Sleep apnea and disorders in cognitive and emotional functioning after stroke

1. Background

1.1 Sleep apnea and stroke

Sleep apnea is a common condition in patients who have experienced a stroke. It
is the most common form of sleep disordered breathing (SDB), a disorder with an
inefficient respiration during sleep, which is often neglected after stroke.
The reported prevalence of SDB following stroke varies from 44% to 72%. In a
recent review, the reported prevalence of SDB after stroke was 50-70%. In most
studies no relationship was found between SDB and stroke severity, topography
and the presumed etiology. SDB was found more often in recurrent stroke, than
first-ever stroke, and the frequency was similar after TIA and stroke. This
suggests that in many cases SDB is a preexistent condition. Several studies
have shown that is SDB predisposes to cardiovascular diseases.

The most common form of SDB is obstructive sleep apnea syndrome (OSAS, which is
characterized by repeated high airway obstructions during sleep, with
desaturations and arousals, leading to less efficient sleep, less deep and less
REM sleep. Patients often experience severe fatigue during the day. In patients
who have experienced a stroke, obstructive apneas (OSA), but also central
apneas (CSA) and Cheyne-Stokes breathing (CSB) are seen regularly, particularly
in the acute phase after stroke. CSA/CSB often improves in the subacute phase,
which suggest that breathing abnormalities are exacerbated bij stroke. However,
2 to 3 months after the acute stroke approximately 50% of patients still meet
the criteria of OSAS.

1.2 Sleep disordered breathing, definitions and diagnostics

For the definition of SDB, in particular OSAS, recommendations of the AASM
(American Academy of Sleep Medicine), published in 1999, are used worldwide. In
the Netherlands, these recommendations were published in the CBO guidelines
"Diagnostics and treatment of the obstructive sleep apnea for adults" in 2009

Screening for SDB may be warranted in all stroke patients who may potentially
accept CPAP treatment. SDB can be accurately diagnosed by respiratory
polygraphy, in which nasal airflow, respiratory movements, and capillary oxygen
saturation are monitored. Polysomnography offers additional information, but is
expensive and less commonly available. It should therefore be reserved for
unclear cases.
A polysomnography is a polygraphy with at least EEC (electroencephalografy),
electro-oculography (EOG) and EMG (registration electromyography).

1.3 Sleep disordered breathing (SDB), fatigue and complaints of cognitive and
emotional functioning

In the literature links are found between SDB and concentration disorders,
fatigue, memory disorders, depression and anxiety.
Excessive daytime sleepiness (EDS) and fatigue are associated with
neuropsychiatric (depression, anxiety) and cognitive disorders and have a
negative impact on rehabilitation and quality of life.

1.4 Stroke, fatigue and complaints in cognitive and emotional functioning

In patients who have experienced a stroke, disorders in emotional and cognitive
function are frequently seen. Hypersomnia, EDS (excessive daytime sleepiness)
and fatigue after a stroke was frequently seen in a recent study, as was
insomnia.

It is not yet entirely clear to what extent SDB is responsible for, or
contributes to the frequent reported emotional disorders and cognitive
function.

1.5 COMPAS study: objective and subjective cognitive complaints after stroke
In 2007 and 2008, M. van Rijsbergen, neuropsychologist and researcher at the
University of Tilburg, conducted a study in the context of her Master Thesis
Medical Psychology, on the relationship between subjective and objective memory
complaints in patients after a stroke in the St. Elisabeth and TweeSteden
Hospital. This study showed a consistent association between subjective memory
complaints and cognitive limitations, such as fatigue, anxiety and depression
in patients after stroke with a follow up of 6 months. 31

As part of her promotion research: The COMPAS study (COgnitive coMPlaints After
Stroke), (promoter Prof. Dr. M. Sitskoorn, co-promoters Dr. R. Mark, Dr. P.L.M.
de Kort), she will carry out a follow-up study in patients after stroke, which
started March 2010. In this study subjective complaints regarding cognitive and
emotional functioning are examined in relation to objective disorders in
cognition, emotion and psychiatric disorders.

1.6 Substudy in COMPAS: Relation between sleep disordered breathing (in
particular OSAS) and complaints of fatigue and emotional and behavioural
problems after a stroke.

Considering the frequency of sleepapnea in patients after stroke, the
association of sleepapnea with complaints of fatigue and cognitive disturbances
and the frequency of fatigue and cognitive impairment after stroke, it is
likely that there are links between sleepapnea and cognitive complaints after
stroke. A study with attention to the patients complaints has not yet been
conducted.

