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Journal of Clinical and Experimental Neuropsychology Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/ncen19
Obstructive Sleep Apnea Syndrome: Pathogenesis of Neuropsychological Deficits Marc-André Bédard b
a b
, Jacques Montplaisir
a c
,
b
François Richer , Isabelle Rouleau & Jacques Malo a
a
Hôpital du Sacré-Coeur and Université de Montréal ,
b
Hôpital Notre-Dame and Université du Québec à Montréal , c
Centre d'étude du sommeil , Hôpital du Sacré-Coeur , 5400, Quest, Boul Gouin, Montréal (Québec), Canada , H4J 1C5 Published online: 04 Jan 2008.
To cite this article: Marc-André Bédard , Jacques Montplaisir , François Richer , Isabelle Rouleau & Jacques Malo (1991) Obstructive Sleep Apnea Syndrome: Pathogenesis of Neuropsychological Deficits, Journal of Clinical and Experimental Neuropsychology, 13:6, 950-964, DOI: 10.1080/01688639108405110 To link to this article: http://dx.doi.org/10.1080/01688639108405110
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content.
Downloaded by [McGill University Library] at 12:44 15 December 2014
This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sublicensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Journal of Clinical and Experimental Neuropsrchology 1991, Vol. 13, NO. 6, pp. 950-964
0168-8634#1/1306-0950$3.00 Q Swets & Bitlinger
Obstructive Sleep Apnea Syndrome: Pathogenesis of Neuropsychological Deficits*
Downloaded by [McGill University Library] at 12:44 15 December 2014
Marc-Andre Bedard’p *, Jacques Montplaisir’, Fransois Richer2, Isabelle Rouleau*, and Jacques Malo’ ‘Hapita1 du Sacre-Coeur and UniversitC de Montreal 2HBpital Notre-Dame and Universite du Quebec A Montreal
ABSTRACT Neuropsychological deficits have been documented in patients with obstructive sleep apnea syndrome (OSAS). Both nocturnal hypoxemia and impairment of daytime vigilance have been suggested as the pathogenesis of these deficits, yet it remains difficult to find good correlations between cognitive deficits and either of these physiological parameters. In the present study, 10 normal controls were compared to 10 moderately and 10 severely apneic patients, all recorded in a sleep laboratory for two consecutive nights, with a vigilance and neuropsychological assessment made during the intervening day. Relative to the controls, moderate and severe OSAS showed differencesin many cognitive functions, although the severely affected showed the greater differences. Moreover, severe apneics were also worse than moderate apneics on tests that were found to be normal in the latter group. This suggests a discontinuity in the appearance of neuropsychological deficits as OSAS progresses. Further analyses revealed that reductions in general intellectual measures, as well as in executive and psychomotor tasks were all attributable to the severity of hypoxemia, while other attention and memory deficits were related to vigilance impairment. Therefore,both vigilance impairment and nocturnal hypoxemia may differentially contribute to the cognitive dysfunctions found in OSAS.
* We thank Dr Tort Nielsen who kindly revised the manuscript and Dr Diane Boivin who conducted the medical examinations. We are also grateful to Dr Dominique Lorrain for her assistance with statistical analyses. This work was supported by the “Fonds de la Recherche en Sante du Quebec” and the Medical Research Council of Canada. Address for correspondence and reprint requests to: Jacques Montplaisir, MD. Ph.D., Centre d’etude du sommeil, Hapital du Sacr&Coeur, 5400, Ouest, Boul Gouin, Montreal (Quebec), Canada, H4J 1C5. Accepted for publication: February 28, 1991.
