PEDIATRICS
Adenotonsillectomy Improves Neurocognitive Function in Children with
Obstructive Sleep Apnea Syndrome
Bat-Chen Friedman, MD1; Ayelet Hendeles-Amitai, BA2; Ely Kozminsky, PhD2; Alberto Leiberman, MD3; Michael Friger, PhD4; Ariel Tarasiuk, PhD5; Asher Tal, MD1
1Department
5Sleep-Wake
of Pediatrics B, 2Department of Education, 3Department of Otolaryngology, 4Department of Epidemiology, Faculty of Health Sciences,
Disorders Unit, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel
Objective: To evaluate neurocognitive functions of children with obstructive sleep apnea syndrome (OSAS), before and after adenotonsillectomy,
compared with healthy controls.
Design: Prospective study.
Patients and Methods: Thirty-nine children with OSAS aged 5 to 9 years
(mean age, 6.8 ± 0.2 years) and 20 healthy children (mean age, 7.4 ± 1.4
years) who served as controls, underwent a battery of neurocognitive
tests containing process-oriented intelligence scales. Twenty-seven children in the OSAS group underwent follow-up neurocognitive testing 6 to
10 months after adenotonsillectomy. Fourteen children in the control
group were also reevaluated 6 to 10 months after the first evaluation.
Results: Children with OSAS had lower scores compared with healthy
children in some Kaufman Assessment Battery for Children (K-ABC) subtests and in the general scale Mental Processing Composite, indicating
impaired neurocognitive function. No correlation was found between neurocognitive performance and OSAS severity. Six to 10 months after adenotonsillectomy, the children with OSAS demonstrated significant
INTRODUCTION
OBSTRUCTIVE SLEEP APNEA SYNDROME (OSAS) IS A COMMON PEDIATRIC DISORDER AFFECTING UP TO 2% OF CHILDREN AGED 2 TO 8 YEARS.1 Sleep of children with OSAS is characterized by frequent apneas and hypopneas, intermittent hypoxemia, and
sleep fragmentation due to numerous arousals and awakenings. In children, OSAS may result in significant clinical consequences, including
growth retardation,2 right and left ventricular dysfunction,3,4 and behavior and learning problems.5-8 There is increasing evidence to support an
association between OSAS and attention-deficit/hyperactivity disorder
(ADHD).6 Previous studies have shown a nearly 3-fold increase in
behavior and attention abnormalities in children with sleep-disordered
breathing.6,9-11 There is also increasing evidence that children with
OSAS suffer from impairment of neurocognitive functions.7,8,12
Adenotonsillar hypertrophy is the most common cause of OSAS in
otherwise healthy children. Adenotonsillectomy results in significant
improvement in clinical as well as polysomnographic parameters.13-15
Behavior problems and quality of life tend to improve after adenotonsillectomy and resolution of the sleep-disordered breathing.11,16
Improvement in learning and behavior has been reported following
treatment of OSAS in children.7,11,16,17 However, the report that young
children who snore frequently and loudly during sleep are at greater risk
for poor academic performance in later years, even well after snoring has
Disclosure Statement
Supported by Grant No. 89914102 from the Chief Scientist, Ministry of Health,
Israel.
Submitted for publication May 2003
Accepted for publication September 2003
Address correspondence to: Asher Tal, MD, Department of Pediatrics B, Soroka
University Medical Center, Faculty of Health Sciences, Ben-Gurion University of
the Negev, PO Box 151, Beer-Sheva 84101, Israel; Tel: 972-8-640-0656 or 97264-600-554; Fax: 972-8-628-7163; E-mail: [email protected]
SLEEP, Vol. 26, No. 8, 2003
999
improvement in sleep characteristics, as well as in daytime behavior. Their
neurocognitive performance improved considerably, reaching the level of
the control group in the subtests Gestalt Closure, Triangles, Word Order,
and the Matrix analogies, as well as in the K-ABC general scales,
Sequential and Simultaneous Processing scales, and the Mental
Processing Composite scale. The magnitude of the change expressed as
effect sizes showed medium and large improvements in all 3 general
scales of the K-ABC tests.
Conclusions: Neurocognitive function is impaired in otherwise healthy
children with OSAS. Most functions improve to the level of the control
group, indicating that the impaired neurocognitive functions are mostly
reversible, at least 3 to 10 months following adenotonsillectomy.
Key Words: Sleep apnea, neurocognitive function, adenoids and tonsils.
Citation: Friedman BC; Hendeles-Amitai A; Kozminsky E et al. Adenotonsillectomy improves neurocognitive function in children with obstructive
sleep apnea syndrome. SLEEP 2003;26(8):999-1005.
resolved,8 suggests that the neurocognitive deficits may be only partially reversible after treatment.
Although awareness of the deleterious effect of OSAS on neurocognitive function is well established, only a few prospective pediatric studies have examined neurocognitive functions before and after treatment.7,11,12 The purpose of the present study was first to evaluate specific neurocognitive functions of children with OSAS compared with
healthy controls and then to evaluate the effect of adenotonsillectomy on
the neurocognitive functions of these children.
METHODS
Subjects and Study Design
Children aged 5 to 9 years known to have OSAS who were candidates
for adenotonsillectomy because of sleep-disordered breathing, were
recruited to the study from the pediatric sleep laboratory and from the
pediatric otolaryngology outpatient clinic of the Soroka University
Medical Center. Children were consecutively recruited if they were
between 5 and 9 years of age and spoke fluent Hebrew because the available neurocognitive tests are validated for Hebrew and this age group.
