Elsevier

Sleep Medicine

Volume 5, Issue 6, November 2004, Pages 593-596
Sleep Medicine

Brief communication
Hippocampal area metabolites relate to severity and cognitive function in obstructive sleep apnea

https://doi.org/10.1016/j.sleep.2004.08.004Get rights and content

Abstract

Background and purpose: Obstructive sleep apnea (OSA) is associated with intermittent hypoxia and cognitive decrements. As the hippocampus is particularly susceptible to hypoxia, we hypothesized that it may show biochemical abnormalities, and they may relate to apnea severity.

Patients and methods: Eight males with OSA and five age-matched controls underwent neurocognitive testing before and after polysomnography and proton magnetic resonance spectra were obtained from the left hippocampal area of all subjects.

Results: In the left hippocampal area, N-acetyl-containing/creatine-containing compounds was significantly increased in OSA (P=0.04). Inspection of these compounds with respect to the water resonance indicated that this was most likely due to a decrease in creatine-containing compounds rather than any change in N-acetyl-containing compounds. Lower levels of hippocampal creatine-containing compounds were correlated with worse OSA severity and neurocognitive performance.

Conclusions: We suggest the changes in creatine levels in the hippocampal area represent adjustments to brain bioenergetics, similar to those seen in ischemic preconditioning, and may reflect the different susceptibility of these tissues to hypoxic damage in OSA.

Introduction

Obstructive sleep apnea (OSA) is characterized by both repetitive asphyxia and sleep fragmentation leading to neurocognitive decrements and vascular disease [1]. There are varying levels of daytime dysfunction reported in patients with OSA [1], including memory impairment. The hippocampus is extremely vulnerable to intermittent hypoxic insult in animal models [2]. Recently, hippocampal grey matter volumes were decreased in association with OSA [3], suggesting this vulnerability translates to humans.

To examine this further, we studied the hippocampal area of eight subjects with OSA and five controls using 1H magnetic resonance spectroscopy (MRS) and a neurocognitive test battery, immediately following overnight polysomnography (PSG).

Section snippets

Methods

This study complied with NHMRC guidelines on human research and was approved by institutional Ethics Committees. Informed consent was obtained from all participants. Eight OSA subjects (mean age 48.7 years (range 41.1–56.4 years)) were recruited from sleep clinics at St Vincent's Clinic and Royal North Shore Hospitals in Sydney, Australia. Selection criteria included both a respiratory disturbance index of >15 and a minimum oxygen desaturation of ≤90% (Sa02<90%). Five control subjects (mean age

Results

There were clear differences between OSA subjects and controls in all sleep and breathing variables (Table 1). BMI, but not age, was significantly different between the OSA and control groups.

Discussion

Using 1H MR spectroscopy we observed a major change in brain neurochemistry. The Cre resonance decreased in the hippocampal area in diagnosed OSA subjects compared with control subjects, and was associated with worsening neurocognitive performance. It is perhaps not surprising that the Cre resonance should be sensitive to intermittent hypoxia. Creatine plays a pivotal role in brain energy homeostasis and acts in concert with multiple ATP-producing and requiring reactions as a buffer for

Acknowledgements

The authors acknowledge the expert assistance of Dr Bodgan Chapman and would like to thank Dr James Linklater in the assessment and reading of the MRI scans to exclude cerebral abnormalities. This work was supported by the Australian NHMRC (No. 253792 and Fellowships to CR and RRG). The MRUI software package was kindly provided by the participants of the EU Network programmes: Human Capital and Mobility, CHRX-CT94-0432 and Training and Mobility of Researchers, ERB-FMRX-CT970160.

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1

Current address: Flinders Medical Centre, South Australia.

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