Sleep disturbances such as decreased oxygen saturation may lead to neurocognitive dysfunction in patients with sickle cell disease (SCD), according to a study recently published in Sleep Medicine.

Specifically, nocturnal oxygen saturation (SpO2) seems to be independently related to verbal comprehension and working memory, which are characteristically diminished in these patients, as Tucker and the team reported.

To analyze this relation, a total of 27 patients previously diagnosed with SCD, aged 6 to 17 years, underwent neuropsychological evaluations utilizing the Wechsler Scales of Intelligence, Delis-Kaplan Executive Function System, Trail Making Test, Behavior Assessment for Children, Behavior Rating Inventory of Executive Function, and a number-letter sequencing test.

They also used parent-reported questionnaires to determine executive function outcomes and emotional and behavioral functions while assessing sleep disturbances with standardized polysomnography in all participants, collecting data on 4 specific parameters: apnea-hypopnea index, mean SpO2, total percentage of time spent below 90% oxygen saturation (pTST SpO2 <90%), and arousal index.

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Arguably the most impactful result was that, on average, for every unit decrease in mean nocturnal SpO2, verbal comprehension also decreased by 2.37 standard deviations. Previous publications differ on the exact causes of impaired verbal comprehension in patients with SCD, pointing out sleep-disordered breathing or decreased phonological processing as the main actors. Still, as with most cognitive processes, this skill requires logical, abstract, and generalization thinking, performed by the frontal lobe.

“Thus, the pathophysiological mechanism underlying the decline seen in verbal comprehension may be associated with decreased activation in the prefrontal cortex, which is known to be affected by nocturnal oxygen desaturation the most,” the authors explained.

Moreover, there was a 1% increase in pTST SpO2 <90%, translated into a 1.46 standard point decrease for working memory. This function shares considerable similarities with verbal comprehension, including the need for coordinated actions among multiple brain regions that yield the ability to hold and manipulate information in the mind.

Although these results could be expected, the clear characterization of inefficient cognitive functions and their relation with sleep parameters surely calls for further research on therapeutic options involving oxygen for this population.

“Overall, these findings identify the need for optimal nocturnal oxygen in youth with SCD, and sleep as a potential modifiable factor to be targeted by behavioral and pharmacological interventions to reduce neurocognitive deficits,” the authors concluded.


Tucker T, Alishlash A, Lebensburger J, et al. The association between sleep disturbances and neurocognitive function in pediatric sickle cell disease. Sleep Med. Published online May 26, 2022. doi:10.1016/j.sleep.2022.05.015