Mary J. Morrell, Donald W. McRobbie, Rebecca A. Quest, Andrew R.C. Cummin, Ramesh Ghiassi, Douglas R. Corfield 2003 Kathy Liu

Introduction What is obstructive sleep apnea (OSA)? -periodic breathing -episodic hypoxemia -repeated arousals from sleep -1-4% of middle-aged adults % of elders ( Bixler EO, Vgontzas AN, Lin T, et al.)

Introduction -Both hypoxia and sleep fragmentation independently result in cognitive deficits. -In rats, chronic exposure to intermittent hypoxia during sleep results in cellular damage within the CA1 region of the hippocampus ( Gozal D, Daniel JM, Dohaich GP. ) -Hippocampal cortex is sensitive to hypoxic damage -Hippocampus is closely associated with the neural processing of memory ( Maguire EA, Gadian DG, Johnsrude IS, et al.)

Hypothesis OSA is associated with changes in brain morphology; in particular, a focal loss of gray matter within the hippocampus and other cortical areas linked with cognitive function

Method Participants -7 right handed, male patients with newly diagnosed OSA (median, range: age 50, 28-65) -7 healthy, non-apneic male -all patients and controls had normal lung function -no patients had started continuous positive airway pressure treatment -body weight >130kg or girth measurement >152cm were excluded

Method Procedure -recruited from sleep clinic -an overnight home study during which breathing, O2 saturation, heart rate and body position were monitored -an apnea was defined as a >50% reduction in airflow for more than 10s -hypopnea : between 50%-75% reduction in airflow for more than 10s -median range of apnea hypopnea index (AHI)=28 events/h

Method -MR brain scan -Voxel-based morphormetry (VBM) -Normalisation: To account for normal differences in brain size and shape and in positions of the gyri, each brain image is resized and reshaped to fit a standardised brain template -Segmentation: each brain image is segmented into three compartments (cerebrospinal fluid, gray and white matter), based on the signal intensity of the MR image -Smoothing: To account for small scale differences in brain morphology

Result -significantly lower gray matter concentration in the OSA patients within the left hippocampus -No further significant focal gray matter differences were seen in the right hippocampus and in other brain regions -No difference in total gray matter volume between apneics and controls (mean ± SEM : ± vs ± )

Discussion -acute hypoxia produces both molecular and cellular neuronal damage -hippocampal neurons show increased sensitivity to low-O2 conditions and repetitive intermittent hypoxia reduces neuronal excitability in the CA1 region ( Gozal D, Daniel JM, Dohaich G P) -gray matter loss in patients results from the hypoxic insult -role of frequent arousals and the associated sleep fragmentation on any structural changes is less clear -cortical excitability is reduced following sleep deprivation ( Manganotti P, Palermo A, Patuzzo S, et al.)

Strength and limitation -moderate OSA is associated with focal gray matter loss in areas required for cognitive function -relatively small study size and relatively moderate AHI and hypoxaemia present in patient group -not able to relate the disease severity to the amount of gray matter loss -not correlated gray matter loss with indices of cognitive function

Further research -correlation of gray matter loss with cognitive function -whether treatment of the OSA could prevent the neuronal damage -loss of gray matter is the result of treatment?

Reference -Bixler EO, Vgontzas AN, Lin T, et al. Effects of age on sleep apnea in men: I. Prevanlence and severity. Am J Pespir Crit Care Med 1998; 157: Gozal D, Daniel JM, Dohaich GP. Behavioural and anatomical correlates of chronic episodic hypoxia during sleep in the rat. J Neurosci 2001; 21: Maguire EA, Gadian DG, Johnsrude IS, et al. A voxel-based morphometric study ofagein gin 465 normal adult human brains. Neuroimage 2001; 97: Manganotti P, Palermo A, Patuzzo S, et al. Decrease in motor cortical excitability in human subjects after sleep deprivation. Neurosci Lett 2001; 304: 153-6

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