The Effects of Sleep-Related Breathing Disorders on Waking Performance

Chapter 9
The Effects of Sleep-Related Breathing
Disorders on Waking Performance
A. Büttner(-Teleaga)1,2
1Woosuk University, Samnye-up, Wanju-gun, Jeonbuk-do,
2University of Witten-Herdecke, Witten,
1South Korea
2Germany

Sleep Disorders

Edited by Chris Idzikowski, ISBN 978-953-51-0293-9, 202 pages, Publisher: InTech, Chapters published March 14, 2012 under CC BY 3.0 license
DOI: 10.5772/1500
Edited Volume

1. Introduction
Sleep is a necessary and reversible behavioural state of perception, cognition, psyche and
physical conditions. Abnormal sleep behaviours may include e.g. difficulties in falling
asleep, breathing difficulties such as different kinds of apneas, sleep paralysis, hypnagogic
hallucinations, sleep onset-REM, leg movements, sleepwalking, sleep talking, tooth grinding
and other physical activities. These anomalies involving sleep processes also include sleep
itself, dream imagery or muscle weakness.
Within sleep there are two separate states, non-rapid eye movement (NREM) and rapid eyes
movement (REM). REM sleep is defined by EEG activation, muscle atony, and episodic
bursts of rapid eye movement. NREM (non-REM) sleep is subdivided into four stages
(stages 1, 2, 3 and 4 – Rechtschaffen & Kales) or three stages (N1, N2 and N3 – AASM),
which are defined by the electroencephalogram (EEG). The NREM stages are parallel to the
depth of sleep continuum (lowest in stage 1 and highest in stage 4 sleep).
NREM sleep and REM sleep continue to alternate through the night in cyclically. REM sleep
episodes become longer across the night, stages 3 and 4 become shorter across the night.
Sleep disorders have an impact on the structure and distribution of sleep. A distinction is
important in diagnosis and in the choice of treatments. There are three very important sleep
disorders: Insomnia, Narcolepsy and Sleep Apnea Syndrome.
Altogether, in Western Europe already suffer more than 10 % of the population from Sleep-
Awake-Disturbances which has to be treated urgently; 800,000 from Sleep Apnea Syndromes
and 25,000 from Narcolepsy (PETER et al. 1995).
1. Insomnia is a sleeplessness and includes a decreased total sleep time, a poor sleep
efficiency too little and a poor sleep quality caused by one or more of the following:
trouble falling asleep (delayed sleep latency), waking up a lot during the night with
trouble returning to sleep, waking up too early in the morning, and/or having unrefreshing
sleep/not feeling well rested (even after sleeping 7 to 8 hours at night).
Under this criterion the frequency is in the western industrial countries between 20-30
% in which about 10-15 % suffer under a very severe illness and 40 % of all depressions
may be preceded by insomnia first.
2. Narcolepsy is a genetic disorder and characterized by sleep onset REM sleep,
hypnagogic hallucinations, sleep paralysis, cataplexy and excessive daytime sleepiness.
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The exact prevalence of the general population is unknown. Great differences exist in its
appearance frequency. So the frequency of Japan is 0.16 % and of Israel 0.0002 %.
Central Europe (0.006 %) and the USA (0.06-0.1 %) are located in the middle.
3. Sleep Apnea Syndromes (SAS) are common disorders, which are characterized by
repeated oropharyngeal occlusions occurring during the sleep time (sleep-related
breathing problems, intermittent hypoxemia) and may be associated with suppression
of SWS sleep (disrupted and fragmentized sleep architecture). Due to intermittent
hypoxemia and disrupted sleep architecture, SAS leads to impaired daytime
functioning in various (neuro)psychological and affective domains and has been
associated with increased morbidity and mortality, principally from adipositas,
cardiovascular and neurological diseases.
The prevalence of moderate SAS (AHI >15/h) is 9% in male and 4% in female,
respectively. 25-30 % Sleep Apnea Syndromes were described at patients with
hypertension and 35-45 % with patients with on the left heart-failure. The SAS
frequency increases with an advancing age and reaches their peak at the age from 50 to
70 years. 80% of the patients suffer under excessive daytime sleepiness and a reduced
sustained attention. Resulting from this it comes to performance losses both
professional and in the ability to drive motor vehicles.
Fragmentation of sleep and increased frequency of arousals occur in association with this three
disorders and a number of other sleep disorders as well as with medical disorders involving
physical pain or discomfort.
In this chapter, the author will describe neuropsychological dysfunctions/courses and
neuropsychiatric syndromes due sleep disorders which were characterized by
1. excessive daytime sleepiness
2. attention deficit,
3. memory dysfunction,
4. executive dysfunction,
5. driving difficulties,
6. motivation and emotional deficits,
7. psychiatric consequences (e.g. depression, anxiety) and
8. lack of ability to recognize the effects of behaviour.
There are wide varieties of difficulties in assessment, treatment and rehabilitation for cognitive
impairment, psychiatric disorders and behavioural disability after sleep disorders.
In our studies we used neuropsychological and neuropsychiatric methods in different patient
groups in a sleep laboratory. Over the past five years we have been testing and treating more
than 2000 patients with different sleep disorders and more than 5000 neurological patients.
During admission to the clinic, all patients were selected according to their clinical diagnosis
(ICD-10) and were examined neurologically, (neuro)psychologically, psychiatrically and
medically. The test persons must not suffer from any severe psychiatric disorders. The study
was carried out involving randomly selected patients with sleep disorders.
2. Excessive daytime sleepiness in patients with Sleep Apnea Syndrome
2.1 State of research
2.1.1 Sleep Apnea Syndromes and neuropsychological disorders
In addition to nocturnal Sleep Apnea Syndrome symptoms there are a lot of daytime
symptoms. It is assumed that the reduced sleep quality, arising out of deep sleep or REMwww.
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suppression, resulting in increased nocturnal arousal responses, or constantly occurring
waking or a reduced relaxation function (Weeß et al. 1998a/b) and cognitive damage caused
by intermittent hypoxia (Montplaisir et al. 1992). As the main symptom is excessive daytime
sleepiness (EDS) is considered.
It is also assumed that the OSAS accompanying Insomnia and sleepiness influence cognitive
functions (Jennum et al. 1993). As reported by Schwarzenberger et al. (1987) that patients
with EDS have complaints and problems in situations of physical rest and during prolonged
monotonous concentration tasks. A study by Kales (1985) showed that 76% of OSAS patients
have cognitive deficits in the areas of thinking, learning ability, memory, communication
and the ability to learn new information. Naëgelé et al. (1995) were able to establish in Sleep
Apnea Syndrome patients that they were reduced at executive functions when these tasks
involve the acquisition of information to memory processing. Another study by Cassel et al.
(1995) showed that Sleep Apnea Syndrome patients have a reduced non-verbal performance
and processing speed. Regarding the central nervous system activation (alertness), selective
attention and sustained attention in Sleep Apnea Syndrome patients Kotterba et al. (1998)
found, that they were impaired, and that they have a reduced vigilance (Barbè et al. 1998).
The cause of cognitive and neuropsychological deficits in the EDS itself, the sleep
fragmentation and arousals and nocturnal hypoxemia are discussed (Findley et al. 1986,
Greenberg et al. 1987, Guilleminault et al. 1988, Colt et al, 1991, Bédard et al. 1991, Roehrs et
al. 1995).
2.1.2 Causes of neuropsychological deficits (Büttner 2001, 2009)
Two concepts play a central role, first, the hypoxia and the other the disturbed sleep
architecture in the causes of the neuropsychological and/or cognitive deficits in Sleep
Apnea Syndrome patients.
Both factors appear usually occur together, so that it is hardly possible to separate the two.
