Daytime sleepiness, cognitive performance and mood after continuous positive airway pressure for the sleep apnoea/hypopnoea syndrome

Abstract

Patients with the sleep apnoea/hypopnoea syndrome often receive continuous positive airway pressure to improve their symptoms and daytime performance, yet objective evidence of the effect of this treatment on cognitive performance is lacking.
A prospective parallel group study was performed comparing the change in objective daytime sleepiness as assessed by multiple sleep latency, cognitive function, and mood in 21 patients (mean (SE) number of apnoeas and hypopnoeas/hour 57 (6)) who received continuous positive airway pressure for three months and 16 patients (49(6) apnoeas and hypopnoeas/hour) who received conservative treatment for a similar period.
Both groups showed significant within group changes in cognitive function between baseline and three months, but when comparisons were made between groups the only significant difference was a greater improvement in multiple sleep latency with continuous positive airway pressure. However, the improvement in sleep latency with continuous positive airway pressure was relatively small (3.5 (0.5) to 5.6 (0.7) min). The group treated with continuous positive airway pressure was divided into those who complied well with treatment (> 4.5 hours/night) and those who did not. Those who complied well (n = 14) showed significant improvement in mean sleep latency and also in depression score compared with the controls but no greater improvement in cognitive function.
This study confirms significant improvements in objective sleepiness and mood with continuous positive airway pressure, but shows no evidence of major improvements in cognitive function.

Full text

T7horax
1993;48:91
1-914
Daytime
sleepiness,
cognitive
performance
and
mood
after
continuous
positive
airway
pressure
for
the
sleep
apnoea/hypopnoea
syndrome
Heather
M
Engleman,
Katherine
E
Cheshire,
Ian
J
Deary,
Neil
J
Douglas
Abstract
Background-Patients
with
the
sleep
apnoea/hypopnoea
syndrome
often
receive
continuous
positive
airway
pres-
sure
to
improve
their
symptoms
and
daytime
performance,
yet
objective
evi-
dence
of
the
effect
of
this
treatment
on
cognitive
performance
is
lacking.
Methods-A
prospective
parallel
group
study
was
performed
comparing
the
change
in
objective
daytime
sleepiness
as
assessed
by
multiple
sleep
latency,
cogni-
tive
function,
and
mood
in
21
patients
(mean
(SE)
number
of
apnoeas
and
hypopnoeas/hour
57
(6))
who
received
continuous
positive
airway
pressure
for
three
months
and
16
patients
(49(6)
apnoeas
and
hypopnoeas/hour)
who
received
conservative
treatment
for
a
similar
period.
Results-Both
groups
showed
significant
within
group
changes
in
cognitive
func-
tion
between
baseline
and
three
months,
but
when
comparisons
were
made
between
groups
the
only
significant
dif-
ference
was
a
greater
improvement
in
multiple
sleep
latency
with
continuous
positive
airway
pressure.
However,
the
improvement
in
sleep
latency
with
con-
tinuous
positive
airway
pressure
was
rel-
atively
small
(3.5
(0.5)
to
5
6
(0.7)
min).
The
group
treated
with
continuous
posi-
tive
airway
pressure
was
divided
into
those
who
complied
well
with
treatment
(>4-5
hours/night)
and
those
who
did
not.
Those
who
complied
well
(n
=
14)
showed
significant
improvement
in
mean
sleep
latency
and
also
in
depression
score
compared
with
the
controls
but
no
greater
improvement
in
cognitive
func-
tion.
Conclusion-This
study
confirms
signifi-
cant
improvements
in
objective
sleepi-
ness
and
mood
with
continuous
positive
airway
pressure,
but
shows
no
evidence
of
major
improvements
in
cognitive
finction.
(Thorax
1993;48:911-914)
Daytime
sleepiness,
impaired
daytime
perfor-
mance
and
lowered
mood
are
common
symptoms
of
the
sleep
apnoea/hypopnoea
syndrome,
and
there
is
objective
evidence
of
daytime
sleepiness
and
impaired
cognitive
performance
in
these
patients.'-3
Treatment
with
continuous
positive
airway
pressure
has
been
shown
to
improve
nocturnal
breathing
pattern,4
nocturnal
sleep
quality,5
objective
daytime
sleepiness,6
and
also
mood.7
Although
patients
with
the
sleep
apnoea/
hypopnoea
syndrome
frequently
report
improvements
in
subjective
daytime
function
with
continuous
positive
airway
pressure,
objective
confirmation
of
its
effect
on
cogni-
tive
function
is
lacking.
