Undiagnosed sleep-related breathing disorders are associated with focal brainstem atrophy in the elderly

Sébastien Celle, Roland Peyron, Isabelle Faillenot, Vincent Pichot, Majed Alabdullah, Jean-Michel Gaspoz, Bernard Laurent, Jean-Claude Barthélémy, Frédéric Roche, Sébastien Celle, Roland Peyron, Isabelle Faillenot, Vincent Pichot, Majed Alabdullah, Jean-Michel Gaspoz, Bernard Laurent, Jean-Claude Barthélémy, Frédéric Roche

Abstract

Background: Sleep-related breathing disorders (SRBDs) affect as many as 40% of elderly people. The association of SRBDs with structural brain abnormalities remains unclear. In this observational study, we evaluated gray matter changes in the brain associated with sleep abnormalities in volunteers and their relationship with the severity of SRBDs.

Methods: One hundred fifty two healthy subjects aged 66.0 +/- 0.6 years-old underwent tridimensional brain MRI and nocturnal polygraphic recording during which apnea/hypopnea index (AHI) and the oxyhemoglobin desaturation index (ODI) were measured. Using voxel-based morphometry, we investigated the presence of gray matter abnormalities in association with AHI and ODI.

Findings: Seventy-six subjects (50%) had SRBDs defined by an AHI > or = to 15 and 25 subjects (16%) SRBDs defined by an ODI > or = 15, in the absence of systematic excessive daytime sleepiness. A significant symmetrical loss of gray matter in the intermediate reticular zone of the bulbopontine area was found to correlate with both AHI and ODI (P < 0.05 corrected for multiple comparisons for cluster significance).

Interpretation: This gray matter volume decrease in brain regions involved in breathing/autonomic functions, as well as their correlation with the severity of the disorder, suggests a pathophysiological link between structural changes and SRBDs.

Copyright 2009 Wiley-Liss, Inc

Figures

Figure 1
Figure 1
Correlations between gray matter decrease and SRBDs using AHI criteria. An inverse correlation between gray matter volume and apnea hypopnea index (AHI) is present in the brainstem and in the cerebellum. Results are displayed with a P < 0.05 threshold, corrected for multiple comparisons, at the cluster level. Results are presented in neurological convention (i.e., left side of the brain is on the left side of the figure). (a) Projections map (SPM2) showing the correlation between brainstem and SRBDs. No correlation can be seen outside the brainstem and cerebellum. (b) Maximum of correlation between gray matter loss and AHI. Note that the cluster is extended in the upper medulla/inferior pontine region, close to the ventricular surface, bilaterally, almost symmetrically; in a localization consistent with the intermediate reticular zone of the bulbopontine area (see stereotaxic coordinates (MNI) in Table II). The clusters are projected onto the specific template performed for this study from the 61 averaged subjects with normal MRI.
Figure 2
Figure 2
Group analysis: Subjects with severe SRBDs (ODI ≥ 15) versus non‐SRBDs (ODI P < 0.05 threshold, corrected for multiple comparisons, at the cluster level (Table II). Gray matter loss in the group of subjects with SRBDs compared to those without SRBDs concerned the middle/inferior part of the lower pontine/upper medulla area. Results are presented in neurological convention (i.e., left side of the brain is on the left side of the figure). (a) Projections map (SPM2) showing a gray matter decrease only in the brainstem. (b) Maximum of correlation between gray matter loss and ODI. Note that the cluster is extended in the upper medulla/inferior pontine region, close to the ventricular surface, bilaterally, symmetrically; in a localization consistent with the intermediate reticular zone of the bulbopontine area (Table II). The clusters are projected onto the specific template performed for this study from the 61 averaged subjects with normal MRI. (c) Maximum of correlation between gray matter loss and ODI (same as b), projected onto the brainstem template from Diedrichsen [2006].
Figure 3
Figure 3
Correlations between gray matter decrease and SRBDs using ODI criteria. An inverse correlation between gray matter volume and oxyhemoglobin desaturation index (ODI) is present in the brainstem with an extension to the cerebellum. Results are displayed with a P < 0.05 threshold, corrected for multiple comparisons, at the cluster level. Results are presented in neurological convention (i.e., left side of the brain is on the left side of the figure). (a) Projections map (SPM2) showing the correlation between brainstem and SRBDs. No correlation can be seen outside the brainstem and cerebellum. (b) Maximum of correlation between gray matter loss and AHI. Note that the cluster is extended in the upper medulla/inferior pontine region, close to the ventricular surface, bilaterally, almost symmetrically; in a localization consistent with the intermediate reticular zone of the bulbopontine area (see stereotaxic coordinates (MNI) in Table II). The clusters are projected onto the specific template performed for this study from the 61 averaged subjects with normal MRI.

