively associated with delta EEG power in NREM2 sleep, and MV-PVS volume in the basal ganglia was negatively associated with delta EEG power in NREM3 sleep. Researchers did not observe any associations between MV-PVS volumes and PSG measures of wake after sleep onset, sleep efficiency, or time spent in NREM2 or NREM3 sleep.
The results highlighted the “potential physiologic relevance of MV-PVS in healthy adolescents and young adults," the study authors wrote. Dr. Khambadkone said studying healthy adolescents will allow them to research implications for neurologic impacts. One of the next steps is to address youth who have had a traumatic brain injury—which often is associated with severe sleep disturbances—looking at the relationship between TBI, sleep, and perivascular spaces.
“While a huge focus of this field has been in neurodegeneration and aging, we can't stop thinking about what role this system could have in mediating neurodevelopment and neurologic health and function across the lifespan, and how we can intervene to both mitigate risk and promote resilience—for example, by targeting sleep health," Dr. Khambadkone said.
Temitayo Oyegbile-Chidi, MD, PhD, FAAN, FAES, FANA, an associate professor of neurology who is certified in pediatric neurology, epilepsy, and sleep medicine at the University of California, Davis, said researchers are just beginning to understand the role of sleep in neurologic disorders. She was excited that the study focused on adolescent brains, which opened possibilities to study how sleep impacts development.
“This was one of the first studies investigating the role of sleep-related glymphatic function and neurodevelopmental brain health in an adolescent population. Prioritizing sleep to optimize daytime function as well as short-term and long-term neurologic health is crucial in the pediatric population and not just in older adults," said Dr. Oyegbile-Chidi, noting that it would be interesting to further investigate the impact of glymphatic function in sleep on neurologic disorders of childhood, such as autism, epilepsy, and attention deficit disorders.
“Traditionally, it has been believed that glymphatic dysfunction related to cumulative poor sleep is a problem of older adults and is associated with the development of cognitive impairment including dementias," she added. “But this study indicates that glymphatic dysfunction can be observed in very early developmental stages. Future studies are necessary to clearly characterize this dysfunction in the pediatric population and the long-term consequences. Regardless, this study adds to the accumulating evidence that sleep is very important for optimal brain development and brain health in the pediatric population."
https://journals.lww.com/neurotodayonline/blog/NeurologyTodayConferenceReportersCNSAnnualMeeting/pages/post.aspx?PostID=63&utm_source
Child Neurology Society Abstract PL1-7: Khambadkone SG, Yamamoto EA, Koike S, et al. Delta power during sleep is associated with MRI-visible perivascular space volume in adolescents and young adults.
OBJECTIVE: Enlarged, MRI-visible perivascular spaces (MV-PVS) are putative markers of impaired glymphatic function, and are increasingly recognized in the general pediatric population. The significance of MV-PVS in the developing brain remains unknown. In adults, slow-wave sleep has been shown to mediate glymphatic function, and poor sleep quality is associated with larger MV-PVS volume. The aim of this study was to determine the relationship between MV-PVS volume and polysomnographic (PSG) and electroencephalographic (EEG) measures of sleep in a healthy pediatric population. METHODS: Data were analyzed from 111 participants (age range:12-21 years of age, mean: 15.32.2 years, 47 female) enrolled in a sleep arm of the National Consortium on Alcohol and Neurodevelopment in Adolescence, a multisite, cohort-sequential, longitudinal study. Participants underwent PSG studies and brain MRI scans at study entry. MV-PVS volume/white matter (WM; mm3/cm3) was quantified using an automated detection algorithm. Associations between MV-PVS volume and PSG and EEG measures (log transformed) were analyzed by linear regression including age, sex, BMI, and study site as covariates. RESULTS: Males had significantly greater mean MV-PVS volume/WM than females (7.571.22 vs 6.721.22, p<0.001). MV-PVS volume/WM was negatively associated with delta EEG power in Stage N2 sleep (β=-0.50, SE=0.23, p=0.035), but not in Stage N3 sleep. There were no associations observed between MV-PVS volume/WM and PSG measures of wake after sleep onset, sleep efficiency, or time spent in N2 or N3 sleep. CONCLUSIONS: Lower delta power in N2 sleep was associated with larger MV-PVS volume, highlighting potential physiologic relevance of MV-PVS in healthy adolescents and young adults.
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