Downloaded by [McGill University Library] at 12:44 15 December 2014
NEUROPSYCHOLOGICAL DEFICITS IN OSAS
951
Obstructive sleep apnea syndrome (OSAS) is a respiratory impairment characterized by repetitive cessations of breathing during sleep due to the obstruction of upper airways. The pathophysiology of OSAS involves both anatomical factors, such as upper airway narrowing, and functional factors, such as defective activation of upper airway dilatory muscles (Bradley & Phillipson, 1985; Kuna & Remmers, 1985). The prevalence of OSAS has been estimated at between 1% and 10% of the general population (Lavie, 1983; Peter et al., 1985), but this proportion increases with age, averaging 30% after the age of 65 (Shepard, 1988). To make the diagnosis of OSAS, the number of apneas per hour of sleep (apnea index) should exceed five (Association of Sleep Disorders Centers, 1979), but this is a minimum criterion because in several patients the apnea index may be greater than 50. Clinical features of OSAS include snoring, sleep disruption, nocturnal hypoxemia and, i n severe cases, cardiovascular complications which may lead to sudden death during sleep (Guillemineault, 1989). More often, however, apneic patients complain of vigilance impairment that may extend from the simple inability to perform everyday tasks to a real daytime sleepiness. Moreover, impairment of cognitive functions have also been documented in OSAS, principally in the areas of memory, attention, and visuo-constructive abilities (Findley et al., 1986; Greenberg, Watson, & Deptula, 1987; Kischinovsky, Jennum, Mortenssen, & Wildschiodtz, 1987; Norman, Bonnie & Cohn, 1986; Sloan, Craft, & Walsh, 1989; Watson, Greenberg, & Deptula, 1985). Currently, opinions are divided concerning the pathogenesis of the cognitive impairments in OSAS. Some authors (Nichols, Kapen, & Greiffenstein, 1988) believe that these intellectual deteriorations have an unspecific pathogenesis usually related to other uncontrolled neuromedical factors, and that without these factors, cognitive functions of apneic patients would not be more affected than other populations of hypersomniacs (Aguirre, Broughton, & Stuss, 1985; 0110 et al., 1987; Rogers & Rosenberg, 1990). On the other hand, others assume that in OSAS, low performances on neuropsychological tests should correlate with nocturnal blood oxygen saturation (SaO,), since in chronic obstructive pulmonary disease (COPD), another population of hypoxemic patients, such linear relationships have been found with daytime blood gas [Fix, Golden, Daughton, Kass, & Bell, 1982; Grant, Heaton, McSweeny, Adams, & Timms, 1982; Grant et al., 1987; Prigatano, Parson, Wright, Levin, & Hawryluk, 1983). In a population of heavy snorers (Berry, Webb, Block, Bauer, & Switzer, 1986), results have shown a negative correlation between the number of SaO, drops of at least 4 % from the baseline, and scores on general intellectual (IQ) or memory (MQ) scales. Unfortunately, neither sleep, nor vigilance variables, nor different levels of SaO, were reported in this study. It is thus difficult to conclude that the measures of cognitive performance are related to nocturnal hypoxemia and not to sleep disruption or to the drowsy state that is also often associated with severe snoring. This latter question was also investigated in arecent study (Telakivi et al., 1988) which revealed cognitive functioning to be more closely related to daytime alertness than to SaO, values in a population of habitual severe snorers.
Downloaded by [McGill University Library] at 12:44 15 December 2014
952
MARC-ANDe BEDARD ET AL.