Children with chronic lung diseases, neuromuscular or heart diseases, as
well as children with ADHD or other diagnosed psychiatric or developmental disorders were excluded from the study. Healthy children
matched by age, sex, and socioeconomic status were recruited from the
same education institutes as a control group. Sleep-disordered breathing
was excluded in the control group by sleep questionnaires (controls did
not undergo polysomnography). After their parents signed informed
consent, all children underwent a series of neurocognitive tests that were
presented to them at home by a trained psychologist, and their parents
filled out a sleep questionnaire. Those children who underwent adenotonsillectomy were reevaluated 6 to 10 months after the operation, using
the same set of neurocognitive tests (Figure 1). Since previous exposure
to neurocognitive tests can improve the way a person functions in the
test-retest,18 children (of both the OSAS and control groups) were evalNeurocognitive Function in Sleep Apnea—Friedman et al
uated twice in order to cancel this learning effect. The institution’s ethics
committee approved the study protocol.
For school-aged children, Word Order measures this recall ability both
with and without an interference task. This task assesses several skills:
auditory-visual integration, auditory-motor memory, and retention without rehearsal.
The Simultaneous Processing Scale represents the subtests in which
input has to be integrated and synthesized simultaneously to produce the
appropriate solution. It includes 4 subtests: (1) Gestalt Closure measures
the child’s ability to “fill in the gaps” in a partially completed drawing
and to name or describe that drawing. This task measures the following
skills: perceptual closure, perceptual inference, and conversion of
abstract stimuli into a concrete object; (2) Triangles measures the child’s
ability to assemble several identical rubber triangles to match a picture
of an abstract design; this task measures nonverbal concept formation;
(3) Matrix Analogies measures the child’s ability to select the picture or
design that best completes a 2-by-2 visual analogy; this task assesses
analytic thinking; and (4) Spatial Memory measures the child’s ability to
recall the location of pictures arranged randomly on a page; this task
assesses immediate recall and spatial localization.
Mental Processing Composite is a combination of the Sequential and
Simultaneous Processing Scales and is intended as the measure of total
intelligence in the assessment battery. The K-ABC provides individual
scores for each subtest, total scores for both Sequential and
Simultaneous Processing Scales, and a score that combines both, the
Mental Processing Composite.
Verbal Intelligence was assessed using the Vocabulary subtest from
the Wechsler Intelligence Scale for Children (WISC-R 95).22 The
Vocabulary subtest consists of 25 words arranged in order of increasing
difficulty. The child is asked to explain orally the meaning of each word.
The task reflects the ability to learn and accumulate information and provides an estimate of intellectual capacity. Performance on this subtest is
stable over time and relatively resistant to neurologic deficit and psychologic disturbance.22 Vocabulary is the most reliable subtest (r = .86)
in the verbal scale of the WISC-R95.22
Sleep Questionnaire
A subjective report about sleep characteristics was obtained using a
questionnaire that was filled out by the parents at the first meeting and
again at the second meeting, 6 to 10 months later. The questionnaire consisted of a total of 26 questions about the sleep behavior of the child. We
chose questions based on questionnaires used in previous studies.6,7,19
The parents were asked to rank the occurrence of several sleep characteristics on a scale of 0 to 4: 0-never, 1-seldom, 2-sometimes, 3-often, 4almost every night. The other part of the questionnaire included questions about socioeconomic status, general health, and daytime behavior
of the child (Appendix).
Neurocognitive Assessment
All subjects were tested at their homes between the hours of 2:00 PM
and 6:00 PM by qualified testers. The testers were not involved in the
process of treatment and recruitment of the children, were blinded to the
child’s diagnosis (OSAS or control), but were not fully blinded to the
repeated test because the same tester performed both evaluations for
each child. The chosen battery was based on the Kaufman Assessment
Battery for Children (K-ABC). The K-ABC is the only intelligence test
that has valid norms for Israeli children20 between the ages of 3 to 13
years, namely, is appropriate for the range of the subjects’ ages. In addition, the test is child oriented with colorful and game-like materials,
which aid in maintaining rapport with the children.
The K-ABC intelligence scales are process oriented; they focus on
whether the stimuli are manipulated 1 at a time or simultaneously,
regardless of item content.20,21 The test contains 3 scales: 2 scales of
mental processing—sequential and simultaneous—and an achievement
scale. Each scale contains several tests. The present research battery
included only the Mental-processing Scales that measure problem solving in novel situations. The Achievement Scale was excluded because it
intends to assess factual knowledge and skills and not pure cognitive
functioning. In addition, the manual of the K-ABC enables the exclusion
of 1 test of each scale while maintaining a valid score. In order to shorten the assessment duration, we excluded 1 subtest of each scale.
The Sequential Processing Scale represents tasks (subtests) in which
problems are solved by arranging the input in sequential or serial order.
All of these tasks measure short-term memory characteristics. This scale
includes subtests: (1) Number Recall, which measures the child’s ability
to repeat, in sequence, a series of numbers spoken by the examiner. This
task measures automatic auditory-vocal memory and (2) Word Order,
which measures the child’s ability to point to silhouettes of common
objects in the same order as those objects were named by the examiner.
Polysomnography
The polysomnography (PSG) study was performed using a computerized commercially available sleep-monitoring system (SensorMedics
Inc, Yorba Linda, Calif, USA) and streamed through to an optical disk
for later analysis. The PSG was performed as previously described.2
Scoring
Scoring was done by a trained technician and reviewed by a trained
polysomnographer. Sleep-wake and sleep stages were scored according
to Rechtschaffen and Kales criteria.23 Arousals and awakenings were
scored using the American Sleep Disorders Association criteria24 with
appropriate modifications for children.25 The arousal index was calculated as the number of arousals per hour of sleep.