Several studies confirm the link between nocturnal oxygen desaturation and
neuropsychological deficits. Greenberg et al. (1987) showed, for example, that the nocturnal
hypoxia is the cause of the neuropsychological deficits and daytime sleepiness. In another
study conducted by Findley et al. (1986) showed that there is a correlation between hypoxia
during sleep and wakefulness with the degree of cognitive impairment, but not between
sleep fragmentation and the cognitive functions. In a study of Kotterba et al. (1998), various
neuropsychological parameters correlate with the degree of hypoxia, but not with the
arousal index and AHI. Montplaisir et al. (1992) describe the nocturnal hypoxia as the best
predictor for both daytime alertness as well as daytime sleepiness.
For other investigators, the cause of the neuropsychological deficits such as those of daytime
sleepiness exist in the disruption of sleep patterns or sleep fragmentation, accompanied by a
reduction in the proportion of REM and slow wave sleep. According to Bonnet et al. (1985)
healthy persons’ sleep fragmentation leads to neuropsychological impairment. Other
researchers such as Telakivi et al. (1988) and Guilleminault et al. (1988) find that sleep
fragmentation has an important impact on neuropsychological deficits. This allowed
Guilleminault et al. (1988) to conclude in a study that the sleep fragmentation would be the
best predictor of the occurrence of daytime fatigue is, and that there is no relationship
between daytime sleepiness and respiratory parameters such as RDI or oxygen
desaturations. This could confirm also by Colt et al. (1991) in a study. Nocturnal hypoxias
were induced during a night under nCPAP therapy and, no effect on daytime sleepiness
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could be found. So it was adopted by this study that the day’s fatigue does not caused by a
decrease of intermittent nocturnal oxygen saturation, but rather by the sleep fragmentation.
Bédard et al. (1991) suggested it was an interaction of both factors; both sleep fragmentation
and nocturnal hypoxia were of great importance in the emergence of decreased vigilance or
neuropsychological deficits, with the hypoxia seemingly playing a larger role in severe
cases. In addition, the daytime sleepiness itself is responsible for the cognitive deficits (Roehrs
et al. 1995).
Other assumptions are that neither the disturbed sleep architecture nor nocturnal hypoxias
play a role for the neuropsychological deficits in OSAS. Thus Ingram et al. (1994) showed
that there are no differences in vigilance between OSAS patients and normal subjects. The
reduction of vigilance could be determined by age. Research of Kotterba et al. (1998) and
Büttner et al. (2004b) were able to contradict these suggestions, as they found differences of
vigilance between OSAS patients and healthy individuals, but no age differences. Severity of
OSAS, as measured by the AHI or RDI, or nCPAP compliance may also play a role (Cassel et
al. 1989, Engleman et al. 1993, John (et al.) 1991, 1992, 1993).
2.1.3 Daytime sleepiness, fall asleep and driving performance (Büttner 2001, 2009)
The ability to drive safely and without accident needs sustained attention and alertness
(Guilleminault et al. 1978, Bradley et al. 1985, Podszus et al. 1986, Findley et al. 1988a/b,
1989b, 1990, 1991, 1995, He et al. 1988, Mitler et al. 1988, Lamphere et al. 1989, Roehrs et al.
1989, Bédard et al. 1991, Cassel et al. 1991a/b, 1993, 1996, Kribbs et al. 1993a/b, ATS 1994,
Martin et al. 1996, Gerdesmeyer et al. 1997, Krieger et al. 1997, Randerath et al. 1997, 1998,
Weeß 1997, Weeß et al. 1998a/b).
Increased daytime sleepiness is one of the most common causes of road accidents. Driver
fatigue is the cause in up to 25% of highway accidents (Langlois et al. 1985, Pack et al. 1994,
Horne et al. 1995). A study of 67 671 non-alcohol-related car accidents in France in the years
1994-1998 showed that the risk of accidents involving fatalities or serious injuries in fatiguerelated
accidents is increased as compared to non-fatigue-related accidents significantly
(Philip 2000). An analysis of fatal accidents on highways in Bavaria in 1991 showed that 49
of 204 accidents (24%) caused by falling asleep at the wheel (Langwieder et al. 1994).
Obstructive Sleep Apnea Syndrome is again one of the most common causes of daytime
sleepiness is increased (American Thoracic Society 1994, McNicholas, 1999).
Reliable data on sleepiness-related causes of accidents due to the German data protection
regulations is not available and caused on it the published data’s are very inconsistent:
According to Seko et al. (1986) 45% of all fatal road accidents were caused by falling asleep at
the wheel or a micro-sleep, but declared by the Federal Statistical Office at Wiesbaden (1988)
only 0.5% of all traffic accidents (Seko et al. 1986, Federal Statistical Office Wiesbaden 1988,
Cassel et al. 1993). A study of Zulley et al. showed that 38% in all traffic accidents on Bavarian
highways were due vigilance reduction and 24% of all serious accidents (Zulley et al. 1995).
The sleep-related vigilance and sustained attention losses were intensified, especially
exacerbated by the effects of biological rhythms (Hildebrandt et al. 1974, Hildebrandt 1976,
Mitler 1991, Cassel et al. 1991c, 1993, Zulley 1995).
As early as 1955 Prokop and Prokop discussed regarding traffic safety and the importance
of fatigue and falling asleep, but without to discuss the sleep-related aspects or causes
(Prokop & Prokop 1955, Cassel et al. 1993). At first in 1978 Guilleminault et al. showed a
possible increased risk for patients with sleep-disordered breathing (Guilleminault et al.
1978, Cassel et al. 1991a/b).
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George et al. (1987) took up this assumption and investigated the accident probability of 27
suspected OSAS patients. In 93% of patients were entered injuries in the accident register of
Motor Vehicle Branch of Manitoba (Canada), but only 54% of the control group participants.
Unfortunately, in seven patients, the polysomnographic confirmation of the diagnosis and
the information on the period of specified accidents are missing (George et al. 1987, Cassel et
al. 1991a/b, Weeß 1997, Weeß et al. 1998 a/b). Findley et al. (1988b) found that 29 OSAS
patients (AHI> 5) a three-fold increased probability of accidents compared to all license
holders of Virginia (USA), and even a seven-fold increased compared to a control group (n =
35). However, Findley et al. didn’t give the information whether the OSAS diagnosis was
already known in the survey (Findley et al. 1988b, Cassel et al. 1991a/b, Weeß 1997, Weeß et
al. 1998 a/b). Later studies and studies by Cassel et al. (1991a/b, 1996), the ATS (1994) and
Krieger et al. (1997) confirmed these findings. Thus, patients with Sleep Apnea Syndrome
seem increasingly to suffer from severe fatigue and falling asleep while driving (see also
George et al. 1987, 1996b, Findley et al. 1988b). With increasing impairment of those affected
persons by the symptoms of Obstructive Sleep Apnea are also accumulated self-inflicted,
sustained attention-related injuries (Cassel et al. 1991a/b, 1996, ATS 1994, Kruger et al. 1997).
According to Young et al. (1997), the relative risk of an accident within five years, causing
increased for men with sleep-related breathing disorders by factor of 3. Several studies show
a minimum of a 2-fold to 3-fold, up to 7-fold increased risk of accidents (George et al. 1987,
1999, Findley et al. 1988, 2000, Horne & Reyner 1995, Wu & Yan-Go 1996, Young et al. 1997,
Barbé et al. 1998, Terán-Santos et al. 1999, Horstmann et al. 2000, LLoberes et al. 2000,
Sharma & Sharma 2008). For example, George et al. (1999) investigated the relationship
between accident rates and the number of traffic offenses in OSAS patients, with the result
that the frequency of accidents and the number of traffic violations during a period of five
years was significantly higher compared to a control group.
