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

2003

Kathy Liu

IntroductionWhat is obstructive sleep apnea (OSA)?-periodic breathing-episodic hypoxemia-repeated arousals from sleep-1-4% of middle-aged adults-24-30% 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

MethodParticipants-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

MethodProcedure-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 : 0.914 ± 0.012 vs. 0.913 ± 0.0131)

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 GP)

-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: 144-8

-Gozal D, Daniel JM, Dohaich GP. Behavioural and anatomical correlates of chronic

episodic hypoxia during sleep in the rat. J Neurosci 2001; 21: 2442-50

-Maguire EA, Gadian DG, Johnsrude IS, et al. A voxel-based morphometric study

ofagein gin 465 normal adult human brains. Neuroimage 2001; 97: 4398-403

-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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