Obstructive apneic and hypopneic events were scored according to the
recommended pediatric criteria of the American Thoracic Society.26
Obstructive apnea was defined as paradoxical breathing for at least 2 respiratory cycles with complete cessation of nasal airflow (airflow reduction of at least 80%). A hypopnea was scored when the paradoxical
breathing was accompanied by a reduction of at least 50% in airflow,
resulting in either an arousal or in oxygen desaturation of at least 4%.
The respiratory disturbance index (RDI) was calculated as the number of
respiratory events (apneas + hypopneas) per hour of sleep. The oxygen
saturation variables included mean and nadir SaO2 and the desaturation
index (the number of desaturation events [SaO2 decrease of at least 4%]
per hour of sleep). The diagnosis of OSAS was based on a history of
snoring, difficulty in breathing during sleep, and apnea witnessed by parents in children with obvious hypertrophied adenoids and tonsils with an
RDI of at least 1 per hour. When the clinical diagnosis of OSAS was
obvious (sleep questionnaire and physical diagnosis) and associated with
kissing tonsils, PSG was not done. The need for adenotonsillectomy was
determined by the pediatric otolaryngologist (AL) based on both clinical
Figure 1—Study protocol of the evaluation (sleep questionnaires and cognitive functions)
and treatment stages. In 26 of the 39 children with obstructive sleep apnea syndrome
(OSAS), the first diagnostic evaluation included polysomnography. T&A refers to adenotonsillectomy.
SLEEP, Vol. 26, No. 8, 2003
1000
Neurocognitive Function in Sleep Apnea—Friedman et al
The magnitude of the changes in cognitive scores after adenotonsillectomy was calculated as the effect sizes and relative difference. Effect
sizes are calculated by taking the difference between the means before
and after treatment and dividing it by the standard deviation of the same
measure before treatment. Effect sizes are used to translate the beforeand-after changes in a 1-group situation into a standard unit of measurement that will provide a clearer understanding of health-status results.27
Cohen28 defined an effect size of 0.20 as small, 0.50 as moderate, and
0.80 or greater as large. The relative difference is calculated by dividing
the difference between the pretreatment and posttreatment scores by the
pretreatment score.
and polysomnographic data.15 All children were followed after adenotonsillectomy in our outpatient clinic, but PSGs were not repeated after
the operation as part of this study.
Statistical Analysis
Parametric tests were used when appropriate (for normally distributed
variables): group t-test, paired t-test, and analysis of variance.
Correlations were made using the Pearson Correlation Coefficient Test.
For nonnormally distributed variables, we used nonparametric tests:
Wilcoxon Signed Rank Test, Mann Whitney U-Test, and Spearman
Correlation Coefficient. Data analysis was performed using SPSS
(SPSS, Inc., Chicago, Ill).
RESULTS
Table 1—Sleep characteristics* of children with obstructive sleep
apnea syndrome and control subjects
Sleep characteristic
OSAS
n = 39
Control
n = 20
P value
Difficulties at bedtime
Restless sleep
Child wakes up at night
Child sits in bed during sleep
Child sleeps with his mouth open
Child sweats during sleep
Snoring
Child snores at least half of the sleep time
Breathing difficulties during sleep
Apneas observed by the parents
Difficulties waking up in the morning
Child complains of being tired when wakes up
Childs complains of being tired in the afternoon
Daytime tiredness/sleepiness
0 (0 – 4)
3 (0 – 4)
2 (0 – 4)
1 (0 – 4)
4 (0 – 4)
1 (0 – 1)
3.5 (0 –4)
3 (0 – 4)
3 (0 – 4)
2 (0 – 4)
3 (0 – 4)
2 (0 – 4)
1 (0 – 4)
1 (0 – 4)
0 (0 – 2)
1 (0 – 3)
1 (0 – 2)
0 (0 – 0)
0 (0 – 4)
0 (0 – 2)
0 (0 – 1)
0 (0 – 1)
0 (0 – 1)
0 (0 – 0)
1 (0 – 4)
1 (0 – 4)
0 (0 – 2)
0 (0 – 2)
.24
.0003
0.003
.0009
.0001
.02
.0000
.0000
.0000
.0000
.02
.004
.002
.0001
Subjects
Between September 2000 and June 2002, 41 children with OSAS
aged 5 to 9 years and 20 control children (10 boys and 10 girls, mean age
7.4 ± 1.4 years) underwent neurocognitive testing. Two children were
excluded from the OSAS group because their cognitive test results were
more than 3 SD above the mean. Thus, 39 children with OSAS (25 boys
and 14 girls; mean age, 6.8 ± 0.2 years) comprised the study group
(Figure 1). Twenty-seven of the 39 children with OSAS had a follow-up
neurocognitive evaluation, including questionnaires and cognitive testing, 6 to 10 months after adenotonsillectomy. Twelve children were not
reevaluated; 9 of the 39 children with OSAS did not undergo adenotonsillectomy (5 according to the otolaryngologist’s decision, 4 due to
parental decisions), and 3 others did not return for the follow-up neurocognitive evaluation. Fourteen of the 20 children in the control group
were also reevaluated using the same cognitive tests 6 to 10 months after
the first evaluation (time controls).
There were no significant differences between the 27 children who
comprised the study group and the 12 who did not repeat the neurocognitive evaluation, with regard to their history according to the questionnaires, the baseline polysomnographic data, and the neurocognitive tests
obtained at baseline.