We
therefore
con-
ducted
a
controlled
trial
to
assess
changes
in
cognitive
performance,
mood
and
daytime
sleepiness
in
such
patients
after
treatment.
Methods
A
prospective
parallel
group
study
was
per-
formed
comparing
the
change
in
cognitive
function,
mood
and
objective
daytime
sleepi-
ness
after
at
least
three
months
(mean
(SE)
6
(1)
months)
of
treatment
with
either
con-
tinuous
positive
airway
pressure
or
conserva-
tive
treatment
only.
Each
patient
gave
written
informed
consent
to
the
study,
which
had
the
approval
of
the
local
ethical
advisory
commit-
tee.
All
patients
underwent
an
overnight
sleep
study
to
confirm
the
diagnosis
of
the
sleep
apnoea/hypopnoea
syndrome,
defined
as
hav-
ing
more
than
15
apnoeas
and
hypopnoeas
per
hour
of
sleep.8
Polysomnography
was
performed
using
our
standard
techniques9
with
monitoring
of
electroencephalography
(EEG),
electro-oculography
and
electromyo-
graphy,
thoracic
and
abdominal
movement
by
inductance
plethysmography,
oronasal
flow
with
a
thermocouple,
and
oxygen
satura-
tion
by
ear
oximetry
(Ohmeda
Biox
3700).
An
apnoea
was
defined
as
a
cessation
of
air-
flow
for
10
seconds
or
more,
and
a
hypo-
pnoea
as
a
reduction
in
thoracoabdominal
movement
of
50%
or
more
for
10
seconds
or
longer.8
Sleep
was
scored
by
conventional
cri-
teria'0
and
arousals
were
scored
when
there
was
a
rise
in
electromyographic
activity
dur-
ing
sleep
coincident
with
return
of
a
or
0
EEG
activity
for
at
least
1-5
seconds."
Patients
receiving
continuous
positive
airway
pressure
underwent
a
further
overnight
sleep
study
in
which
the
pressure
was
titrated
to
a
level
where
respiratory
abnormalities
and
arousals
were
minimised.
Patients
given
con-
tinuous
positive
airway
pressure
used
Sleep
Respiratory
Medicine
Unit,
Department
of
Medicine,
City
Hospital,
Edinburgh
EH10
5SB
H
E
Engleman
K
E
Cheshire
N
J
Douglas
Department
of
Psychology,
University
of
Edinburgh,
Edinburgh
EH8
9JZ
N
J
Douglas
Reprints
will
not
be
available
Received
26
February
1993
Returned
to
authors
28
May
1993
Revised
version
received
10
June
1993
Accepted
15
June
1993
911
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Engleman,
Cheshire,
Deary,
Douglas
Table
1
Mean
(SE)
clinicalfeatures
of
treatment
groups
at
baseline
assessment
CPAP
(n
=
21)
Control
(n
=
16)
p
Age
(years)
53(3)
53(3)
1
00
Body
mass
index
(kg/M2)
34(2)
32(2)
0-31
No
of
apnoeas
and
hypopnoeas/h
slept
57(6)
49(6)
0-38
No
of
arousals/h
slept
54(5)
45(6)
0-26
Minimum
oxygen
saturation
(%)
61(5)
69(4)
0-27
CPAP-continuous
positive
airway
pressure.
Easy
II
or
Sleep
Easy
III
units,
which
were
fitted
with
hidden
time
clocks.
Allocation
to
treatment
groups
was
not
randomised
but
was
partially
based
on
patients'
preference.
Half
of
the
control
group
had
declined
to
start
continuous
positive
airway
pressure
while
the
other
half
were
directly
assigned
to
conservative
treatment.
All
patients
were
given
advice
on
weight
loss
and
avoidance
of
evening
alcohol.
The
clini-
cal
features
of
the
two
groups
were
similar
(table
1).
ASSESSMENT
At
each
time
of
testing
all
patients
underwent
a
multiple
sleep
latency
test'2
and
on
a
non-
consecutive
day
a
3
hour
battery
of
psycho-
metric
tests,
including
assessment
of
cognitive
performance
and
mood,
as
detailed
in
table
2.
Both
sessions
were
performed
after
the
Table
2
Psychometnrc
battery
patient
had
slept
the
night
in
their
own
bed.
