Hypnotic-associated falls across the diurnal cycle: Pharmacokinetic signal or delirium rhythm?

Insomnia disorder (ID) and obstructive sleep apnea (OSA) are sleep diseases with the highest prevalence rates and significantly contribute to cognitive impairment, mood disorders, and daytime fatigue. OSA exhibits the typical features of snoring and choking while sleeping at night, resulting in cortical arousal, hypopnea, apnea, and the declined blood oxygen saturation. On the other hand, ID is associated with the difficulty in falling or being asleep and waking up early in the morning. OSA and ID often coexist, and the comorbidity of insomnia and sleep apnea (COMISA) may occur in 30–50% of patients.A previous study reported that COMISA had a higher incidence than ID or OSA. Additionally, individuals with COMISA experience a greater incidence of cognitive and behavioral impairments and psychiatric disorders than those with only ID or OSA. Although COMISA has significant cognitive and mood effects, our understanding of the neuroanatomical alterations associated with this comorbidity is limited. Several studies have investigated cortical thickness (CT) in patients suffering from OSA and ID by conducting high-resolution magnetic resonance imaging (MRI). Some brain regions associated with OSA, including the precentral and postcentral gyri, superior temporal gyrus, left dorsal posterior insula, and right inferior parietal gyrus, show CT alterations. Researchers have postulated that a decrease in CT might signify atrophy caused by long-term damage, such as the loss of neurons and supporting glial cells due to repeated intermittent hypoxic episodes, leading to working memory deficits, motor dysfunction, or reduction in speech encoding. Moreover, Chokesuwattanaskul et al. classified participants into mild or severe hypoxia based on hypoxia parameters, such as the lowest oxygen saturation, oxygen desaturation index, and total sleep time < 90% oxygen saturation, and reported cortical thinning in right inferior parietal and frontal gyri of severe desaturation group as well as in superior parietal gyrus of high oxygen desaturation index group. When considering patients with ID, however, a degree of inconsistency was found in CT changes. CT was found to increase and decrease among ID patients. Although several structural neuroimaging studies have investigated changes in CT in individuals with ID or OSA alone, CT changes specific to COMISA are limited. We note that the same cohort has been previously used to examine gray matter volume (GMV) alterations in COMISA; the present study extends this work by focusing on cortical thickness (CT), a distinct morphometric measure that provides different biological information. A growing body of literature indicates that CT and GMV reflect complementary aspects of brain morphology: genetic studies have shown that cortical thickness and surface area are genetically independent, methodologically CT is less confounded by head size than GMV, and disease-based studies have demonstrated that these two metrics exhibit distinct regional vulnerability patterns. Thus, analyzing CT in the same cohort can yield novel insights into COMISA-related brain pathology that are not reducible to previous GMV findings. Therefore, our current study used surface-based morphometry (SBM) to compute whole-brain cortical thickness (CT) at the voxel-wise level and compared CT alterations between patients with COMISA and healthy controls (HCs), all of whom completed measures of respiration, sleep, cognition, and mood. Additionally, we further explored the CT alterations at different severity stages of patients with COMISA and the associations of respiration, sleep, cognition, and mood measures.