There were no significant differences between the OSAS group (n =
39) and the control group (n = 20) in socioeconomic or health status,
except for a higher prevalence of allergic rhinitis, asthma, and a tendency to use symptom-relieving medication in the OSAS group. There were
no significant differences between the groups in number of hospitalizations, family history of snoring, and parents who smoked.
Of the 39 children with OSAS, 26 had undergone PSG as part of the
initial evaluation. Their mean RDI was 6.5 ± 4.3 (range: 1.0-20.3); their
mean arousal index was 19 ± 6 (range: 11.9-25.2), and their mean desaturation index was 0.6 ± 0.7 (range: 0-2.7). The 9 children who did not
undergo adenotonsillectomy had a lower RDI (4.3 ± 2.6; range: 1.5-7.6)
as compared with the 17 other children who did undergo adenotonsillectomy (7.5 ± 5, range: 1-20.3).
*Data are presented as the median (range) of occurrence on a 5-point scale (0, never ; 1,
seldom; 2, sometimes; 3, often; 4, almost every night), obtained by sleep questionnaires
before treatment. (Mann-Whitney U test). OSAS refers to obstructive sleep apnea syndrome.
Table 2—Neurocognitive functions* before treatment in children with
obstructive sleep apnea syndrome and in healthy controls.
Cognitive test
OSAS
n = 39
Control
n = 20
P value
Vocabulary
Gestalt closure
Number recall
Triangles
Word order
Matrix analogies
Spatial memory
Sequential Processing Scale
Simultaneous± Processing Scale
Mental Processing Composite
10.4 ± 2.9
11.4 ± 2.6
11.4 ± 2.6
9.3 ± 2.9
10.1 ± 2.7
9.7 ± 3.4
10.4 ± 2.5
104.6 ± 14.4
101.7 ± 12.6
102.9 ± 12.9
10.6 ± 2.3
11.0 ± 2.9
12.0 ± 3.1
10.2 ± 2.3
11.5 ± 1.7
11.5 ± 2.4
11.3 ± 2.1
111.9 ± 15.4
106.9 ± 9.3
109.9 ± 9.4
.70
.76
.80
.70
.02
.02
.60
.08
.09
.02
*Data are presented as mean ± SD. OSAS refers to obstructive sleep apnea syndrome.
Table 3—Neurocognitive function* in children with obstructive sleep apnea syndrome who
underwent adenotonsillectomy and controls
Cognitive test
Vocabulary
Gestalt closure
Number recall
Triangles
Word order
Matrix analogies
Spatial memory
Sequential Processing Scale
Simultaneous Processing Scale
Mental Processing Composite
OSAS
(n = 27)
Before
After
10.3 ± 2.7
11.5 ± 2.0
11.2 ± 2.7
9.2 ±3.0
9.8 ± 2.9
9.8 ± 3.1
10.4 ± 2.6
102.8 ± 15.6
101.4 ± 12.1
102.1 ± 13.6
10.8 ± 2.6
13.1 ± 1.9
11.2 ± 2.8
10.9 ± 3.2
11.6 ± 3.1
11.4 ± 2.1
11.7 ±2.6
109.3 ± 19
113.8 ± 14
113.2 ± 14
P value
Control
(n = 14)
First
Second
P value
.147
.001
.90
.02
.001
.012
.046
.03
.001
.001
10.9 ± 2.4
11.4 ± 2.6
12.1 ± 2.9
10.3 ± 3.9
11.7 ± 1.7
11.1 ± 1.9
11.8 ±1.8
112.8 ± 14.9
108.3 ±10.2
113.3 ± 9.7
11.3 ± 1.3
11.6 ± 2.3
12.3 ± 2.7
11.0 ± 2.7
11.6 ± 2.1
12.6 ±1.9
11.9 ±1.3
112.9 ±15.5
113.0 ± 10.6
115.6 ± 10.4
.38
.61
.69
.28
.90
.26
.80
.98
.025
.035
Data are presented as mean ± SD before and after adenotonsillectomy in the OSAS (obstructive sleep apnea syndrome)
group and for baseline and repeated testing in the control group.
SLEEP, Vol. 26, No. 8, 2003
1001
Sleep Questionnaire
As seen in Table 1, the children with OSAS had
significantly higher scores on the sleep questionnaire, as compared to healthy controls, in bedtime
difficulties, restless and fragmented sleep, tendency
to breathe with open mouth, and tendency to sweat
during sleep. Snoring, breathing difficulties, and
episodes of apnea were significantly more prevalent in the OSAS group, as were difficulties in waking up and reports of daytime sleepiness.
Parents reported that children with OSAS had
significantly more attention and concentration difficulties, restlessness, and a tendency to act impulsively and carelessly.