A special group in this context represent professional drivers, bus and truck drivers, because
they spend a lot of professional time on the road and also with some larger vehicles usually
dangerous cargo or other people, so that probably occur in an accident caused considerable
damage and injury. These people have to suffer through their work and the associated
lifestyle at increased risk of interference with OSAS. Thus for example truck drivers have a
very irregular sleep-wake rhythm (Stradling 1989, Stoohs et al. 1995). In 1994 Stoohs et al.
researched the influence of sleep-disordered breathing (SDB) and obesity among commercial
drivers of large trucks. Drivers with SDB cause twice as many accidents per 1000 driven miles,
than that without SDB, and obesity, the accident rate still increased. Accidents caused by
overtiredness-related un-roadworthy and related offenses are likely among professional
drivers having accepted a level that is comparable to the drunken crime (Meyer 1990).
The diagnosis of central nervous system stimulation as well as the diagnosis of daytime
sleepiness has therefore central importance in the sleep medical field. Thus, the daytime
sleepiness is on the one hand understood as an important symptom of non-restorative sleep,
but on the other hand can also be closed due to their expression on the severity of this sleep
disorder. Ultimately, their diagnostic evaluation is also an important criterion for therapy
evaluation.
The sleepiness-related medical history or diagnosis is used to assess the clinical and social
impact of daytime sleepiness. In particular, the severity and the social and medical risk will
be assessed. It can also be used as parameters of the differential diagnosis of fatigue. This
anamnesis can be supported by the use of orienting processes or by the method of screening.
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It is used especially in the assessment of type and of frequency about the tendency to fall
asleep, micro-sleep episodes and monotony intolerance at work (especially in monitoring
activities) and to capture the possibility of active participation in road traffic and other social
situations (Walsleben 1992, Weeß 2011).
The Epworth Sleepiness Scale (ESS), the Stanford Sleepiness Scale (SSS), the Multiple Sleep
Latency Test (MSLT) and the Maintenance Wakefulness Test (MWT) are among the methods
that are most widely used for the investigation of daytime sleepiness in sleep disorders. The
ESS reflects the global and subjective severity of daytime sleepiness in eight different
situations and activities of daily living. The SSS is, however, to capture subjective circadian
fluctuations of daytime sleepiness. To objective capture electrophysiological and
standardized tests are often, such as the MSLT and the MWT used to determine the degree
of alertness on the basis of tonic activation.
If, on the basis of questionnaire data and medical history of sleeping on the basis of
suspicion that a pathological daytime sleepiness (Table 1) exists, then objective analysis
methods can be used to measure sleepiness-related functions.
Central nervous system activation
Vigilance
Selected Attention
Divided Attention
Table 1. Sleepiness functions
2.2 Epworth Sleepiness Scale (ESS)
The Epworth Sleepiness Scale (ESS) of Johns (1991) is very often used as a screening method
for detecting the global daytime sleepiness and fall asleep in sleep disorders, especially used
in hypersomnias. It is asked retrospectively, how high is the probability to fall asleep in
eight everyday situations. The scale has a 4-step response format, in which values between 0
and 3 (0 = never to 3 = strongly agree) must be marked and results are added up a total
maximum value of 24.
Following Johns (1991, 1992, Johns & Hocking 1997) a cut-off value ≥ 11 indicates a
pathological daytime sleepiness. Standardization studies for the German-speaking countries
were presented by Büttner et al. (2004c) and Sauter and colleagues (2007). The study found
that 85% of healthy persons achieved a total value < 10, which corresponds to the calculated
cut-off values in other studies (Johns 1991, Johns & Hocking 1997). The test-retest reliability
of the ESS was calculated by Johns (1994) and based on a survey after five months in 87
healthy medical students. It was rtt = .82 (p <.001), even the quality of internal consistency
was confirmed (Cronbach’s alpha = .88 (p <.001).
The ESS has in spite of it being subjective and a global assessment of daytime sleepiness
(Johns 2000) has a very good validity. At a cut-off value > 10 it shows a high sensitivity of
93.5% and – high specificity 98.4%. The ESS is thus a highly reliable and valid procedure.
The short implementation time and simple evaluation makes it very economical and cost
effective. In addition, it can also be used for measuring the effectiveness of nCPAP therapy.
Nevertheless the ESS does not lend itself to capture gradually different levels of sleepiness
(Sangal et al. 1997b) and that four of the eight items have very low selectivity (Rühle et al.
2005).
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2.3 Stanford Sleepiness Scale (SSS)
The Stanford Sleepiness Scale (SSS) of Hoddes et al. (1973) is a scale on which momentary
alertness can be assessed on a grading of 1 to 7 and thus serves to assess the circadian
variations in daytime sleepiness. The scale describes gradual gradations of awareness; it
varies between very alert and drowsy conditions. The alertness descriptions are also
described, each with typical sensations (e.g. some slack, slows, woozy) characterized. Studies
on the sensitivity of the scale showed that ratings in 15-minute intervals represent discrete
changes in the degree of alertness. According to the response ratings point values are
assigned for each time interval, which are then summated.
2.4 Multiple Sleep Latency Test (MSLT)
The Multiple Sleep Latency Test by Carskadon and Dement (1977) recorded the sleep
latency lying down and is recommended for the investigation of daytime sleepiness in
OSAS patients in the ICSD-2. The MSLT is based on the assumption that a strong
physiological sleepiness can reduce the sleep latency (Arand et al. 2005).
For a long time the MSLT has been considered a gold standard for the investigation of
daytime sleepiness (Carskadon et al. 1986). The MSLT (as well as the Maintenance of
Wakefulness Test (MWT)) is often used to determine the alertness with expert’s
investigations, e.g. to assess the driving ability (Poceta et al. 1992). Five times a day
electrophysiological recordings (C3/A2, C4/A1, EOG, EMG) are performed in 2-hour
intervals. The first time of measurement should be from 1.5 to 3 hours after waking. The
patient lies in a darkened room and is asked to fall asleep. During the test procedure, the
patient is monitored with a video recording.
A pathological fall asleep exists, when the medium sleep latency is < 5 minutes (Richardson et
al. 1982). The gray area is between 5-10 minutes and > 10-20 minutes is a normal finding. But
are also divergent standard values of 5-8 minutes; thereby establishing of normal values is
equivalent to a kind of “rule of thumb” (Guilleminault et al. 1994, van den Hoed et al. 1981,
Johns 2000). Although the MSLT perform and should be evaluated strictly according to
objective criteria and standardized, it seems to have low implementation objectivity, because
the results of individual tests vary greatly (Danker-Hopfe et al. 2006). As other reasons for the
inconsistent individual test results Thorpy (1992) describes the different day times and
measuring times and not objectified sleep deprivation and sedative or stimulating effects of
drugs. In spite of these influences, however satisfactory test-retest reliabilities of
rtt = .65 to .97 (van den Hoed et al. 1981, Zwyghuizen-Doorenbos et al. 1998) have been found.
Another problem of MSLT is the limited external generalization of daytime sleepiness in
everyday situations (Johns 1994). The assumption that the MSLT describe daytime
sleepiness – as reflection of everyday life – Johns (2000) keeps being wrong. As a predictor of
MSLT is therefore not own, regardless how strict standards and criteria were met. In
considering of the relationship between ESS and MSLT are unsatisfactory correlation of
r = .27 (p <.001) or on those that are not significant (Mitler et al 1998.). Reasons for the
inconsistent correlations are different: Either there are satisfactory (significant) correlations
when all patients fell asleep in all MSLT times or when the patients rarely slept or not fell
asleep (Chua et al. 1998).
2.5 Maintenance of Wakefulness Test (MWT)
The Maintenance of Wakefulness Test of Poceta et al. (1992) examines the ability to stay
awake in a sleep-inducing situation. The patient sits in a darkened room on a comfortable
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chair or on the bed and will be asked to refrain movements (e.g., grimacing, shaking), which
may prevent falling asleep to refrain (Hartse et al. 1982, Mitler et al. 1982). Three to four
times a day electrophysiological recordings (C3/A2, C4/A1, EOG and EMG) are recorded in
2-hour intervals of 20 minutes. The earliest start of the first test procedure should be
scheduled two hours after waking. As with the MSLT test history is filmed with a video
camera. Evaluated will be the sleep latency from the moment “light off” until the onset of the
first two epochs of sleep stage 1 or 2.
