The role of sleep on cognition and functional connectivity in patients with multiple sclerosis
The role of sleep on cognition and functional connectivity in patients with multiple sclerosis
Quinten van Geest 0
H. E. Hulst 0
B. Westerik 0
Y. D. van der Werf 0
J. J. G. Geurts 0
0 Department of Anatomy and Neurosciences, VU University Medical Center , Amsterdam Neuroscience , VUmc MS Center Amsterdam , De Boelelaan 1108, room 13 W01, 1081 HZ Amsterdam , The Netherlands
Sleep disturbances are common in multiple sclerosis (MS), but its impact on cognition and functional connectivity (FC) of the hippocampus and thalamus is unknown. Therefore, we investigated the relationship between sleep disturbances, cognitive functioning and resting-state (RS) FC of the hippocampus and thalamus in MS. 71 MS patients and 40 healthy controls underwent neuropsychological testing and filled out self-report questionnaires (anxiety, depression, fatigue, and subjective cognitive problems). Sleep disturbances were assed with the five-item version of the Athens Insomnia Scale. Hippocampal and thalamic volume and RS FC of these regions were determined. Twenty-three patients were categorized as sleep disturbed and 48 as normal sleeping. No differences were found between disturbed and normal sleeping patients concerning cognition and structural MRI. Sleep disturbed patients reported more subjective cognitive problems, and displayed decreased FC between the thalamus and middle and superior frontal gyrus, inferior frontal operculum, anterior cingulate cortex, inferior parietal gyrus, precuneus, and angular gyrus compared to normal sleeping patients. We conclude that sleep disturbances in MS are not (directly) related to objective cognitive
Multiple sclerosis; Cognition; Sleep; Functional connectivity; fMRI
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functioning, but rather to subjective cognitive problems. In
addition, sleep disturbances in MS seem to coincide with a
specific pattern of decreased thalamic FC.
Up to 65 % of multiple sclerosis (MS) patients suffer from
cognitive problems [1], resulting in a reduced quality of
life [2]. Several factors are thought to negatively influence
cognition in MS patients, such as depression [3], fatigue
[4], and sleep disturbances [5]. Approximately 50 % of the
patients with MS suffer from sleep disturbances (e.g.,
insomnia or sleep-disordered breathing) [6].
In healthy controls (HCs), proper sleep is important for
memory consolidation [7] and sleep deprivation has been
related to impaired functioning in various cognitive
domains [8]. The literature on sleep disturbances and
cognition in MS is scarce. One study showed an association
between sleep disturbances and a decline in sustained
attention [9], whereas another study related reduced sleep
efficiency to problems with information processing and
executive function [5].
On functional (f) magnetic resonance imaging (MRI),
the effects of sleep disturbances can be seen as
hypo-activation in medial and inferior prefrontal areas in subjects
with insomnia compared to HCs during a cognitive task,
which returned to normal values after sleep therapy [10]. In
addition, shallow sleep has been related to reduced
hippocampal activation [11], and the thalamus showed
decreased functional connectivity (FC) in sleep deprived
HCs [12].
In MS, damage to the hippocampus and thalamus (e.g.,
lesions and atrophy) is associated with worse cognition
[13, 14]. In HCs, both regions can be related to sleep and
cognition. In the present study, we investigated sleep
disturbances in MS in relation to cognitive functioning and
resting-state (RS) FC of the hippocampus and thalamus.
We hypothesize that sleep problems negatively influence
cognition and can be related to FC alterations of the
hippocampus and thalamus.
Materials and methods
All patients (n = 71; 47 female; mean disease duration
11.0 years) were diagnosed with clinically definite MS
according to the revised McDonald criteria [15]. On the day of
scanning, disease severity was measured using a questionnaire
based on the expanded disability status scale [16]. Age- and
sex matched HCs (n = 40; 26 female) were included.
Subjects included in this study are partly overlapping with a
previously reported fMRI study [17]. Exclusion criteria were
the presence or history of psychiatric or neurological diseases
(for patients: other than MS) and contra-indications for MRI.
All participants gave written informed consent prior to
participation. The institutional ethical review board approved the
study protocol and it has therefore been performed in
accordance with the ethical standards laid down in the 1964
Declaration of Helsinki.
Sleep disturbances
The Athens Insomnia Scale (AIS) is a self-report questionnaire,
validated in HCs, and was used to measure sleep disturbances
[18]. This questionnaire includes eight items on which a score
ranging from zero to three points (no to severe problems) can be
obtained for each item. As the eight-item version of the AIS
includes three items that can reflect MS symptoms independent
from sleep problems (e.g., fatigue during t (...truncated)