Obstructive sleep apnea (OSA) is a disease of repeated episodes of upper airway obstruction during sleep, resulting in intermittent hypoxemia and arousal [
Neuroimaging studies have showed structural changes in the brains of individuals with OSA [
The purpose of our study is to investigate diffusion alterations in specific regions of the brain among morbid obese, obese, and nonobese patients with OSA and to show whether there is a relation between Body Mass Index (BMI) and ADC values in these patients.
A total of 65 patients (20 females, 45 males, mean age:
The BMI was calculated by dividing the weight in kilograms by the square of heighth in meters. BMI groups were defined using the World Healt Organization (WHO) classification system. The patients with BMI more than 30 kg/m² (group 1,
The Magnetic Resonance Imaging (MRI) examination consisted of routine imaging including DWI. MRI was performed on 1.5-T system (Siemens, Avanto, Erlangen, Germany). Fast spin echo T2WI (TR = 4530 ms, TE = 100 ms) in the axial and sagittal planes, T1WI (TR = 550 ms, TE = 20 ms) in the axial plane, and FLAIR images (TR = 8000 ms, TE = 90 ms) in the axial and coronal planes were obtained. For DWI, a single-shot spin echo-planar pulse sequence (TR = 6900 ms, TE = 89 ms, field of view (FOV) = 230 mm, matrix size = 128 × 128, number of acquisitions = 2, slice thickness = 5 mm, slice number = 25, slice orientation = axial plane, scan time = 8 s, and interslice gap = 1 mm) was used in all patients with two different
ADC maps show several ROIs: midbrain (1), amygdala (2), hippocampal gyrus (3), and occipital cortex (4) on (a); hypothalamus (5), insular (6), middle temporal (7), and parietal cortices (8) on (b).
ADC maps show several ROIs: orbitofrontal cortex (9), cingulate gyrus (10), genu (11) and splenium (12) of corpus callosum, caudate nucleus (13), putamen (14), thalamus (15), and posterior limb of internal capsula (16) on (a); dorsomedial (17) and dorsolateral (18) frontal cortices and frontal white matter (19) on (b).
All statistical analyses were performed using a commercially available SPSS release 20.0 software package (SPSS Inc., Chicago, IL, USA). The results were presented as the mean ± standard deviation (SD). To test differences between groups, Kruskal-Wallis variance analysis was used. The groups showed normal distribution. In evaluation of sociodemographic variables, ANOVA (Tukey’s test) was used. Student
Demographic information and clinical information were presented in Table
Demographic and clinical characteristics in patients with OSA.
Patients | Age | RDI | AI | HI |
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Group 1 |
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Subgroup 1 |
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Subgroup 2 |
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Group 2 |
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Group 1: total obese patients (BMI ≥ 30 kg/m²).
Subgroup 1: morbid obese patients.
Subgroup 2: obese patients.
Group 2: nonobese (control) patients.
RDI: respiratory disturbance index.
AI: apnea index.
HI: hypopnea Index.
Mean ADC values (
Locations | Group 1 ( |
Group 2 | ||
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Subgroup 1 |
Subgroup 2 |
Total | ||
Dentate nucleus |
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Cerebellar vermis |
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Cerebellar cortex |
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Amygdala |
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Midbrain |
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Hippocampal gyrus |
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Occipital cortex |
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Hypothalamus |
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Middle temporal cortex |
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Insular cortex |
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Parietal cortex |
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Orbitofrontal cortex |
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Cingulate gyrus |
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Posterior limb of internal capsula |
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Caudate nucleus |
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Globus pallidum |
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Putamen |
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Thalamus |
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Optic radiation |
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Genu of corpus callosum |
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Splenium of corpus callosum |
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Dorsomedial frontal cortex |
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Dorsolateral frontal cortex |
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Frontal white matter |
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Group 1: total obese patients (BMI ≥ 30 kg/m²).
Subgroup 1: morbid obese patients.
Subgroup 2: obese patients.
Group 2: nonobese (control) patients.
There was no significant difference between age, gender, RDI, and AI values of subgroup 1, subgroup 2, all obese group, and control group. There was a significant difference between HI values of morbid obese and control group (
The ADC values in hypothalamus (
(a) The figure shows that the ADC values (×10−6 mm²/s) in hypothalamus, insular cortex, parietal cortex, caudate nucleus, posterior limb of internal capsula, and frontal white matter were significantly increased in total obese patients compared to control group. (b) The figure shows that the ADC values (×10−6 mm²/s) in hypothalamus, insular cortex, parietal cortex, caudate nucleus, and frontal white matter were significantly higher in morbid obese compared to control group. (c) The figure shows that the ADC values (×10−6 mm²/s) in midbrain, hypothalamus, orbitofrontal cortex, and parietal cortex were significantly increased in morbid obese compared to obese patients.
The ADC values in hypothalamus (
The ADC values of midbrain (
The ADC values of frontal white matter (
In all obese patients with OSA (
There is no effect of age on ADC values in all groups including subgroups.
OSA is the most common type of apnea, and it develops gradually overtime. It is related to intermittent obstructions of upper airway throughout sleep. The prevalence of OSA in adult is 2–4% [
Excessive daytime sleepiness is one of the most frequent symptoms identified in patients with OSA. The residual sleepiness could be a posthypoxic injury phenomenon or a specific neuropsychological syndrome [
Obesity is the most important risk factor for OSA. The majority of adult patients with OSA are obese. The percentage of children diagnosed with OSA is increasing as obesity rate widened [
Until now, many patients with OSA were unable to appropriately fit into the MRI scanner. This limits interpretation regarding the interaction of OSA and obesity and/or any pathophysiological differences of OSA among obese and nonobese patients [
Advances in neuroimaging technology have given us the ability to evaluate the brain functions. DWI is an important tool in the neurosciences to understand the key structure-function relationship of the brain. In DWI, image contrast occurs via the molecular motion of water, which may be substantially altered in diseases [
Neuronal damage and vasogenic edema in the different brain regions of OSA patients due to intermittent hypoxia have been reported in the literature [
In our study, the ADC values of cognitive centers were significantly increased in morbid obese when compared to nonobese control patients with OSA. These findings pointed out that morbid obesity is associated with altered extracellular fluid (ECF)/intracellular fluid (ICF) ratio in cognitive centers. Moreover, the ADC values of midbrain, hypothalamus, orbitofrontal cortex, and parietal cortex were significantly increased in morbid obese when compared to obese patients with OSA. Moreover, demonstration of the positive correlation between BMI and ADC values in hypothalamus, orbitofrontal cortex, and parietal cortex supports the importance of diffusion alteration in obesity with OSA. Overall, our findings suggest that there is a parallel increase between BMI and altered fluid ECF/ICF ratio in different brain locations in overweighted patients with OSA. This may be due to vasogenic edema, gliosis, cell death, or metabolic changes. The mechanism is not yet clear in this study.
Excessive daytime sleepiness is the main cause of the neuropsychological deficits in patients with OSA and the comorbidities, such as cardiovascular disease, obesity, and physical inactivity usually are more important than the sleep apnea [
The recent study by Kumar et al. have shown a decrease in global and regional mean diffusivity in the brain in OSA [
We found microstructural changes in the brain in OSA patients which could be related to obesity and/or hypoxia, and increasing ADC values with increasing BMI. We hypothesize that the main reason of brain diffusion changes in patients with OSA could be obesity related. Although the mechanism is not yet clear, brain diffusion alteration in patients with OSA patients may help in the understanding of the underlying pathophysiology and guide new treatment strategies.
The authors declare that there is no conflict of interests regarding the publication of this paper.