In various standardization studies, inconsistent cut-off values were found from 13.5 to 18
minutes (Banks et al. 2004, Rühle 2005). Reasons for the different standard values according
to Shreter et al. (2006) are that the test exercises have a significant influence on occasion
staying awake in the test situation. So they provided proof that the sleep latency on the
MWT was deliberately suppressed because the OSAS patients were afraid to get the license
revoked. In considering the relationship between the MWT and ESS were calculated a
satisfactory correlation of r = .48 (p < .001), with the common variance of the two devices
was only 23% (Sangal et al. 1997b).
2.6 Pupillography (Fig. 1)
The Pupillograph Sleepiness Test (PST) from Amtech (Weinheim) reflects the fatigue waves
of the pupil described by Löwenstein. Normally, the pupil size will be constant in normal
central nervous system activation in the dark for a long time. However, occur with increased
daytime sleepiness after a few minutes spontaneous fluctuations (oscillations) on the pupil,
which are recorded with infrared videography. Cause of fluctuations in pupil size is a
mechanism of the autonomic nervous system. With reduced central nervous system
activating two divisions acting simultaneously, which inhibit the Edinger-Westphal nucleus.
This leads to instability of the central sympathetic activation and consequently fluctuating in
an inhibition of parasympathetic activity and the Edinger-Westphal nucleus (Löwenstein et
al. 1963, Yoss et al. 1970).
Fig. 1. Experimental setup for the pupillography. The patient wears an infrared protective
goggle, has propped his chin on a device and looks toward the infrared camera.
Evaluation
The average Pupil Unrest Index (PUI) is the average pupil size fluctuations in millimetres
per second over a period of 11 minutes. Higher PUI values indicate a clinically significant
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daytime sleepiness in (Table 2). In a normal population (n = 349) between 20 and 60 years,
was found a mean value for ln PUI of 1.50 ± 0.39 mm/min. Thus, abnormal values are
obtained from ln PUI > 1.89 and pathological values from ln PUI > 2.28. The cut-off value of
> 6.64 was found for 84.1% of a healthy sample (Wilhelm et al 2001), which was established
that this is independent of gender and age (r = .85 to .94). The PUI correlated low, but
significantly with the subjective estimates of daytime sleepiness in SSS (r = .29,
p < .010). The implementation objectivity and evaluation objectivity seem to be sufficiently
given, because the change in pupil size can be deliberately manipulated. The reliability was
tested in healthy control subjects and is satisfactory (r = .64, p < .001) (Weeß et al. 2000).
Value range Mean-2SD Mean-SD Mean Mean+SD Mean+2SD
ln PUI (mm/min) 0.73 1.11 1.50 1.89 2.28
Percentile 2.3% 15.9% 50.0% 84.1% 97.7%
PUI (mm/min) 2.07 3.05 4.50 6.64 9.80
Table 2. Percentile of the normal reference range for ln PUI and PUI
2.7 Reading test (Fig. 2)
In the first version of the Reading test, it was up to the patients and healthy controls, to select
a passage according to their interests. Therefore, it was possible that the individual level of
activation of OSAS patients may have influenced the excitement level of the books. For this
reason, the story “One day, maybe one night” by Arnold Stadler (2003) was selected. This is
a retrospective narrative. Due to the low excitement level of the narrative it was assumed
that the degree of tonic activation would remain constant.
A B
Fig. 2. In 2A is seen as the patient reads in a semi-recumbent position, the modified form of
the story “One day, maybe one night” by Arnold Stadler (Fischer paperback 2003). In the
face of the electrodes are glued EOG, EEG and the EMG and its right to recognize a
polysomnography. In 2B, the patient is asleep and the book has resigned.
The text was justified, typed in the font “Times New Roman” and the size 12. The pages
were not numbered and included 36 lines with 11 cm length. A lamp (40 watts) was used for
lighting, placed at a distance of one meter above the patient’s head. At the beginning of the
Reading test, the patient was informed by a verbal instruction, to read the text as possible in
the normal reading speed and without interruptions. Patients were asked to keep the book
at a distance of 40 cm. Lack of vision and of reading ability has been excluded by
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spontaneous, aloud reading of few sentences, if the patient was able to read 3-5 sentences
correctly and fluently. About the intention and the period of reading, the patients were not
informed in order to allay apprehensions and expectations.
Evaluation
The reading movements are simultaneous eye movements, which are characterized by either
internal or external amplitude deflections in the EOG. It occurs while reading a specific
rhythm EOG, as the eyes “jump” at the end of the line to the next line start. The reading
movements can be distinguishing well visually by small and big eye movements (Fig. 3). All
reading movements were counted that occurred after a minimum interval of 3 seconds.
Fig. 3. On display are the reading movements of the left and right eye (LEOG and REOG) as
a rhythmic, blue wave pattern. The reading movements occur during reading, when the
eyes “jump” at the line end of the text (right) to line beginning (left). Large eye movements
(e.g. view movements) are characterized by large amplitude fluctuations.
In the present study, the following variables were used and calculated: the average, the
highest and the lowest reading frequency (read line per epoch), sleep latency (in minutes)
and the number of read pages.
Results
The average reading rate of the patients (n = 75) was 7.0 +/- 3.5 lines per epoch. In healthy
volunteers (n = 16) it was 9.4 +/- 4.0 lines per epoch. All healthy subjects were evaluated for
daytime sleepiness than normal, since neither sleep onset tendencies nor decreasing reading
frequencies were observed. In 32 of the 70 OSAS patients (45.5%), however, sleep latency
was found within 60 minutes. Also the reading frequency decreased over time. Rühle and
colleagues calculated for the first time, the sensitivity and specificity of the Reading test,
finding a cut-off value of greater than 11 for a pathological daytime sleepiness (Rühle et al.
2007). The standardized Reading test achieved a sensitivity of 76.2% and a specificity of
66.7% (Erle et al. 2009).
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2.8 Conclusion
2.8.1 Effect size analysis of the Epworth Sleepiness Scale
Rühle and colleagues (2005) researched into an effect size analysis of the ESS the question, if
daytime sleepiness could be investigated through a situation. Therefore, the authors
analyzed the effect sizes of the eight items. From methodological considerations, it was
reasonable to imagine, to come across items with good to very good discriminatory power,
because the ESS has a good to very good reliability and validity.
In the study, which took place in the sleep laboratory of the Helios Clinic in Hagen-
Ambrock, 209 male OSAS patients and 164 healthy subjects participated. To calculate the
effect sizes for each item the difference between of the two item means (of patients and
healthy subjects) was divided by the standard deviation of the normal population. Rühle et
al. received low to very good effect sizes (ES) between 0.19 to 1.50 The best effect sizes were
found for the situation “in reading” (ES = 1.50), “watching TV” (ES = .90), “sit and be passive”
(ES = .85) and for “traffic-related stopping” (ES = .61). Similarly, there was an increased mean
effect size of ES = .88 for the four selected items, compared to a mean effect size of ES = .68 for
the total scale. Some situations of ESS was associated with both healthy subjects and OSAS
patients with a high propensity for sleep, e.g. to “lie down to rest” (ES = .19), as a “passenger”
(ES = .22) and “talk with someone sitting” (ES = .24). For the development of everyday life and
job-related tests – as it had been suggested by Johns (2000), the reading activity was an
important characterisation of daytime sleepiness, because it discriminates at the best between
OSAS patients and healthy individuals in comparison to the other ESS items.
2.8.2 MSLT and MWT criticism
Although MWT and MSLT are often used in practice, since years there is the assumption
that its operationalization does not correspond to the tonic activation. Johns (1998) excludes
that the MSLT is suitable as a predictor of daytime sleepiness in everyday situations,
regardless how strict are implementation and evaluation standards. Although have the
sleep latency on both tests satisfactory correlations as Sangal and colleagues (1992, 1997a)
showed in subjects with various sleep disorders (r = .41, p < .001) and in Narcolepsy patients
(r = .52, p < .001). However, the tests clarify maximum of 20-25% of common variance,
indicating that the test methods measure different constructs of daytime sleepiness. Reasons
for the average correlations according to Sangal et al. (1992) are that patients with
pathological MSLT values were able to stay awake in the MWT, while others who fell asleep
in the MWT were able to stay awake in the MSLT.