1.7 Conclusion and relevance

Sleep disordered breathing (SDB), in particular OSAS, is a common disease in
patients who have experienced a stroke. In addition, SDB is a risc factor for
stroke recurrence and other heart and vascular diseases. It is a well-known
fact that SDB results in fatigue and concentration disorders, disorders of the
cognitive and emotional functioning. In patients who have experienced a stroke,
disorders in emotional and cognitive function are frequently seen. It is not
yet entirely clear to what extent SDB is responsible for or contributes to the
frequent reported emotional and cognitive disorders after stroke.

Research in this area is of great social importance. 41 000 new patients suffer
from stroke each year in the Netherlands (ref NHS). The number of patients will
only rise, by ageing of the population in the future. Stroke is the main cause
of chronic disability in adulthood, is related to a lower quality of life and
is responsible for a great deal of docter*s consultation. SDB, in particular
OSAS, is seen in 50% of stroke patients in the subacute phase and is a risc
factor for stroke recurrence. Worldwide no standard screening is performed for
SDB after stroke. Many patients experience fatigue and cognitive disturbances
after stroke. Patients with SDB also experience this. It seems likely that
there*s a relationship between subjective cognitive complaints, objective
cognitive and emotional disorders and SDB in patients after stroke. This study
can provide more insight on this relationship en could be a start for better
treatment for patients after stroke.

1.8 Hypothesis

In patiënts who have experienced a stoke, there is a high prevelance of SDB (in
particular OSAS)

There is a relationship between SDB (in particular OSAS) and complaints of
fatigue and complaints of emotional and cognitive disturbances in patients who
have recently experienced a stroke.

There is a relationship between SDB (in particular OSAS) and objective
cognitive disorders in patients after stroke

Sleep disordered breathing (in particular OSAS) plays an important role in
fatigue complaints after a stroke.

In the subacute phase of a stroke (after 2-3 months) a portable (type 4)
polygraphy is a good screening instrument for sleepapnea.

Determination of SDB prevalence in patients after stroke

Determination of the relationships between SDB (in particular OSAS) and
complants of fatigue and complaints of emotional and cognitive disturbances in
patients who experienced a stroke.

Determination of the relationships between SDB (in particular OSAS) and
objective cognitive disorders in patients after stroke

To use a simple, portable type 4 polygraphy monitoring as a screeninginstrument
for SDB in the subacute phase of stroke, compared to the golden standard
polysomnography

This study is partly a substudy in the COMPAS study, in which patients are
followed up 2 years after their stroke. Current study will confine itself to
the first moment of inclusion in the COMPAS study, that is to say, three months
after the occurrence of the stroke.
During their regular visit to the outpatient clinic, these patients are asked
to answer a questionnaire on sleep, and a diagnostic ambulant polygraphy will
be carried out.
In case the polygraphy shows evidence of SDB, patients will be referred to a
neurologist with specialisation in sleepdisorders and a polysomnography (PSG)
will be ordered. If a patient is found to have OSAS, regular treatment will be
facilitated. Performing PSG and treatment are beyond the scope of this
research.
Current research can therefore be seen as a correlation study, in which the
correlation between SDB and cognitive and emotional disorders are measured in
patients who have experienced a recent stroke.

In addition, all patients who have experienced a stroke (including those who
won't participate in the COMPAS study) will be given a one-night type 4
portable polygraphy monitoring during their admission on the stroke care unit.
Patients who don't participate in the COMPAS study will also be asked to fill
in a questionnaire on sleep during their oupatient clinic visit, and will be
asked to participate in current study to perform an ambulant polygraphy
monitoring.
This way prevalence of SDB during acute and subacute phases of stroke can be
measured, and polygraphy type 4 monitoring can be compared to golden standard
polysomnography.

During the admission on the stroke care unit patients will be asked to answer a
10-point questionnaire and a 1-night registration with the Apneulink polygraphy
(type 4 polygraphy monitoring) is registred. During their planed, regular visit
at the outpatient clinic, 6 weeks after discharge, patients will be asked to
participate in current study. A second questionnaire on sleep will be given to
the patients to be answered at home. A second registration with the type 4
portable ambulant polygraphy will be performed. Patients can apply the monitor
easily themselves at home. After a one-night registration they can return the
device to the hospital. If, on basis of the questionnaire and/or the polygraphy
monitoring, there is a reasonable suspicion on SDB, patients will be referred
to a neurologist with experience in sleepmedicine. Polysomnography and
treatment will be performed following regular diagnostic en treatment
guidelines and is beyond the scope of this study.

Participation in this study is non-invasive, save and without specific risks.
In case the results of the questionnaire and/or the polygraphy give resons for
concerns, patients are referred to their treating physician (after consent).
Furthermore, all patients who are suspected of SDB on basis of the polygraphy
measurement are referred to a neurogist with experience in sleepmedicine for
further diagnostic procedures and possible treatment.