References

    1. Abramov AY,Scorziello A,Duchen MR ( 2007): Three distinct mechanisms generate oxygen free radicals in neurons and contribute to cell death during anoxia and reoxygenation. J Neurosci 27: 1129–1138.
    1. American Academy of Sleep Medicine Task Force ( 1999): Sleep‐related breathing disorders in adults: Recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 22: 667–689.
    1. Baldwin CM,Kapur VK,Holberg CJ,Rosen C,Nieto FJ ( 2004): Associations between gender and measures of daytime somnolence in the Sleep Heart Health Study. Sleep 27: 305–311.
    1. Barthelemy JC,Pichot V,Dauphinot V,Celle S,Laurent B,Garcin A,Maudoux D,Kerleroux J,Lacour JR,Kossovsky M,Gaspoz JM, Roche F ( 2007): Autonomic nervous system activity and decline as prognostic indicators of cardiovascular and cerebrovascular events: The ‘PROOF’ study. Study design and population sample. Associations with sleep‐related breathing disorders: The ‘SYNAPSE’ study. Neuroepidemiology 29: 18–28.
    1. Bartlett DJ,Rae C,Thompson CH,Byth K,Joffe DA,Enright T,Grunstein RR ( 2004): Hippocampal area metabolites relate to severity and cognitive function in obstructive sleep apnea. Sleep Med 5: 593–596.
    1. Beebe DW,Gozal D ( 2002): Obstructive sleep apnea and the prefrontal cortex: Towards a comprehensive model linking nocturnal upper airway obstruction to daytime cognitive and behavioral deficits. J Sleep Res 11: 1–16.
    1. Benarroch EE ( 2007): Brainstem respiratory control: Substrates of respiratory failure of multiple system atrophy. Mov Disord 22: 155–161.
    1. Diedrichsen J ( 2006): A spatially unbiased atlas template of the human cerebellum. Neuroimage 33: 127–138.
    1. Good CD,Johnsrude IS,Ashburner J,Henson RN,Friston KJ,Frackowiak RS ( 2001): A voxel‐based morphometric study of ageing in 465 normal adult human brains. Neuroimage 14(1 Part 1): 21–36.
    1. Johns MW ( 1991): A new method for measuring daytime sleepiness: The Epworth sleepiness scale. Sleep 14: 540–545.
    1. Kono M,Tatsumi K,Saibara T,Nakamura A,Tanabe N,Takiguchi Y,Kuriyama T ( 2007): Obstructive sleep apnea syndrome is associated with some components of metabolic syndrome. Chest 131: 1387–1392.
    1. Launois SH,Pepin JL,Levy P ( 2007): Sleep apnea in the elderly: A specific entity? Sleep Med Rev 11: 87–97.
    1. Leech RW,Alvord EC Jr ( 1977): Anoxic‐ischemic encephalopathy in the human neonatal period. The significance of brain stem involvement. Arch Neurol 34: 109–113.
    1. Lemaitre H,Crivello F,Grassiot B,Alperovitch A,Tzourio C,Mazoyer B ( 2005): Age‐ and sex‐related effects on the neuroanatomy of healthy elderly. Neuroimage 26: 900–911.
    1. Lindenberg R ( 1963): Patterns of CNS vulnerability in acute hypoxaemia, including anesthetic accidents. Selective vulnerability of the brain in hypoxaemia 184–209.
    1. Macey PM,Henderson LA,Macey KE,Alger JR,Frysinger RC,Woo MA,Harper RK,Yan‐Go FL,Harper RM ( 2002): Brain morphology associated with obstructive sleep apnea. Am J Respir Crit Care Med 166: 1382–1387.
    1. Morrell MJ,McRobbie DW,Quest RA,Cummin AR,Ghiassi R,Corfield DR ( 2003): Changes in brain morphology associated with obstructive sleep apnea. Sleep Med 4: 451–454.
    1. Munoz R,Duran‐Cantolla J,Martinez‐Vila E,Gallego J,Rubio R,Aizpuru F,De La Torre G ( 2006): Severe sleep apnea and risk of ischemic stroke in the elderly. Stroke 37: 2317–2321.
    1. Naegele B,Launois SH,Mazza S,Feuerstein C,Pepin JL,Levy P ( 2006): Which memory processes are affected in patients with obstructive sleep apnea? An evaluation of 3 types of memory. Sleep 29: 533–544.
    1. O'Donoghue FJ,Briellmann RS,Rochford PD,Abbott DF,Pell GS,Chan CH,Tarquinio N,Jackson GD,Pierce RJ ( 2005): Cerebral structural changes in severe obstructive sleep apnea. Am J Respir Crit Care Med 171: 1185–1190.
    1. Oeverland B,Skatvedt O,Kvaerner KJ,Akre H ( 2002): Pulseoximetry: Sufficient to diagnose severe sleep apnea. Sleep Med 3: 133–138.
    1. Parenti A,Macchi V,Snenghi R,Porzionato A,Scaravilli T,Ferrara SD,De Caro R ( 2005): Selective stroke of the solitary tract nuclei in two cases of central sleep apnoea. Clin Neuropathol 24: 239–246.
    1. Parish JM,Somers VK ( 2004): Obstructive sleep apnea and cardiovascular disease. Mayo Clin Proc 79: 1036–1046.
    1. Pavlova MK,Duffy JF,Shea SA ( 2008): Polysomnographic respiratory abnormalities in asymptomatic individuals. Sleep 31: 241–248.
    1. Smith RP,Argod J,Pepin JL,Levy PA ( 1999): Pulse transit time: An appraisal of potential clinical applications. Thorax 54: 452–457.
    1. Wolkove N,Elkholy O,Baltzan M,Palayew M ( 2007): Sleep and aging, Part 1: Sleep disorders commonly found in older people. CMAJ 176: 1299–1304.
    1. Young T,Palta M,Dempsey J,Skatrud J,Weber S,Badr S ( 1993): The occurrence of sleep‐disordered breathing among middle‐aged adults. N Engl J Med 328: 1230–1235.
    1. Young T,Peppard PE,Gottlieb DJ ( 2002): Epidemiology of obstructive sleep apnea: A population health perspective. Am J Respir Crit Care Med 165: 1217–1239.

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