In addition, Johns described measurement error as reasons for the variability of individual
test results. It argues that the measurements are depended on the situation character,
internal attitude and physical condition of the patient. Kotterba and colleagues (2007)
reported that the sleep latency of the MSLT corresponds to the individual property to switch
off quickly. In the opinion of John (2000) was the MLST least suitable and is no longer
regarded as the gold standard.
In handling the tests are very time-consuming and labour intensive (because of multiple
tests during the day) as well as it is uneconomical. This would be calling in question the use
of the method (Danker-Hopfe et al. 2006, Johns 2000). Because the claim of a standardized
implementation and evaluation it could also be performed only by professionally-equipped
sleep laboratories (Randerath 1997). Daytime sleepiness can be measured more easily and
possibly more effectively with the ESS (Johns 2000).
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2.8.3 Summary and outlook
Although the MSLT and MWT have been used frequently, in many studies was found
evidence that the reliability and validity of the procedures are unsatisfactory. In addition,
the two test methods don’t correspond to any real life situation (Johns, 2000). Even if it is
objective and standardized measuring instruments, have been repeatedly confirmed
weaknesses in the implementing objectivity of the individual tests as well as their
generalization ability (Danker-Hopfe et al. 2006). John’s criticism is that the reliability and
validity verification of MWT and MSLT were not gone in any way according to objective
and standardized criteria. The ESS compared to the MSLT and MWT has good reliability
and validation criteria, sensitivity and specificity measures. Its only drawback lies in the fact
that the subjective assessments are based on individual perception and trust and the honesty
of the patient.
Johns (2000) emphasizes the need to find an objective test, such as the ESS is valid and able
to quantify the alertness in various everyday situations. Such a test would represent a true
gold standard. Result of this strong criticism and of the clinical relevance of developing a
new measuring method, Rühle et al. (2005) analyzed the effect sizes of the ESS. They
pursued the goal, to detect the daytime sleepiness of life situation as objective, reliable and
valid as possible. The analysis of the ESS and its implications led to the experimental
derivation, design and construction of the Reading test (pilot study: Rühle et al. 2007, main
study: Erle et al. 2009).
2.8.4 Conclusion of the reading test
Both the pilot study and the main study, the alertness impairments in OSAS patients with
the reading activity, a simple spiritual activity were operationalized. In contrast to the MSLT
and MWT daytime sleepiness was not measured in an experimental laboratory situation,
but in an everyday clinical situation. The Reading Test is suitable for the determination of
daytime sleepiness, because it probably produces a low level of attention. The reading
activity will be documented and monitored continuously by EOG. Therefore, the nonreading
phases can be observed, e.g. at the beginning of sleep, movement and looking
around of the patient. In addition, the behaviour spectrum of patients are also detected in
the EMG, as unwanted movements (facial grimacing and head movements), which can
prevent sleep. This aspect would be particularly relevant in experiments.
3. Vigilance and attention in patients with Sleep Apnea Syndrome
3.1 State of research (Fig. 4)
Attention underlies performance of intellectual and everyday tasks. Depending on
requirement character, novelty, intensity and level of activity, different components of
attention are required.
The central nervous system activation (alertness) reflects the degree of general alertness and
represents a kind of basic activation and general responsiveness. It is unconscious, and
affected by the autonomic nervous system and the physiological diurnal state of the
organism. Two variants of the central nervous system activation are described. The tonic
activation is the stable level of attention over a long period of time. A disruption in tonic
activation is manifested by a slowing of cognitive and motor processes. The tonic activation
can be measured with the Multiple Sleep Latency Test MSLT (Carskadon & Dement 1977,
Carskadon et al. 1986), the Maintenance of Wakefulness Test MWT (Poceta et al. 1992) or the
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Pupillography (company Amtech, Weinheim, Wilhelm et al. 1998, 2001). A newer method to
quantify the tonic activation is the Reading test (Erle et al. 2009).
The phasic activation is manifested in stimulus situations, in which short-term increases of the
activation in the resting state are required. Limitations of the phasic activation can result in
delayed reaction rapidities up to omitted reactions. The phasic activation may be tested for
example in the kind of reaction time measurements, e.g. with the test battery of
Zimmermann and Fimm (TAP / 1994), event-related EEG deductions or on the basis of the
heartbeat rate or skin conductivity.
Fig. 4. Proposed relationship between sleep quality and sleepiness-related restrictions
during the day
Sustained attention is the ability to direct attention over a long period to one or more
randomly occurring stimuli and to respond to minimal stimuli changes (Davies, Jones and
Taylor 1984). Vigilance, which is a variant of sustained attention, requires long-term
attention performance in minimally and irregularly occurring stimuli. As reliable indicators
false (i.e. incorrectly or delayed) and omitted responses as well as reaction times can be
measured as an expression of sustained attention and vigilance. Furthermore, particularly in
the field of sleep medicine the Clock Test by Mackworth (1948), modified by Quatember and
Maly (Sturm und Büssing, 1993), and the vigilance test “Carda” by Randerath et al. (1997,
2000) and Gerdesmeyer et al. (1997) and the sustained attention test “Carsim” by Büttner et al.
(2000a/b, 2001) have been used to test the vigilance and sustained attention.
Selective attention is also the ability to focus on specific relevant stimuli and to suppress
simultaneously occurring irrelevant stimuli. The kind of attention function can be
investigated by choice-reaction tasks or orienting responses, e.g. based on the subtest
“Selective attention” to the TAP1.
Divided attention describes the capacity for serial and parallel information processing and the
flexibility of selecting to switch back and forth at least two different sources of information
(Sturm and Zimmermann 2000). Relevant stimuli can each occur in one or two sources of
information to which the person have to respond as quickly as possible. Divided attention can
be measured with dual-task activities (e.g. using the subtest “Divided attention” of the TAP).
As with many sleep-related disorders, such as hypersomnias and dyssomnias, the victims
suffer from, in addition to their nocturnal symptoms, increased daytime sleepiness and the
tendency to fall asleep (Büttner et al. 2004b). These difficulties are in turn associated with
attention-related deficits and limitations (including Gerdesmeyer et al. 1997, Müller et al. 1997,
Randerath et al. 1997, 1998, Weeß 1997, Weeß et al. 1998a/b, Büttner et al. 2003b, 2004b).
1 TAP = German: Testbatterie zur Aufmerksamkeitsprüfung; English translation: Test battery for
Attentional Performance
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Consequence of this reduced performance include an increased risk of accidents at work
and in traffic and thus a higher socio-medical risk (e.g. Bradley et al. 1985, Podszus et al. In
1986, He et al. 1988, Mitler et al. 1988, Lamphere et al. 1989, Roehrs et al. 1989, Bédard et al.
1991, Kribbs et al. 1993a/b, Gerdesmeyer et al. 1997, Randerath et al. 1997, 1998, Weeß 1997,
Weeß et al. 1998a/b, Büttner et al. 2000a/b, Büttner 2001).
To explore the difficult relationship between sleep, daytime fatigue and physical and mental
performance is based mainly on three conditions (Johnson 1982, Weeß 1997, Weeß et al.
1998a/b). Thus, the three mentioned above parameters will be affecting through a variety of
other variables, for example by the motivation of the healthy subjects or patients, or the
daily and weekly rhythm. Furthermore, daytime fatigue and performance as well as their
underlying attention-related processes are complex constructs. This analysis will be
complicated also by the lack of standard term uses in the medical and psychological
literature (Johnson 1982, Weeß 1997, Weeß et al. 1998a/b).
