The role of sleep on cognition and functional connectivity in patients with multiple sclerosis

Journal of Neurology, Oct 2016

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 functioning, but rather to subjective cognitive problems. In addition, sleep disturbances in MS seem to coincide with a specific pattern of decreased thalamic FC.

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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 - 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)


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Quinten van Geest, B. Westerik, Y. D. van der Werf, J. J. G. Geurts, H. E. Hulst. The role of sleep on cognition and functional connectivity in patients with multiple sclerosis, Journal of Neurology, 2017, pp. 72-80, Volume 264, Issue 1, DOI: 10.1007/s00415-016-8318-6