Changes in Neurocognitive Architecture in Patients with Obstructive Sleep Apnea Treated with Continuous Positive Airway Pressure

Abstract

BackgroundObstructive sleep apnea (OSA) is a chronic, multisystem disorder that has a bidirectional relationship with several major neurological disorders, including Alzheimer's dementia. Treatment with Continuous Positive Airway Pressure (CPAP) offers some protection from the effects of OSA, although it is still unclear which populations should be targeted, for how long, and what the effects of treatment are on different organ systems. We investigated whether cognitive improvements can be achieved as early as one month into CPAP treatment in patients with OSA.Methods55 patients (mean (SD) age: 47.6 (11.1) years) with newly diagnosed moderate–severe OSA (Oxygen Desaturation Index: 36.6 (25.2) events/hour; Epworth sleepiness score (ESS): 12.8 (4.9)) and 35 matched healthy volunteers were studied. All participants underwent neurocognitive testing, neuroimaging and polysomnography. Patients were randomized into parallel groups: CPAP with best supportive care (BSC), or BSC alone for one month, after which they were re-tested.FindingsOne month of CPAP with BSC resulted in a hypertrophic trend in the right thalamus [mean difference (%): 4.04, 95% CI: 1.47 to 6.61], which was absent in the BSC group [− 2.29, 95% CI: − 4.34 to − 0.24]. Significant improvement was also recorded in ESS, in the CPAP plus BSC group, following treatment [mean difference (%): − 27.97, 95% CI: − 36.75 to − 19.19 vs 2.46, 95% CI: − 5.23 to 10.15; P = 0.012], correlated to neuroplastic changes in brainstem (r = − 0.37; P = 0.05), and improvements in delayed logical memory scores [57.20, 95% CI: 42.94 to 71.46 vs 23.41, 95% CI: 17.17 to 29.65; P = 0.037].InterpretationOne month of CPAP treatment can lead to adaptive alterations in the neurocognitive architecture that underlies the reduced sleepiness, and improved verbal episodic memory in patients with OSA. We propose that partial neural recovery occurs during short periods of treatment with CPAP.

Lessons from randomised controlled trials of continuous positive airways pressure therapy in the prevention of cardiovascular morbidity and mortality

“…For example, in patients with established cardiovascular disease, there may be a limited degree of reversibility, similar to some of the data from parallel studies on the effect of OSA on the central nervous system (18,19). It may therefore be expected that mortality and morbidity would be equally high in both groups, and CPAP may provide limited benefit.…”

Emerging co-morbidities of obstructive sleep apnea: cognition, kidney disease, and cancer

“…The observed thalamocortical changes were associated with changes in bilateral hippocampi and cerebellar cortices (13). These data suggest that a relatively short period of CPAP treatment may allow rudimentary neuroplastic changes to occur within targeted brain structures of patients with moderate to severe Figure 4 Schematic presentation of the neuroarchitecture behind working memory maintenance processes that might be implicated in improved daytime somnolence and verbal episodic memory by the CPAP treatment (13). Distributed nature of processes and representations involved to solve working-memory tasks is shown, with thalamus (central structure) acting as a functional interface between arousal and attentional regulation.…”

“…They showed that 3 months of CPAP treatment was associated with a significant increase in grey matter volume in the bilateral hippocampus and frontal structures, which correlated with an improvement in executive function, memory and attention (12). Similarly, in a recent study that used randomised controlled design, one month of CPAP treatment resulted in a partial recovery of episodic and working-memory capacity ( Figure 4) (13). The observed thalamocortical changes were associated with changes in bilateral hippocampi and cerebellar cortices (13).…”

“…Similarly, in a recent study that used randomised controlled design, one month of CPAP treatment resulted in a partial recovery of episodic and working-memory capacity ( Figure 4) (13). The observed thalamocortical changes were associated with changes in bilateral hippocampi and cerebellar cortices (13). These data suggest that a relatively short period of CPAP treatment may allow rudimentary neuroplastic changes to occur within targeted brain structures of patients with moderate to severe Figure 4 Schematic presentation of the neuroarchitecture behind working memory maintenance processes that might be implicated in improved daytime somnolence and verbal episodic memory by the CPAP treatment (13).…”

“…Some of these impairments have been associated with corresponding structural changes (9,10). Continuous positive airway pressure (CPAP)-still the mainstay of OSA treatmenthas been shown to at least partially reverse some of the cognitive impairments and associated neuroanatomical changes (8,(11)(12)(13).…”