There are, both in the medical and especially in sleep medicine research, a number of
different research approaches and definitions regarding the attention and attention-driven
processes (Rützel 1977, Rapp 1982, Brickenkamp & Karl 1986, Posner & Rafal, 1987, Säring
1988, Posner & Petersen, 1990, Posner 1995), which accentuate different characteristics and
aspects of the daytime performance (James 1890, Head 1926, Mackworth JF 1956,
Mackworth N 1958, Schmidtke 1965, Norman 1973, Bäumler 1974, Harnatt 1975, Rützel
1977, Brickenkamp & Karl 1986, Posner & Rafal, 1987, Säring 1988, Posner & Petersen, 1990,
Rollet 1993, Schmöttke & Wiedl 1993).
Currently, in the sleep medicine literature, mainly the concept of Posner and Rafal (1987)
will be used (Keller et al. 1993, Weeß 1997, Weeß et al. 1998a/b).
Also problematic are the very diverse conducted empirical analysis of attention and its
components and the varying quality of the validation test procedures and instruments.
Thus, inter alia vigilance covered by inappropriate (Stephan et al. 1991), too complex
(Bédard et al. 1993) or timely too short (Bédard et al. 1991, 1993) test requirements (Weeß
1997, Weeß et al. 1998a/b).
To capture the tendency to fall asleep in Obstructive Sleep Apnea is conducted usually by
the MSLT (Multiple Sleep Latency Test) (Poceta et al. 1992), because it correlated most
strongly with the subjective state/mood of OSAS. However, through it the attention and
vigilance will be detected only indirectly (Denzel et al. 1993).
For this purpose researched Denzel et al. (1993) for more suitable methods and examined in
this context, two computerized neuropsychological test procedures, a vigilance and a
attention test, in which the attention test was checked under three experimental conditions
(visual, auditory, combined). In both the dual-task-task as well as the vigilance testing was
found significant differences before and after nCPAP therapy (Denzel et al. 1993).
Similar results – i.e. a significant improvement of vigilance under nCPAP – were found
already by Kesper-Schwarzenberger et al. (1991), Cassel et al. (1991) and George et al. (1997;
DADT)
As important criteria was found the standardization of experimental conditions (Horn et al.
1983, Denzel et al. 1993) and the design of the experimental setup (the author). Thus
showed, inter alia, that an immediate auditory feedback about the correctness improved the
occurred reactions improved the motivation of the patients, thereby obscuring the effects of
sleep deprivation and their resulting poor performance (Wilkinson 1961, Steyvers &
Gaillard 1993, Weeß 1997, Weeß et al. 1998a/b).
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3.2 Vigilance test Carda (Fig. 5)
The Ambrock vigilance test “Carda” by Randerath et al. (1997) recorded the vigilance
performance over a period of 30 minutes. The patient sits in a semi-darkened room in front
of a black computer screen and look at the picture of a street with a running road median
and the lateral lane boundaries. They are asked to respond within one second of a with a
computer keyboard button on stimuli (white flashing rectangles), which occur in time and
space for 20 ms randomly. In each 10-minute interval 100 stimuli appearing, in the total
period 300 will be shown. After a brief instruction and a short practice the test is started via
a menu driven DOS computer program.
Fig. 5. Driving Simulator Carda by Gerdesmeyer et al. 1997, Randerath et al. 1997, 1998
Evaluation
Right and false reactions are calculated in relation to the presented events (in percentage),
the latter being registered as an error. The unfounded (delayed) reactions are given in
absolute numbers. The age-and gender-independent cut-off value for the error is 5.75% (SD
= 11.3%) after a standardization study with healthy volunteers of Randerath and colleagues
(2000). For the unfounded responses and response times are currently no cut-off values.
Measurements for the reliability and validity are pending.
3.3 Sustained attention test Carsim (Fig. 6)
The Ambrock sustained attention test “Carsim” by Büttner et al. (2000a/b, 2001) recorded
its performance over a period of 30 minutes. The image with a road median and lane
boundary is simulated polychrome. On the right side of the road obstacles (in the kind of
no entry signs) can be presented, which are only briefly visible in each case (e.g. for 200
ms). Their appearance is timely random, in which a fixed number of events can be
adjusted with a 5-minute section. The patient now has the task to keep up with the help of
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a steering wheel in his lane the ideal track (tracking) and by using of two buttons (both
same function), which are located on the steering console, to respond on appearing
obstacles (visual search).
Fig. 6. Driving Simulator Carsim by Büttner et al. 1999, 2000
Evaluation
Depending on the steering wheel movements, the position of the vehicle on the road will be
recalculated and visualized on-line. The program records the time deviation from the ideal
line (tolerance deviation time) and of the lane (tracking deviation time) and the right, the
missing, the unfounded reactions and the reaction time (Büttner et al. 2000a/b, Büttner
2001). Tolerance or track deviation is the number of tracking errors, which in absolute terms
described, exceeds the tolerance and lane width in the test. By converting the number of
pixels we obtain the time in seconds, which was driven outside the tolerance range or
beyond the roadway.
Standardization and quality criteria
The average error of the tracking deviation time was 2.3 ± 4.5 s in the calibration sample, the
limit of the track deviations of healthy persons in a 95% confidence interval was < 13.2 s,
98% of healthy individuals have had values between 0 to 150 track deviations. The mean
error of tolerance deviation time was 96.0 ± 177.0 s in the healthy person’s, the limit of
tolerance deviations of the calibration sample in a 95% CI was < 450.4 s (Büttner et al.
2000a/b, Büttner 2001).
The verification of the reliability using the Cronbach alpha was for the tracking component
r = .9785, for the visual search r = .9666 and for the reaction time = .8943. The verification of
the test-retest reliability (after 3 days) was for the tracking component rtt = .9855, for the visual
search rtt = .9447 and for the reaction time rtt = .9211 (Büttner et al. 2000a/b, Büttner 2001).
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3.4 Sustained attention test Quatember & Maly (Fig. 7)
With the computerized sustained attention “Clock test” of Quatember and Maly (Wiener
Testsystem TM, Schufried, Austria 1994; modified for Task force Vigilance and SIESTA group
of DGSM2) the sustained attention will be evaluated under monotone conditions and the
processing diligence will be measured in the kind of errors and reaction times over a period
of 60 minutes. There are two types of errors: missed and incorrect (delayed) responses
reactions. Patients are instructed to press a key on the computer keyboard when the
“moving point” in a points circle one point skips. At the beginning of the test will be started
shortly to introduce the circular arrangement of points. During implementation, the patients
sit in a relaxed position ca. 60-80 cm in front of the screen in a semi-darkened room.
Evaluation
The average reaction rate (in milliseconds), the degree of right, incorrect and omitted
responses were recorded at Q&M-sustained attention test.Danker-Hopfe, Sauter and Popp
(2006) determined in a standardization study with healthy volunteers cut-off values of more
than 3 for omitted responses, more than 4 for incorrect responses and longer than 498
milliseconds for the response times of subjects. Standard values for OSAS patients are not
yet available.
Fig. 7. Sustained attention test by Quatember and Maly (1994)
3.5 Conclusion
The driving simulator Carda, similar to the test developed by Findley, does not fulfil the
requirements that are important on a real tracking test. It is rather a reaction test, which
describes the attention and the vigilance.
Krieger et al. (1997) were able to demonstrate by means of questionnaires that the accident
rate in OSAS patients was often caused by sleepiness and that both the rate of accidents and
2 DGSM = Deutsche Gesellschaft für Schlafforschung und Schlafmedizin (engl.: German Society of Sleep
Research and Sleep Medicine)
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nearly accidents could be reduced with nCPAP therapy. A test for assessment of accident
risk would therefore be helpful.
Findley was found a correlation between the number of accidents and the error rate in a
driving simulator test using Steer Clear and data’s of Accidents Authority Virginia/USA. He
also had verified a certain connection between accident rate and Sleep Apnea Syndrome and
a dependence on the severity of the disease (Findley et al. 1989, 1995, 1999, 2000). Tests of
this kind should be used only with great caution on the question of driving ability, because
it detected only a few aspects.
