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

Abstract

Background: Obstructive 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.

Methods: 55 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.

Findings: One 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].

Interpretation: One 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.

Keywords: Cognition; Continuous Positive Airway Pressure; Neuroimaging; Obstructive sleep apnea.

Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1

CONSORT diagram.

Fig. 2

Dendrograms depict relationships between structural changes in brain volumes following one month of intervention with the Continuous Positive Airway Pressure or Best Supportive Care treatment. Dendrograms were constructed using the results of Hierarchical Cluster Analysis (HCA) of the differential ∆ structural changes, using Average Linkage with squared Euclidean distance as a measure of distance (x-axis values). HCA resulted in the formation of clusters that were iteratively joined in a descending order of similarity. Resulting dendrograms show different patterns of neuroanatomical changes in patients with OSA following the interventions with BSC alone (N = 27) from those resulting post CPAP with BSC (N = 28) treatment. The HCA findings also suggest that the thalamic alterations (arrows) in the CPAP group are closely linked to wider core neurocircuitry adaptations (pink boxes).

Fig. 3

Significant structural change in OSA patients Pre and Post CPAP treatment. The first row (Pre-) shows neuroanatomical structures that were noted as hypotrophic in OSA patients (N = 55) before any intervention, by comparison to matched healthy volunteers (N = 35); bilateral globus pallidi, left hippocampi and mid posterior section of corpus callosum. The second row (Post-) depicts hypertrophic changes noted in bilateral thalami following one month of treatment with CPAP; the longitudinal structural changes were calculated by normalization to the individual baseline volumes (refer to the equation).

Fig. 4

Neuroplastic structural changes following one month of intervention with the Continuous Positive Airway Pressure or Best Supportive Care treatment. Potential strengthening in interregional connectivity between the non-dominant thalamus with hippocampus and (or) cerebellar cortex in OSA patients was noted only in CPAP treated group (first row). In addition, in the same group of patients, improvement in sleepiness (as shown by the ESS), was strongly positively correlated to changes occurring in brainstem during this period (second row).

Fig. 5

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. Distributed nature of processes and representations involved to solve working-memory tasks is shown (McNab and Klingberg, 2008, Eriksson et al., 2015), with thalamus (central structure) acting as a functional interface between arousal and attentional regulation (Schiff, 2008). The hippocampus (elongated green), is the structure most frequently reported affected by neuroimaging in OSA (Rosenzweig et al., 2015, Rosenzweig et al., 2013b), here it is proposed to bind aspects of working and episodic memory (Eriksson et al., 2015, Axmacher et al., 2010). The list of cognitive tests used in our study to investigate impact of CPAP treatment on associated cognitive domains is also depicted. CPAP treatment leads to improvement in verbal episodic memory (green box), which may be due to the interplay of the cascade of gradual changes in the semantic and verbal working memory. In addition, CPAP leads to the improvement of excessive daytime somnolence (yellow box), which in turn appears to be significantly, correlated to ensuing brainstem alterations. Our results also suggest that comparable subjective sleepiness has significantly less impact on the attention and maintenance of working memory capacity in patients treated with CPAP. Abbreviations: CPAP: Continuous Positive Airway Pressure; BSC: best supportive care; LTM: long term memory; ESS: Epworth sleepiness scale.