Patients
had
only
non-caffeinated
drinks
on
the
days
of
testing.
Because
patients
with
the
sleep
apnoea/
hypopnoea
syndrome
tend
to
have
arousals
associated
with
apnoeas
and
hypopnoeas
soon
after
sleep
onset,
the
definition
of
sleep
onset
used
in
the
multiple
sleep
latency
test
was
modified
to
one
20
second
epoch
of
any
sleep
stage.
This
definition
of
sleep
onset
in
such
patients
has
since
been
accepted
by
the
American
Sleep
Disorders
Association.'3
The
psychometric
battery
was
designed
to
incor-
porate
tests
of
a
wide
range
of
neuropsycho-
logical
function,
including
general
level
of
function,
visuomotor
skill,
concentration
abil-
ity,
vigilance,
memory,
and
mood.
A
stan-
dardised
alternative
to
the
word
list
in
the
auditory
verbal
learning
test
was
used
in
the
repeat
testing
session
to
obviate
learning
related
improvements
in
score.'4
The
admin-
istration
of
the
national
adult
reading
test
rendered
an
estimate
of
premorbid
perfor-
mance
IQ.
This
estimate
was
subtracted
from
the
performance
IQ
score
obtained
from
the
Wechsler
adult
intelligence
scale
performance
subtests
to
calculate
an
"IQ
decrement"
score
for
each
patient.
Overall
change
in
cognitive
function
score
for
each
individual
was
assessed
by
using
a
summed
Z
score15
of
each
patient's
performance
in
all
cognitive
tests
in
the
battery.
Tests
of
general
function
and
of
memory
WAIS
subtests-information,
arithmetic,
block
design,
digit
symbol
substitution
TrailMaking
tasks
A
and
B
Auditory
verbal
learning
test
Premorbid
level
of
function
National
adult
reading
test
Processing
time
Concentration
Mood
Inspection
time
test
Simple
unprepared
reaction
time
Paced
auditory
serial
addition
test
(presentation
rates
2
s
and
4
s)
Driving
simulator
Hospital
anxiety
and
depression
scale
WAIS-Wechsler
adult
intelligence
scale.
Ir
-
p
<
0.02
T
CPAP
Control
Mean
sleep
latency
in
patients
with
the
sleep
apnoea
syndrome
at
baseline
and
after
treatment
with
continuous
positive
airway
pressure
(CPAP)
or
after
having
been
given
advice
alone
(control).
STATISTICS
Data
from
the
multiple
sleep
latency
test
and
the
psychometric
tests
were
analysed
by
the
BMDP
package.
16
Baseline
values
between
the
two
groups
were
compared
by
Student's
unpaired
t
tests.
Non-normally
distributed
data
were
examined
using
the
Mann-Whitney
U
test.
Two
way
analysis
of
variance
was
used
to
assess
the
interaction
of
the
treatment
and
repeated
test
factors
when
examining
the
change
in
cognitive
function
from
baseline
to
the
second
assessment
in
the
two
groups.
Results
ALL
PATIENTS
Comparison
of
treatment
groups
at
baseline
There
were
no
differences
in
psychometric
function
at
baseline
in
the
two
groups.
However,
the
mean
sleep
latency
on
the
multiple
sleep
latency
test
was
longer
in
the
conservatively
treated
group
(fig;
p
=
0
0
1).
Within
group
changes
in
scores
from
first
to
second
assessment
Both
groups
showed
significant
improve-
ments
in
scores
in
a
wide
range
of
psycho-
metric
function
tests
(table
3).
There
was
also
significant
lengthening
of
sleep
latency
in
the
multiple
sleep
latency
test
on
the
group
treated
with
continuous
positive
airway
pres-
sure.