Due to the simple construction Steer Clear and Carda offer also some advantages, because the
technical effort is relatively low and even restricted patients can understand the task very
well. However, the tests can only evaluate the response to nCPAP treatment in cases with
much higher error rate and can control it course.
Carda Carsim
Monotony (+) +++
Continuity – ++
Interactivity – +++
Usability +++ ++
Table 3. Design and properties of the two simulation programs
The severity of sleepiness, as assessed by the ESS, didn’t correlate with the results of driving
simulators. Sleepiness/drowsiness describes the degree of alertnes and will be influenced by
central nervous system activation (Weeß et al. 2000). Because the test situation, the
sleepiness is often compensated in moderate limitations (ESS < 13) – in our patients, the ESS
score was on average = 11.0 – so that the error rate or track deviation showed no relevant
dependence. However, in OSAS patients with profound sleepiness (ESS score > 13) a higher
number of errors were found in Carda reached a higher (Randerath et al. 2000).
Under the testing with Carsim, the number of patients who have had a pathological
deviation is much higher. The complex task of interactive driving simulation recorded thus
patients with reduced performance, special with difficulties in the divided attention and
interactive activities. This could be proven, to persons whose driving performance was
checked after alcohol administration with a driving simulator. In OSAS capacity was similar
limited to persons with a blood alcohol of 95  25 mg/dl (George et al. 1996a).
Studies, which correlate the laboratory results of tracking tests with the real frequency of
accidents, are still missing. It would be therefore desirable to obtain objective data on road
authorities to characterize better any risk patients with this sensitive instrument. A trackingdriving
simulator has a higher reality character than a reaction test, because it realized better
the task, i.e. the reflection of driving situation (George 2000). Yet here, too, it is important to
be sceptical about its evidence power, because the driving performance is dependent of
many factors (e.g. responsible acting), which cannot be detected alone by simulation tests. A
driving simulator test should be used only as one of several components in the complex
assessment of driving ability.
The interactive driving simulator test Carsim, designed by the Ambrock task force, can also
be used for further questions: In OSAS patients may be improve due to different treatment
modalities several sub-components of attention (such as selective attention, divided
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attention, sustained attention, processing speed) (Büttner et al. 2000a/b, Büttner 2001). An
interactive driving simulator should reflect several of these changes and should be a more
suitable instrument, because tracking tasks reflect more components of the limited
capabilities in comparison to reaction tests (Carda).
We could demonstrate that an interactive driving simulator (e.g. Carsim) describes the disorder
of OSAS patients more sensitive. It is used, therefore, specifically in clinical trials for the
assessment of treatment effects to attention increase (e.g., nCPAP or theophylline (Büttner et
al. 1999 or 2003a, 2004a)).Due the easy use also Carda will continue to be a suitable method to
detect neuropsychological disorders and demonstrate treatment effects in clinical routine.
4. Memory processes in patients with Sleep Apnea Syndrome
4.1 State of research
Jenkins & Dallenbach (1924) could show for the first time that learning tasks which are
presented before sleep could be keep better than tasks that are presented before
wakefulness. This was confirmed in other studies (Hennevin et al. 1995, Smith 1996). The
discovery of REM sleep (Dement & Kleitman 1957) was the start for a more specific research
program in which certain stages of sleep each were assigned specific roles for the memory
processes. As follow on one hand, REM sleep, was attributed partly memory-favouring
effects because of its particular physiological changes, on the other hand, as well as the Slow
Wave Sleep (SWS) was attributed the same effects (Hobson & McCarley 1977, Crick 1983,
Wilson & McNaughton, 1994, Karni et al. 1994, Squire & Alvarez 1995).
One of the studies on cognitive deficits in the thinking, memory, communication and the
ability to learn new information in OSAS patients comes from Kales (1985). In this study
76% of OSAS patients show cognitive deficits in all these areas. A study by Naëgelé et al.
(1995) showed that the executive functions, which are important for the acquisition of
information during memory processing in OSAS patients, were impaired.
It is assumed that in sleep disorders the often found reduced sleep quality leads, as a result
of Slow Wave Sleep or REM suppression, increased nocturnal arousal responses or
prolonged awakenings to a reduced recovery function of night sleep (Weeß et al. 1998a/b).
According to Jennum et al. (1993), Insomnia and sleepiness affect cognitive functions.
Patients with excessive daytime sleepiness complaints have special problems in situations of
physical relaxation and during long monotonous concentration tasks (Schwarzenberger-
Kesper et al. 1987).
Cassel et al. (1989) were able to detect in Sleep Apnea patients a reduced cognitive
performance and a decreased non-verbal processing speed. In this connection they were
able to detect a reduced cognitive processing speed on ZVT in OSAS patients. Also Kotterba
et al. (1997) detect in 32 of 40 OSAS patients abnormal results on the ZVT. In another study
of Kotterba et al. (1998), they found in OSAS patients an impairment of the central nervous
system activation (alertness), of the selective attention and of the sustained attention. Barbé et
al. (1998) verified in Sleep Apnea patients a decreased vigilance.
4.2 Number-connection test (ZVT)
The number-connection test is composed from four number matrices. Each matrix contains
90 unsorted numbers. It must be connected according to the statement by lines from 1 to 90.
For estimating the test processing time, the experimenter uses a stopwatch.
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The test is used to measure the basal, all intelligence performances underlying, largely
milieu independent and genetically related cognitive performance speed. It corresponds
with those ability bundles, which in literature will be called as “liquid” intelligence,
“perceptual speed” or “processing speed” are. The test has a wide range of applications. It can
apply from 8th years up for all age levels; from the special school to high school and
universities (for all levels of education). It is very economical and can be use on an
individual or group test. For the processing of the tests the subjects require 5 to 10 minutes
(Oswald and Roth, 1987).
The high reliability of the test (test-retest reliability between rtt = .84 and rtt = .973; parallel
test reliability between r = .95 and r = .98) is largely independent of age and educational
level of the subject. The correlations with various intelligence techniques (PSB, HAWIE, IST-
70, RAVEN, CFT-3) are between r = .40 and r = .83. For the individual experiments exist
currently standards for 8th to 60th years (n > 2,000), standard values for the group version of
the ZVT are available for the age range from 9 to 16 years. The mean of the norm sample
(16-60 years) is a T-value of 50 ± 10.The Sleep Apnea patients achieved before therapy a Tvalue
of 39.82 ± 10.73, under a only 3-day-CPAP therapy, there was a significant
improvement (T-value: 43.08 ± 10.50) (Büttner et al. 2007).
4.3 Benton Test
The Benton Visual Retention Test is one of the best known and most widely used tests of
immediate remembering for visual-spatial stimuli. The test consists of three parallel series,
each with 10 geometric stimulus cards. The test person or the patient is shown one stimulus
card for a short time (10 seconds), the figure of the card is to be draw directly after showing
or after a short delay as accurately as possible. Further testing variations allow a shorter
presentation time from 5 seconds, direct copying or simply selecting/choosing of a seen
template from four alternatives. The drawing form allows evaluating, especially in children,
the assessment of the draw ability, whereas the electing/choosing form evaluates the memory
without the drawing component. The German edition follows the fifth American edition of
1992. It contains a simplified scoring system, additional evaluation examples, advanced
standard values and a summary with new findings (Benton test at the onset of dementia).
The German Benton also contains, in contrast to the U.S., the election form. The numerous
new German-published studies for the Benton test were specifically considered. The test is
used in adults until an old age and in children older than 7 years (Benton 1974).