Comparison of the responses to the questionnaires before and 6 to 10 months after adenotonsilNeurocognitive Function in Sleep Apnea—Friedman et al
lectomy revealed significant improvement in sleep characteristics, as
reflected in questions concerning restless sleep (the score decreased
from a median of 3 [range: 0-4] to 1 [range: 0-1], P < .01); breathing difficulties (from 3 [range: 0-4] to 1 [range: 0-4], P < .001); snoring (from
3.5 [range: 1-4) to 1 [range: 0-4], P < .001); and apneas during sleep
(from 2 [range: 0-4] to 0 [range: 0-2], p < .005). There were no significant changes in reports of bedtime and wake-up problems and of daytime sleepiness. Improvement in the child’s behavior during the day was
shown in reports of restlessness (0.08) and tendency to be easily distracted (0.07).
subtests Triangles, and Matrix Analogies (effect size of 0.24 and 0.44,
respectively). In the remaining subtests, the change over time in the control group was not significant (Table 4). The scores of the general scales
improved significantly in the OSAS group, with large effect size for the
Simultaneous Processing Scale (1.0) and Mental Processing Composite
(0.86), and moderate effect size for the Sequential Processing Scale
(0.44). Two of the general K-ABC scales also improved significantly in
the control group, but the changes were smaller (effect size 0.38 and 0.33
for Simultaneous Mental Processing and Mental Processing Composite,
respectively). The relative difference of the changes for these 2 general
scales was significantly higher in the OSAS group as compared with the
normal controls (P < .01).
Neurocognitive Assessment
Children with OSAS showed impaired neurocognitive performance compared with
healthy children (Table 2). As compared with
those of controls, the scores of children with
OSAS were significantly lower in the K-ABC
in the subtests Word Order (P < .02) and Matrix
Analogies (P < .02) and in the general scale of
Mental Processing Composite (P < .02). The
trend of poorer neurocognitive performance
was shown in most of the other K-ABC subtests
(Table 2). There was no significant difference
between the groups in the Vocabulary test of the
WISC-R95.
There was no correlation between neurocognitive performance and OSAS severity (represented by RDI or SaO2) or indexes of sleep
fragmentation (number of arousals and awakenings) (Spearman correlation coefficient).
Effect of Adenotonsillectomy
Six to 10 months after adenotonsillectomy,
children with OSAS demonstrated significant
improvement in neurocognitive performance
(Table 3). The mean scores improved significantly in the OSAS group in the subtests
Gestalt Closure (P < .001), Triangles (P < .02),
Word Order (P < .001) and Matrix Analogies (P
< .02). None of these subtests changed significantly in the control group. All 3 K-ABC general scales showed significant improvement
after adenotonsillectomy (Table 3): Sequential
Processing Scale (102.8 ± 15.6 to 109.3 ± 19, P
< .03), Simultaneous Processing Scale (101.4 ±
12.1 to 113.8 ± 14, P < .001), and the Mental
Processing Composite, a score that sums up all
the K-ABC subtests, (102.1 ± 13.6 to 113.2 ±
14, P < .001). Figure 2 shows the individual
change between scores of the K-ABC scales
before and after adenotonsillectomy in 27 children with OSAS and 14 controls.
In order to compare the magnitude of the
change in neurocognitive functions after adenotonsillectomy in the OSAS group, and in the
second evaluation in the control group, we calculated the effect size and relative difference of
the neurocognitive tests (Table 4).
Improvement expressed as effect size of 0.2
was documented in the OSAS group in all but 1
of the K-ABC subtests. In 3 of the subtests
(Gestalt Closure, Triangles and Word Order),
the effect size was > 0.50, indicating moderate
and more-meaningful change. The changes in
scores in the control group were small in the
SLEEP, Vol. 26, No. 8, 2003
Figure 2—Individual data of the 3 Kaufman Assessment Battery for Children general scales in the obstructive sleep apnea
syndrome (OSAS) group (n = 27) (before [pre] and after [post] adenotonsillectomy), and the control group (n = 14) (first [1st]
at baseline, second [2nd] 6-10 months later). Mean ± SD scores are given for each group. 2a: data for Sequential Processing
Scale; 2b: data for Simultaneous Processing Scale; 2c: data for Mental Processing Scale. *P < .001; **P < .03
1002
Neurocognitive Function in Sleep Apnea—Friedman et al
DISCUSSION
mation efficiently, thereby lowering their learning abilities and academic performance. Our findings cannot rule out the possibility of partial
The results of the present study confirm previous reports indicating
irreversible damage to academic function even after treatment.8 The
impaired neurocognitive functions in children with OSAS. The results
impaired neurocognitive function found here can cause a cumulative
also show that treatment with adenotonsillectomy significantly improves
deficit in academic achievements that may be detected only later in life.
most neurocognitive functions, at least in mild to moderate OSAS, when
It can also cause an academic gap between the child and his or her classmeasured several months following therapy. The magnitude of the
mates that requires time and effort to reduce.
improvement was significantly higher in children with OSAS as comThere was no significant difference between the 2 groups in the
pared with normal children who were followed as a control group. The
Vocabulary test. Findings in adults with OSAS are variable. Some studfinding that the mean scores of the cognitive tests of the OSAS group
ies reported lower function in this task as a result of sleep apnea,34 while
after adenotonsillectomy did not differ from the healthy controls indiothers did not.29 Vocabulary reflects the child’s experiences and educacates that the impairment in neurocognitive functions was mostly
tion environment and is alleged to be insensitive to neurologic changes
reversible, at least by 6 to 10 months following adenotonsillectomy. The
in the brain.18 Functioning in this test reflects the continuous impact of
children with OSAS were otherwise healthy children who had hypertrothe environment. The process of learning and accumulating information
phied adenoids and tonsils with mild to moderate OSAS. Several months
starts in infancy and is prolonged.21 This may explain why the test is
after their children’s adenotonsillectomy, parents reported significant
resistant to possible neurologic impairment.
improvements in their children’s sleep characteristics, as well as a tenIntermittent hypoxemia and disruption of sleep architecture are the
dency to improve behavior parameters, such as restlessness (P = .08) and
main physiologic features of OSAS. Their relative contribution to the
the ability to maintain attention (P = .07).