Comparison
of
change
in
scores
from
first
to
second
assessment
between
the
two
groups
There
was
no
significant
difference
between
the
two
groups
in
changes
in
any
of
the
U1)
0
c
U1)
U1)
a)
U)
3
0
912
6
r
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Effect
of
continuous
positive
ainvay
pressure
on
sleep
apnoea
Table
3
Mean
(SE)
significant
within
group
changes
*from
first
to
second
assessment
CPAP
group
Control
group
Test
Change
p
Change
p
Information
(no
correct)
1-4(0-4)
<0-01
0-9(0-4)
0-05
Digit
symbol
substitution
(no
correct)
3-6(0-9)
<0-01
IQ:
Verbal
4-0(1-8)
<0-05
Performance
5-6(2-1)
<0-05
Full
2-1(1-0)
0-05
4-6(1-4)
<0-01
TrailMaking
task
B
(s)
-27-3(2-7)
<0-01
PASAT
(no
correct):
4s
4-3(1-5)
0-01
2s
5-3(1-7)
0-01
4-7(1-6)
0-01
Driving
response
time
(s)
-6-2(2-4)
<0-05
Sleep
latency
(min):
Mean
2-1(0-8)
0-01
Minimum
1-3(0-5)
<0-05
CPAP-continuous
positive
airway
pressure;
PASAT-paced
auditory
serial
addition
test.
*All
significant
changes
were
in
the
direction
of
improvement
in
the
tests
concerned.
psychometric
function
tests
(p
>
0-2).
Mean
sleep
latency
lengthened
significantly
in
the
treated
group
compared
with
the
control
group
(p
<
0-02;
fig).
Similarly,
the
treated
group
had
a
trend
to
greater
improvement
in
the
shortest
of
the
five
sleep
latencies
during
the
multiple
sleep
latency
test
(p
>
0-05).
GOOD
COMPLIERS
The
hidden
time
clocks
in
the
continuous
positive
airway
pressure
units
allowed
an
average
nightly
usage
to
be
calculated
for
each
patient.
The
mean
(SE)
usage
for
the
group
was
5-9
(1-4)
hours
per
night.
We
divided
the
group
treated
with
continuous
positive
airway
pressure
into
those
who
com-
plied
well
with
treatment
and
used
their
units
for
more
than
4-5
hours
per
night
(n
=
14)
and
those
who
used
it
for
less
than
4-5
hours
per
night.
The
results
for
the
good
compliers
were
compared
with
those
for
the
controls.
The
good
compliers
again
showed
signifi-
cantly
greater
improvements
in
mean
sleep
latency
compared
with
the
conservatively
treated
patients
(visit
1:
3-4
(0-5)
minutes,
visit
2:
5-5
(0-4)
minutes;
p
<
0-05)
and
shortest
sleep
latency
(visit 1:
1-3
(0-3)
min-
utes,
visit
2:
2-4
(0-3)
minutes;
p
<
0-05).
The
good
compliers
also
showed
a
signifi-
cantly
greater
improvement
in
depression
score
(p
=
0-05)
but
no
significant
improve-
ments
in
any
cognitive
function
assessment
compared
with
the
control
group.
There
was
no
difference
between
the
treated
and
control
group
in
the
change
in
weight
during
the
study
period
(treated
gained
1-4
(0-6)
kg,
control
gained
1-6
(1.3)
kg).
Discussion
This
study
shows
that
treatment
with
contin-
uous
positive
airway
pressure
results
in
improvements
in
objective
sleepiness
and
may
improve
mood
in
good
compliers,
but
we
were
unable
to
show
any
improvement
in
cognitive
performance.
We
thus
confirm
the
findings
of
Lamphere
et
al
of
an
improvement
in
objective
daytime
sleepiness
with
continu-
ous
positive
airway
pressure,
although
our
changes
are
much
less
dramatic
than
those
of
Lamphere
et
al.6
In
part,
this
may
reflect
dif-
ferences
in
criteria
of
defining
sleep
onset
during
the
daytime
naps,
which
we
defined
as
a
first
20
second
epoch
of
any
sleep
stage
rather
than
the
first
minute
of
any
sleep
stage
to
detect
short
sleep
episodes
rapidly
dis-
rupted
by
apnoeic
arousals.
Our
data
showing
a
moderate
improvement
in
sleep
latency
with
continuous
positive
airway
pressure
come
midway
between
the
dramatic
improve-
ments
reported
by
Lamphere
et
al
6
and
the
lack
of
improvement
with
continuous
positive
airway
pressure
or
uvulopalatopharyngo-
plasty,
or
both,
recently
reported
by
Sangal
et
al."7
Although
our
different
criteria
for
sleep
onset
might
change
the
absolute
value
of
multiple
sleep
latency
in
comparison
with
earlier
studies,6
it
is
difficult
to
see
how
this
could
adversely
affect
our
ability
to
detect
improvement
with
continuous
positive
airway
pressure.