Retest reliability for the drawing form is rtt = .854. The relationship between drawing form and
electing/choosing form is relatively low (r = .55). There are numerous studies, especially in the
3 This retest reliability has been verified by the authors of the following sources:
1. http://www.google.de/search?q=cache:5m0-sgoxY1AJ:wt.fb3.uni-wuppertal.de/fachschaft/
psychologie/studi_hilfen/files/Hauptstudium/Diagnostik/Zahlen-Verbindungs-Test_(ZVT).
doc++reliabilit%C3%A4t+zvt+test+&hl=de&lr=lang_de&ie=UTF-8: (rtt = .81) and
2. http://www.testraum.ch/Serie%204/ZVT.htm: (rtt between .81 and .97).
Learning effects of the ZVT may thus be concluded in clinical trials.
4 This retest reliability has been verified by the authors of the following sources:
1. http://www.testzentrale.de/tests/t0300401.htm: Retest reliability for the drawing form was rtt = .85
2. http://www.unifr.ch/ztd/lernsystem/tb/benton.html#Testentwicklung: Retest reliability for the
drawing forms C, D and E is given as average of rtt = 0.85.
Learning effects of the Benton test may thus be concluded in clinical trials.
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evaluation of brain damage.The mean of correct reproductions of the 15-44-year old persons
was 8 (IQ score of 95-109). In contrast, the mean of the OSAS patients was 6.76 before
therapy (IQ score: 70-79), after a 3-day treatment with nCPAP it was 7.84 (IQ score: 80-
94).The mean of error numbers of 15-39-year-old persons was three (IQ score of 95-104). The
error mean of the study patients was 4.46 before therapy (IQ score: 90-94), after 3-day
treatment with nCPAP it was 2.66 (IQ score: 105-109) (Büttner et al. 2007).
4.4 Conclusion
As mentioned above, in several studies could be demonstrated neuropsychological and
cognitive deficits in OSAS patients (Bédard et al. 1991, Naëgelé et al. 1995, Gresel et al. 1996,
Engleman et al. 2000). This allowed finding inter alia differences between healthy subjects
and OSAS patients in the assessment of cognitive processing speed and of performance
speed (ZVT) (Cassel et al. 1989, Kotterba et al. 1997, Büttner et al. 2007). Also in the Benton
test to record the performance of visual memory the OSAS patients showed – compared
with healthy subjects – significantly worse results in the number of errors. None significant
results were found for the number of correct reproductions. This may have resulted through
the sample composition or sample size. On the other hand, it could be that the increased
error number and the nearly normal number of correct responses is a criterion or a feature
for the detection of neurocognitive deficits in OSAS patients (Büttner et al. 2007).
Conclusion
It can be said that OSAS patients differ from healthy individuals with respect to cognitive
skills. These differences can be verified both the memory processes (Benton) and in
cognitive processing speed and performance speed (ZVT). These impairments can have
serious consequence, if or as long as they remain untreated.
4.4.1 CPAP therapy and its effect
In various studies improved performance under nCPAP therapy have be determined
regarding to changes in neuropsychological parameters and/or test performance. Lamphere
et al. (1989) could be shown that after one therapy night there was a significant
improvement of the attention, which normalized after 14 days of nCPAP. In several studies
it could be detected also a reduction in both subjective and objective daytime sleepiness
(Montplaisir et al. 1992, Engleman et al. 1993, 1994, Douglas et al. 2000 – according to
Schwarzenberg-Kesper et al. (1987) is the improvement of daytime sleepiness an essential
motif for a good therapeutic compliance of the patients). Sforza et al. (1995) found after one
year of nCPAP treatment an objectively reduced daytime sleepiness, which increased again
after a night of therapy interruption. In several studies could be verified also improved
further neuropsychological deficits. Kotterba et al. (1998) reported a significant
improvement in the simple attention as well as the divided attention, in the cognitive
performance and the processing speed. The latter could be replicated also by Büttner et al.
(2007). Even an improvement of vigilance or sustained attention, and various cognitive
deficits due to the nCPAP therapy was described many times (Denzel et al. 1993, Engleman
et al. 1994, Randerath 1997, 2000, Büttner 1999).
Other studies have shown, however, that the cognitive and neuropsychological deficits
don’t increase or only improving in certain areas, which could indicate an irreversible
hypoxic damage of the CNS (Montplaisir et al. 1992, Bédard et al. 1993, Kotterba et al. 1998)
and thus point up the importance of early diagnosis and treatment of OSAS underscores.
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Conclusion
The difference or the improvement after effective nCPAP therapy suggests the need to use
this therapy in OSAS patients, possibly to avoid serious impairment in the memory
processes and in cognitive performance or to allow the patient not to suffer under the
daytime consequences of Sleep Apnea Syndrome.
5. Summary
In the western and eastern industrial countries, the number of sleep disturbed subjects
increased over the time. Undiagnosed and untreated, sleep disorders caused on one hand
often by subjective suffering among those affected individuals and on the other hand, due to
decreased attention and increased daytime fatigue or daytime sleepiness, to an increased
risk of accidents in road traffic and workplace (e.g. Peter et al. 1995, Gerdesmeyer et al. 1997,
Randerath et al. 1997, 1998, Büttner et al. 2000a/b).
Sleep Apnea syndromes are common disorders. 1-5% of the population is affected by it (men
are about ten times more affected than women). In particular, patients with OSAS suffer in
addition to their symptoms often also on a multitude of sequelae, including excessive
daytime sleepiness (Büttner et al. 2004e), vigilance decrease (Büttner et al. 2003b, 2004c) and
memory disorders (Büttner et al. 2003c/d).
These performance restrictions or impairments affect the affected subjects, both
professionally and in their ability to drive motor vehicles (Findley et al. 1988a/b, 1989b,
1990, 1991, 1995, Mitler et al. In 1988, Cassel et al. 1991a/b, 1993, 1996 , ATS 1994,
Gerdesmeyer et al. 1997, Krieger et al. 1997, Randerath et al. 1997, 1998, 2000, Weeß 1997,
Weeß et al. 1998a/b, Büttner et al. 2000a/b, Büttner 2001). Consequences of this reduced
performance are therefore often accidents or nearly accidents by falling asleep at the wheel.
However, other cognitive and mental functions and the quality of life can be affected by
sleep disorders (Sleep Apnea Syndrome, Insomnia and/or Narcolepsy).
In summary therefore, can be said that sleep disorders and/or sleep diseases are complex
disorders which human beings can affect in his totality and in his whole personality. It can
therefore affect all physical, mental and spiritual processes. It can lead to lower physical and
mental performances; reduce vigilance, impaired attention and concentration. It can affect
the quality of life, reduce, limit and/or prevent social contacts and competencies skills, and
cause in other psychiatric5, neurological6 and organic7 diseases.
A detailed sleep diagnostics and possibly therapy of previously known sleep disorders
and/or sleep diseases is therefore essential to prevent complications and comorbidities, to
prevent treatment resistance with respect to other physical and mental diseases and to
provide effective medical treatment.
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Sleep Disorders
Edited by Dr. Chris Idzikowski
ISBN 978-953-51-0293-9
Hard cover, 190 pages
Publisher InTech
Published online 14, March, 2012
Published in print edition March, 2012
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For progress to be maintained in a clinical field like sleep medicine, unimpeded, unrestricted access to data
and the advances in clinical practice should be available. The reason why this book is exciting is that it breaks
down the barriers to dissemination of information, providing scientists, physicians, researchers and interested
individuals with a valuable insight into the latest diverse developments within the study of sleep disorders. This
book is a collection of chapters, which can be viewed as independent units dealing with different aspects and
issues connected to sleep disorders, having in common that they reflect leading edge ideas, reflections and
observations. The authors take into account the medical and social aspects of sleep-related disorders,
concentrating on different focus groups, from adults to pregnant women, adolescents, children and
professional workers.
How to reference
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A. Büttner(-Teleaga) (2012). The Effects of Sleep-Related Breathing Disorders on Waking Performance, Sleep
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http://www.intechopen.com/books/sleep-disorders/the-effects-of-sleep-related-breathing-disorders-on-wakingperformance

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