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

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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