In a population of OSAS, Greenberg et al., (1987) found that sleep apnea patients performed significantly worse than other hypersomniacs on 7 of 14 psychometric tests and on a rating of global neuropsychological impairment. These authors concluded that nocturnal hypoxemia had an important role in the pathogenesis of the cognitive deficits found in OSAS, although they did not find the expected correlation between the psychometric tests and the respiratory measures. The authors consider that such correlations in OSAS are the exeption rather than the rule because: (1) the variability in the severity of apneas from night to night in mildly affected patients reduced the predictability of daytime symptoms; and (2) a ceiling effect in the measurement of nocturnal hypoxemia in severely apneic patients weakened also the power of correlational tests. These methodological problems could be corrected with a non-correlational approach comparing cognitive functioning in subpopulations of OSAS selected for various degrees of hypoxemia severity. Such comparisons were conducted by Findley et al. (1986), who found more severe cognitive dysfunctions in patients with hypoxemia than in patients without hypoxemia. However, in this study the hypoxemic group had oxygen desaturation even during the day and also had hypercapnia, probably related to restrictive or obstructive pulmonary diseases. Therefore, although significant correlations were found between cognitive deficits and hypoxemia levels both during sleep and during the day, the specific contribution of sleep apneas to the cognitive dysfunction could not be determined. Sloan et al., (1989) obtained quite different results, since their comparisons of hypoxemic and non-hypoxemic OSAS patients controlled for daytime blood gas, did not show any difference on tests of memory and IQ scales. These authors conclude that cognitive deficts in OSAS are primarily attributable to the impaired vigilance, even though they provided no direct evidence of such a relationship. In summary, although several observations indicate that both vigilance impairment and sleep respiratory impairment may contribute to neuropsychological deficits in OSAS, the specific contribution of each factor is still unknown. Preliminary results obtained in our laboratory (Bkdard, Montplaisir, Rouleau, & Malo, 1989) suggested that both factors contribute and may in fact produce different cognitive deficits. So the first aim of the present study was to assess this question of the respective contributions of nocturnal hypoxemia and vigilance impairment on the cognitive deficits of OSAS. Moreover, the lack of correlation between measures of a given deficit and either of the progressive pathogenic factors may be caused by a discontinuity in the appearance of the deficits with the evolution of the syndrome. Therefore, the second aim of the study was to demonstrate such a discontinuity of the deficits. We propose that for some functions, impairment will be evident at an early stage and will increase with the severity of the syndrome, while for other functions, deficits will not be present before a critical level of severity.
NEUROPSYCHOLOGICAL DEFICITS IN OSAS
953
METHODS
Downloaded by [McGill University Library] at 12:44 15 December 2014
Subjects Thirty French-Canadian subjects, aged 35 to 65 years, participated in the study. This sample included 10 normal controls, 10 moderately apneic patients and 10 severely apneic patients, matched for age, sex and daytime blood gas levels. Normal subjects were chosen from the general population and were paid for their participation. Apneic patients were males consulting for daytime sleepiness at our Sleep Disorders Center. Criteria for inclusion in the severe OSAS group were a sleep apnea index exceeding 30 and a percentage of total sleep time with SaO, under 80% (% sleep Sa0,
Journal of Clinical and Experimental Neuropsychology Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/ncen19
Obstructive Sleep Apnea Syndrome: Pathogenesis of Neuropsychological Deficits Marc-André Bédard b
a b
, Jacques Montplaisir
a c
,
b
François Richer , Isabelle Rouleau & Jacques Malo a
a
Hôpital du Sacré-Coeur and Université de Montréal ,
b
Hôpital Notre-Dame and Université du Québec à Montréal , c
Centre d'étude du sommeil , Hôpital du Sacré-Coeur , 5400, Quest, Boul Gouin, Montréal (Québec), Canada , H4J 1C5 Published online: 04 Jan 2008.
To cite this article: Marc-André Bédard , Jacques Montplaisir , François Richer , Isabelle Rouleau & Jacques Malo (1991) Obstructive Sleep Apnea Syndrome: Pathogenesis of Neuropsychological Deficits, Journal of Clinical and Experimental Neuropsychology, 13:6, 950-964, DOI: 10.1080/01688639108405110 To link to this article: http://dx.doi.org/10.1080/01688639108405110
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content.
Downloaded by [McGill University Library] at 12:44 15 December 2014
This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sublicensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Journal of Clinical and Experimental Neuropsrchology 1991, Vol. 13, NO. 6, pp. 950-964
0168-8634#1/1306-0950$3.00 Q Swets & Bitlinger
Obstructive Sleep Apnea Syndrome: Pathogenesis of Neuropsychological Deficits*
Downloaded by [McGill University Library] at 12:44 15 December 2014
Marc-Andre Bedard’p *, Jacques Montplaisir’, Fransois Richer2, Isabelle Rouleau*, and Jacques Malo’ ‘Hapita1 du Sacre-Coeur and UniversitC de Montreal 2HBpital Notre-Dame and Universite du Quebec A Montreal
ABSTRACT Neuropsychological deficits have been documented in patients with obstructive sleep apnea syndrome (OSAS). Both nocturnal hypoxemia and impairment of daytime vigilance have been suggested as the pathogenesis of these deficits, yet it remains difficult to find good correlations between cognitive deficits and either of these physiological parameters. In the present study, 10 normal controls were compared to 10 moderately and 10 severely apneic patients, all recorded in a sleep laboratory for two consecutive nights, with a vigilance and neuropsychological assessment made during the intervening day. Relative to the controls, moderate and severe OSAS showed differencesin many cognitive functions, although the severely affected showed the greater differences. Moreover, severe apneics were also worse than moderate apneics on tests that were found to be normal in the latter group. This suggests a discontinuity in the appearance of neuropsychological deficits as OSAS progresses. Further analyses revealed that reductions in general intellectual measures, as well as in executive and psychomotor tasks were all attributable to the severity of hypoxemia, while other attention and memory deficits were related to vigilance impairment. Therefore,both vigilance impairment and nocturnal hypoxemia may differentially contribute to the cognitive dysfunctions found in OSAS.