neurocognitive deficits is still unclear. Several studies in adults found a
correlation between blood-gas measurements and neurocognitive perforNeurocognitive Functions
mance.29,31,33 The degree of nocturnal hypoxemia showed a positive correlation with the severity of neurocognitive impairment in tests measurThis study evaluated specific neurocognitive functions. The chosen
ing attention, problem solving, and short-term recall.29 Deficits of neutest battery enabled examination of the cognitive-processing style
rocognitive executive functions related to the prefrontal area in the coramong children suffering from OSAS. Performance in the K-ABC test
tex failed to improve significantly after treatment, suggesting irrereflects the ability of a child to obtain academic achievements.20
versible anoxic disruption.30,31,35 Sleep disruption without hypoxemia
When choosing the tests, we had in mind that, in adults, the most fremay also cause impairment in cognitive functioning.32,36 It is likely that
quently reported impaired neurocognitive functions in patients with
both hypoxemia and sleep fragmentation act synergistically in introducOSAS were verbal and visual short-term memory, attention capacity,
ing neurocognitive dysfunction. Recently, Beebe and Gozal37 presented
29-32
problem-solving strategies, and general intelligence.
Adults with
a theoretic model suggesting that restorative processes that occur during
OSAS display performance difficulties in assignments that require attensleep, as well as functional homeostasis of the cortex, may be disrupted
tion or immediate and delayed recall of verbal and visual informaas a consequence of both hypoxemia and sleep fragmentation. In the pre29,33
tion.
Other findings include impairments in high cognitive functions
sent study, we did not find any correlation between measures of oxygen
such as problem solving, executive functions, and sequential thinking
saturation (mean nocturnal SaO2, nadir SaO2, desaturation index), sleep
and deficits in learning abilities.29,30,33,34
disruption (number of arousals and awakenings per hour), or OSAS
Gozal7 has noted a link between sleep-disordered breathing and poor
severity (represented by RDI) and the neurocognitive scores. Most chilacademic achievement, reporting a high prevalence of OSAS among
dren in the present study had mild to moderate OSAS without evidence
first-graders in the lowest tenth percentile of their class, and an improveof significant hypoxemia during sleep.
ment in their school performance after adenotonsillectomy. Our study
The relatively small number in the control group presents a limitation
confirms that children with OSAS are at risk to be underachievers. We
of
the study. It was difficult to recruit healthy children from the same
found significant differences between children with OSAS and a control
school and socioeconomic status; however, we believe the statistical difgroup in cognitive tests that have been shown to correlate with academferences we found are still valid. In addition, the relatively small numic functioning at school. Children with OSAS showed significantly poorber (n = 26) of children with PSG data and the variety of neurocognitive
er performance in the Matrix Analogies test. This particular test has been
variables limited the analysis, and a larger-scale study may be needed in
shown to correlate highly with school grades20,21 and requires analytic
order to evaluate the relationship between the different sleep characterthinking, an essential factor in academic functioning. This subtest
istics and neurocognitive impairments. The fact that PSG was not repeatrequires functions such as auditory-visual integration and auditoryed after adenotonsillectomy may represent another relative limitation of
motor memory. Poor performance in this test indicates a short attention
this study; however, we have focused on neurocognitive function. A
span.19,20 The fact that children with OSAS show a lower function in the
repeat PSG could be useful to identify the sleep characteristics that are
Mental Processing Composite suggests that they do not process inforrelevant to the improvement or nonimprovement in neurocognitive function. However, the fact that adenotonsilTable 4—Effect size and relative difference of neurocognitive change from baseline lectomy improves breathing during sleep and cures OSAS
in controls and before and after adenotonsillectomy in children with obstructive sleep in more than 80% of children is well documented.15-17
apnea syndrome
Cognitive Test
Vocabulary
Gestalt closure
Number recall
Triangles
Word order
Matrix analogies
Spatial memory
Sequential Processing Scale
Simultaneous Processing Scale
Mental Processing Composite
Controls
Relative difference
OSAS
Controls
P value
0.19
0.62
0.015
0.59
0.68
0.46
0.48
0.44
1.00
0.86
0.15
0.08
0.056
0.24
-0.02
0.44
0.05
0.005
0.38
0.33
0.072
0.155
0.038
0.294
0.250
0.28
0.20
0.07
0.129
0.112
.95
.03
.81
.25
.013
.34
.15
.10
.01
.01
0.075
0.032
0.023
0.117
0.010
0.166
0.036
0.004
0.046
0.04
OSAS refers to obstructive sleep apnea syndrome.
SLEEP, Vol. 26, No. 8, 2003
The Effect of Adenotonsillectomy
Effect size
OSAS
1003
Previous reports have shown an improvement in symptoms and nocturnal hypoxemia,15,16 improved right ventricular function,3 improved respiratory disturbance as measured by PSG,17 improvement in growth factors,2 and
improvement in behavior and quality of life19 following
adenotonsillectomy. Little is known about specific neurocognitive function following adenotonsillectomy. Gozal
and Pope8 suggested that the learning problems might be
only partially reversible. In the present study, neurocognitive function significantly improved following adenotonNeurocognitive Function in Sleep Apnea—Friedman et al
sillectomy. As seen in Table 4, the effect size of the change in neurocognitive function indicates moderate and large improvement in most
tests.28 The general score of the Mental Processing Composite showed a
significantly large improvement after adenotonsillectomy (effect size of
0.86). An improvement of 11 points of IQ in the Mental Processing
Composite following adenotonsillectomy is a very substantial change.