We
have
confirmed
the
results
of
Derderian
et
al
that
the
treatment
may
improve
mood.7
There
has
been
a
relative
paucity
of
data
on
the
effects
of
continuous
positive
airway
pressure
on
cognitive
performance.
In
a
pro-
visional
report
Bearpark
et
al
found
improve-
ments
in
scores
in
visual
memory,
verbal
fluency,
and
mental
set
flexibility
on
retesting
after
4-5
months
of
continuous
positive
air-
way
pressure,
but
their
study
had
no
control
group
to
evaluate
the
effects
of
learning
on
performance.'8
Similarly,
Charbonneau
et
al
have
reported
improved
cognitive
function
with
the
treatment
in
an
uncontrolled
study.'9
Our
finding
of
within
group
improvements
in
cognitive
performance
on
retesting
in
both
groups
shows
that
a
learning
curve
exists
for
cognitive
function
tests.
It
also
indicates
the
need
for
control
groups
in
such
studies
and
shows
that
the
conclusions
of
Bearpark
et
al
'8
and
Charbonneau
et
al
19
that
continuous
positive
airway
pressure
improves
psycho-
metric
function
cannot
be
drawn
from
their
studies.
Our
studies
are
consistent
with
the
observation
of
Walsleben
et
al,
who
found
no
improvement
in
cognitive
function
after
two
nights
of
continuous
positive
airway
pressure
treatment
in
a
small
study
(n
=
7).3
The
lack
of
demonstrable
improvement
in
cognitive
function
in
our
study
could
be
due
to
our
choice
of
psychometric
performance
tests,
to
the
wide
interindividual
variability,
to
poor
compliance
with
treatment,
or
to
the
fact
that
there
genuinely
is
no
improvement
in
cognitive
function
which
might
be
perma-
nently
impaired
in
patients
with
the
sleep
apnoea/hypnoea
syndrome.
We
chose
the
psychometric
function
tests
to
reflect
the
abnormalities
that
we
have
previously
detected
in
patients
with
the
syndrome"
and
to
cover
a
wide
range
of
cognitive
functions.
Our
patients
were
well
within
the
operating
range
for
all
the
cognitive
function
tests
and
thus
the
lack
of
an
improvement
was
not
due
to
there
being
no
room
for
improvement
in
their
results.
We
believe
that
the
battery
of
913
on August 27, 2023 by guest. Protected by copyright.http://thorax.bmj.com/Thorax: first published as 10.1136/thx.48.9.911 on 1 September 1993. Downloaded from

Engleman,
Cheshire,
Deary,
Douglas
tests
used
is
fairly
comprehensive.
Never-
theless,
Findley
et
al
have
shown
improve-
ment
in
a
long
and
repetitive
task
designed
to
simulate
driving,20
although
it
remains
to
be
seen
whether
this
reflects
improved
cognitive
function,
a
decrease
in
daytime
microsleeps,
or
improved
performance
with
greater
famil-
iarity
with
the
task.
We
believe
that
the
large
interindividual
variability
in
cognitive
func-
tion
may
have
resulted
in
our
failure
to
find
differences
in
a
parallel
group
design
such
as
we
used.
We
are
thus
initiating
a
crossover
study
of
the
effect
of
continuous
positive
air-
way
pressure
or
placebo
on
objective
daytime
sleepiness,
cognitive
function
and
mood.
Compliance
with
treatment
was
somewhat
disappointing
in
our
study,
with
a
mean
use
of
continuous
positive
airway
pressure
of
5
9
hours/night.
We
suggest,
however,
that
this
probably
reflects
use
in
the
community
and
is
certainly
in
keeping
with
other
recent
studies
which
have
objectively
examined
compliance
in
patients
with
the
sleep
apnoea/hypnoea
syndrome.2122
This
study
shows
that
there
are
significant
improvements
in
both
objective
daytime
sleepiness
and
mood
with continuous
positive
airway
pressure
in
patients
with
the
sleep
apnoea/hypopnoea
syndrome,
but
we
found
no
evidence
of
major
improvements
in
cogni-
tive
function
with
such
treatment.
We
thank
Sisters
C
Hoy
and
M
Venneile
and
Ms
K
Stedul
and
H
Biernacka
for
technical
and
nursing
help
and
Mrs
E
Dolan
for
preparing
the
manuscript.
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on August 27, 2023 by guest. Protected by copyright.http://thorax.bmj.com/Thorax: first published as 10.1136/thx.48.9.911 on 1 September 1993. Downloaded from