* We thank Dr Tort Nielsen who kindly revised the manuscript and Dr Diane Boivin who conducted the medical examinations. We are also grateful to Dr Dominique Lorrain for her assistance with statistical analyses. This work was supported by the “Fonds de la Recherche en Sante du Quebec” and the Medical Research Council of Canada. Address for correspondence and reprint requests to: Jacques Montplaisir, MD. Ph.D., Centre d’etude du sommeil, Hapital du Sacr&Coeur, 5400, Ouest, Boul Gouin, Montreal (Quebec), Canada, H4J 1C5. Accepted for publication: February 28, 1991.
Downloaded by [McGill University Library] at 12:44 15 December 2014
NEUROPSYCHOLOGICAL DEFICITS IN OSAS
951
Obstructive sleep apnea syndrome (OSAS) is a respiratory impairment characterized by repetitive cessations of breathing during sleep due to the obstruction of upper airways. The pathophysiology of OSAS involves both anatomical factors, such as upper airway narrowing, and functional factors, such as defective activation of upper airway dilatory muscles (Bradley & Phillipson, 1985; Kuna & Remmers, 1985). The prevalence of OSAS has been estimated at between 1% and 10% of the general population (Lavie, 1983; Peter et al., 1985), but this proportion increases with age, averaging 30% after the age of 65 (Shepard, 1988). To make the diagnosis of OSAS, the number of apneas per hour of sleep (apnea index) should exceed five (Association of Sleep Disorders Centers, 1979), but this is a minimum criterion because in several patients the apnea index may be greater than 50. Clinical features of OSAS include snoring, sleep disruption, nocturnal hypoxemia and, i n severe cases, cardiovascular complications which may lead to sudden death during sleep (Guillemineault, 1989). More often, however, apneic patients complain of vigilance impairment that may extend from the simple inability to perform everyday tasks to a real daytime sleepiness. Moreover, impairment of cognitive functions have also been documented in OSAS, principally in the areas of memory, attention, and visuo-constructive abilities (Findley et al., 1986; Greenberg, Watson, & Deptula, 1987; Kischinovsky, Jennum, Mortenssen, & Wildschiodtz, 1987; Norman, Bonnie & Cohn, 1986; Sloan, Craft, & Walsh, 1989; Watson, Greenberg, & Deptula, 1985). Currently, opinions are divided concerning the pathogenesis of the cognitive impairments in OSAS. Some authors (Nichols, Kapen, & Greiffenstein, 1988) believe that these intellectual deteriorations have an unspecific pathogenesis usually related to other uncontrolled neuromedical factors, and that without these factors, cognitive functions of apneic patients would not be more affected than other populations of hypersomniacs (Aguirre, Broughton, & Stuss, 1985; 0110 et al., 1987; Rogers & Rosenberg, 1990). On the other hand, others assume that in OSAS, low performances on neuropsychological tests should correlate with nocturnal blood oxygen saturation (SaO,), since in chronic obstructive pulmonary disease (COPD), another population of hypoxemic patients, such linear relationships have been found with daytime blood gas [Fix, Golden, Daughton, Kass, & Bell, 1982; Grant, Heaton, McSweeny, Adams, & Timms, 1982; Grant et al., 1987; Prigatano, Parson, Wright, Levin, & Hawryluk, 1983). In a population of heavy snorers (Berry, Webb, Block, Bauer, & Switzer, 1986), results have shown a negative correlation between the number of SaO, drops of at least 4 % from the baseline, and scores on general intellectual (IQ) or memory (MQ) scales. Unfortunately, neither sleep, nor vigilance variables, nor different levels of SaO, were reported in this study. It is thus difficult to conclude that the measures of cognitive performance are related to nocturnal hypoxemia and not to sleep disruption or to the drowsy state that is also often associated with severe snoring. This latter question was also investigated in arecent study (Telakivi et al., 1988) which revealed cognitive functioning to be more closely related to daytime alertness than to SaO, values in a population of habitual severe snorers.