This change enables the children to reach their original abilities and fulfill their cognitive potential. The relative difference in scores was significantly higher in children with OSAS as compared with the controls
(Table 4). These findings demonstrate a significant improvement in the
ability to process stimuli in sequential and simultaneous manners.
Cognitive factors such as perceptual closure, inference, and organization
improved significantly after adenotonsillectomy. In addition, visual and
auditory short-term memory, as well as the ability to solve problems and
to think analytically improved. These findings suggest that OSAS is a
reversible disruptive factor to the neurocognitive function of children, at
least in the short term (6 to 9 months after therapy). Theoretically, adenotonsillectomy could have affected neurocognitive performance secondary to improved hearing, not necessarily improved sleep characteristics.
Additional longer-term studies, starting in children at a younger age,
are needed in order to explore the mechanism of the neurocognitive dysfunction in children with OSAS, its relationship with OSAS severity,
and the long-term consequences of sleep-disordered breathing in
younger-age children.
In summary, the present study confirms an impaired neurocognitive
function in otherwise healthy children with mild to moderate OSAS due
to hypertrophied adenoids and tonsils. Six to 10 months following adenotonsillectomy, most impaired functions improved to the level of the
control group, indicating that the impaired neurocognitive functions are
fully reversible.
19. Goldstein NA, Fatima M, Campbell TF, Rosenfeld RM. Child behavior and quality of
life before and after tonsillectomy and adenoidectomy. Arch Otolaryngol Head Neck
Surg 2002;128:770-5.
20. Kaufman SA, Kaufman NL. Kaufman Assessment Battery for Children-Israeli Version.
Interpretive Manual. Jerusalem: Ministry of Education, Culture & Sports; 1996.
21. Kahan S. Wechsler Intelligence Scale for Children-Revised 95-Manual. Jerusalem:
Ministry of Education, Culture and Sport; 1998.
22. Kaufmn SA. Intelligence Testing with the WISC-R. New York: Wiley Interscience;
1979.
23. Rechtschaffen A, Kales A. A manual of standardized terminology: techniques and scoring system for sleep stage of human subjects. US Public Health Service, 1968. NIH
Publication No. 204.
24. EEG arousals: scoring rules and examples: a preliminary report from the Sleep Disorders
Atlas Task Force of the American Sleep Disorders Association. Sleep 1992;15:173-84.
25. Mograss MA, Ducharme FM, Brouillette RT. Movements/arousals. description, classification, and relationship to sleep apnea in children. Am J Respir Crit Care Med
1994;15:1690-6.
26. Standards and indications for cardiopulmonary sleep studies in children. American
Thoracic Society. Am J Respir Crit Care Med 1996;153:866-78.
27. Kazis LE, Anderson JJ, Meenan RF. Effect sizes for interpreting changes in health status. Med Care 1989;27(3Suppl):S178-89.
28. Cohen J. Statistical power analysis for the behavioral sciences. New York: Academic
Press; 1977:8.
29. Findley L, Barth JT, Powers DC, Wilhoit SC, Boyed DG, Scratt PM. Cognitive impairment in patients with obstructive sleep apnea and associated hypoxemia. Chest
1986;90:686-90.
30. Naegele B, Pepin JL, Levy P, Bonnet C, Pellat J, Feuerstein C. Cognitive executive dysfunction in patients with obstructive sleep apnea syndrome after CPAP treatment. Sleep
1998;21:392-7.
31. Bedard MA, Montplaisir J, Malo J, Richer F, Rouleau I. Persistent neuropsychological
deficits and vigilance impairment in sleep apnea syndrome after treatment with continuous positive airway pressure (CPAP). J Clin Exp Neuropsychol 1993;15:330-41.
32. Englman HM, Kingshott RN, Martin SE, Douglas NJ. Cognitive function in the sleep
apnea/hypopnea syndrome (SAHS). Sleep 2000;23(Suppl 4):S102-8.
33. Naegele B, Thouvad V, Pepin JL, et al. Deficits of cognitive executive functions in
patients with sleep apnea syndrome. Sleep 1995;18:43-52.
34. Rhodes SK, Shimoda KC, Waid LR, et al. Neurocognitive deficits in morbidly obese
children with obstructive sleep apnea. J Pediatr 1995;127:741-4.
35. Feuerstein C, Naegele B, Pepin JL, Levy P, Frontal lobe-related cognitive functions in
patients with sleep apnea syndrome before and after treatment. Acta Neurol Belg
1997;97(2):96-107.
36. Martin SE, Engelman HM, Dery IJ, Douglas NJ. The effect of sleep fragmentation on
daytime function. Am J Respir Crit Care Med 1996;153:1328-32.
37. Beebe DW, Gozal D. Obstructive sleep apnea and the prefrontal cortex: towards a comprehensive model linking nocturnal upper airway obstruction to daytime cognitive and
behavioral deficits. J Sleep Res 2002;11:1-16.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
Ali NJ, Pitson DJ, Stradling JR, Snoring, sleep disturbance, and behavior in 4-5 year
olds. Arch Dis Child 1993;68:360-6.
Bar A, Tarasiuk A, Segev Y, Phillip M, Tal A. The effect of adenotonsillectomy on serum
insulin-like growth factor-I and growth in children with obstructive sleep apnea syndrome. J Pediatr 1999;135:76-80.
Tal A, Leiberman A, Margulis G, Sofer S. Ventricular dysfunction in children with
obstructive sleep apnea: radionucleide assessment. Pediatr Pulmonol 1988;4:139-43.