Downloaded by [McGill University Library] at 12:44 15 December 2014
952
MARC-ANDe BEDARD ET AL.
In a population of OSAS, Greenberg et al., (1987) found that sleep apnea patients performed significantly worse than other hypersomniacs on 7 of 14 psychometric tests and on a rating of global neuropsychological impairment. These authors concluded that nocturnal hypoxemia had an important role in the pathogenesis of the cognitive deficits found in OSAS, although they did not find the expected correlation between the psychometric tests and the respiratory measures. The authors consider that such correlations in OSAS are the exeption rather than the rule because: (1) the variability in the severity of apneas from night to night in mildly affected patients reduced the predictability of daytime symptoms; and (2) a ceiling effect in the measurement of nocturnal hypoxemia in severely apneic patients weakened also the power of correlational tests. These methodological problems could be corrected with a non-correlational approach comparing cognitive functioning in subpopulations of OSAS selected for various degrees of hypoxemia severity. Such comparisons were conducted by Findley et al. (1986), who found more severe cognitive dysfunctions in patients with hypoxemia than in patients without hypoxemia. However, in this study the hypoxemic group had oxygen desaturation even during the day and also had hypercapnia, probably related to restrictive or obstructive pulmonary diseases. Therefore, although significant correlations were found between cognitive deficits and hypoxemia levels both during sleep and during the day, the specific contribution of sleep apneas to the cognitive dysfunction could not be determined. Sloan et al., (1989) obtained quite different results, since their comparisons of hypoxemic and non-hypoxemic OSAS patients controlled for daytime blood gas, did not show any difference on tests of memory and IQ scales. These authors conclude that cognitive deficts in OSAS are primarily attributable to the impaired vigilance, even though they provided no direct evidence of such a relationship. In summary, although several observations indicate that both vigilance impairment and sleep respiratory impairment may contribute to neuropsychological deficits in OSAS, the specific contribution of each factor is still unknown. Preliminary results obtained in our laboratory (Bkdard, Montplaisir, Rouleau, & Malo, 1989) suggested that both factors contribute and may in fact produce different cognitive deficits. So the first aim of the present study was to assess this question of the respective contributions of nocturnal hypoxemia and vigilance impairment on the cognitive deficits of OSAS. Moreover, the lack of correlation between measures of a given deficit and either of the progressive pathogenic factors may be caused by a discontinuity in the appearance of the deficits with the evolution of the syndrome. Therefore, the second aim of the study was to demonstrate such a discontinuity of the deficits. We propose that for some functions, impairment will be evident at an early stage and will increase with the severity of the syndrome, while for other functions, deficits will not be present before a critical level of severity.
NEUROPSYCHOLOGICAL DEFICITS IN OSAS
953
METHODS
Downloaded by [McGill University Library] at 12:44 15 December 2014
Subjects Thirty French-Canadian subjects, aged 35 to 65 years, participated in the study. This sample included 10 normal controls, 10 moderately apneic patients and 10 severely apneic patients, matched for age, sex and daytime blood gas levels. Normal subjects were chosen from the general population and were paid for their participation. Apneic patients were males consulting for daytime sleepiness at our Sleep Disorders Center. Criteria for inclusion in the severe OSAS group were a sleep apnea index exceeding 30 and a percentage of total sleep time with SaO, under 80% (% sleep Sa0,