Amin RS, Kimball TR, Bean JA, et al. Left ventricular hypertrophy and abnormal ventricular geometry in children and adolescents with obstructive sleep apnea. Am J Respir
Crit Care Med 2002;165:1395-9.
Guilleminault C, Korobkin R, Winkle R. A review of 50 children with obstructive sleep
apnea syndrome. Lung 1981;159:275-87.
Chervin RD, Dillon JE, Bassetti C, Ganoczy DA, Pituch KJ. Symptoms of sleep disorders, inattention, and hyperactivity in children. Sleep 1997;20:1185-92.
Gozal D. Sleep-disordered breathing and school performance in children. Pediatrics
1998;102:616-20.
Gozal D, Pope DW Jr. Snoring during early childhood and academic performance at
ages thirteen to fourteen years. Pediatrics 2001;107:1394-9.
Owens J, Opipari L, Nobile C, Spirito A. Sleep and daytime behavior in children with
obstructive sleep apnea and behavioral sleep disorders. Pediatrics 1998;102:1178-84.
Rosen CL. Clinical features of obstructive sleep apnea hypoventilation syndrome in otherwise healthy children. Pediatr Pulmonol 1999;27:403-9.
Bulden S, Lushington K, Kennedy D, Martin J, Dawson D. Behavior and neurocognitive performance in children aged 5-10 years who snored compared to controls. J Clin
Exp Neuropsychol 2000;22:494-8.
Ali NJ, Pitson D, Stradling JR. Sleep disordered breathing: effects of adenotonsillectomy on behavior and psychological functioning. Eur J Pediatr 1996;155:56-62.
Goldstein NA, Post JC, Rosenfeld RM, Campbell TF. Impact of tonsillectomy and adenoidectomy on child behavior. Arch Otolaryngol Head Neck Surg 2000;126:494-8.
Harvey JM, O’Callaghan MJ, Wales PD, Harris MA, Masters IB. Six month follow-up
of children with obstructive sleep apnea. J Pediatr Child Health 1999;35:136-9.
Tal A, Bar A, Leiberman A, Tarasiuk A. Changes in sleep characteristics following adenotonsillectomy in children with obstructive sleep apnea syndrome. Chest
2003;124:948-53.
Stradling JR, Thomas G, Warely ARH, Williams P, Freeland A. Effect of adenotonsillectomy on nocturnal hypoxemia, sleep disturbance, and symptoms in snoring children.
Lancet 1990;335:249-53.
Suen JS, Arnold JE, Brooks LJ. Adenotonsillectomy for treatment of obstructive sleep
apnea in children. Arch Otolaryngol Head Neck Surg 1995;121:525-30.
Miller E. Some basic principals of neuropsychological assessment. In:Crawford RJ,
Parker DM. McKinnley WW, eds. A Handbook of Neuropsychological Assessment.
Hillsdale: Lawrence Erlbaum Associates Ltd; 1992:15-9.
SLEEP, Vol. 26, No. 8, 2003
APPENDIX
The Sleep Questionnaire
Child’s demographic information
Name & ID
Address
Telephone number
Date of birth
Gender
Number of siblings
Number of persons sharing the child’s room
Parent’s demographic information
Father’s Profession
Father’s Ethnicity
Mother’s Profession
Mother’s Ethnicity
Family (first degree members) information
Smoking (Yes/No)
Snoring (Yes/No)
Asthma or chronic lung disease (Yes/No)
Child’s Medical Problems
Medications
Allergies
Adenoids and/or tonsils removed (Yes/No)
Asthma (Yes/No)
Frequent colds (Yes/No)
1004
Neurocognitive Function in Sleep Apnea—Friedman et al
Constant runny nose (Yes/No)
Cardiac disease (Yes/No)
Arthritis (Yes/No)
Does your child have a diagnosed behavioral problem (Yes/No)
The following questions can be answered by “never”, “seldom”, “sometimes” “often” or “almost always” (score of 0,1,2,3,4, respectively).
Does your child go to bed unwillingly?
Does your child express fear or worries before going to bed?
Does your child complain about difficulties going to sleep?
Does your child complain of difficulties falling asleep at night?
Does it take more than 30 minutes for your child to fall asleep at night?
Is your child a restless sleeper?
Does your child wake up at night?
Does your child get up to go to the bathroom during the night?
While asleep, does your child ever sit up in bed?
Is your child a mouth-breather during sleep?
Is your child a daytime mouth-breather?
Does your child have nightmares?
Does your child have problems with bed wetting?
Does your child sweat more than usual during sleep?
Have you observed him/her sleepwalking?
Does your child snore during sleep?
Does he snore during at least half of the night?
Does your child have difficulties breathing during sleep?
Do you ever shake your child to make him/her breathe again when
asleep?
Does your child stop breathing during sleep?
Is your child easy to wake up in the morning?
Is your child sleepy when he/she wakes up in the morning?
Is your child sleepy during the daytime?
Does your child complain about tiredness/sleepiness in the afternoon?
How long does your child sleep at night?
At what time does your child go to bed?
How long does your child sleep during the day?
When answering the next six questions, please use “not at all”, “sometimes” or “very much.”
Does the behavior described in each sentence characterize your child? :
He/she has difficulties concentrating during school activities.
He/she has difficulties in maintaining attention on one task for a long
time.
He/she has a tendency to act carelessly and not notice details.
He/she is easily distracted from his/her activities (by noise, etc.).
He/she is restless, jumpy.
Many times he/she acts impulsively.
SLEEP, Vol. 26, No. 8, 2003
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Neurocognitive Function in Sleep Apnea—Friedman et al