Cognitive profile and brain morphological changes in obstructive sleep apnea
Research Highlights
► Multiple structural changes in OSA patients were found using brain MRI analysis. ► Significant cognitive impairment in OSA independent of cardiovascular comorbidities. ► Chronic intermittent hypoxemia in OSA patients expedites the process of brain aging.
Introduction
Obstructive sleep apnea (OSA) is characterized by repetitive episodes of complete (apnea) or partial (hypopnea) obstruction of the upper airway during sleep. These episodes result in decreased arterial oxygen saturation and transient arousals with marked disruption of normal sleep architecture (American Academy of Sleep Medicine, 1999). Excessive daytime sleepiness (EDS), fatigue and neuropsychological impairments are common clinical features in individuals with OSA. OSA is accompanied by impairment in several cognitive domains, including attention and vigilance decrements, memory gaps, and abnormalities in executive functions (Kim et al., 1997, Ferini-Strambi et al., 2003, Saunamaki and Jehkonen, 2007), although the reported presence and degree of such impairment shows great variability between studies (Décary et al., 2000, Aloia et al., 2004). These functional alterations are likely related to structural tissue damage and metabolic stress occurring in different brain tissue compartments and neural structures. Previous structural neuroimaging studies in patients with OSA have reported inconsistent findings. Although routine magnetic resonance imaging (MRI) often fails to demonstrate obvious cerebral damage (Davies et al., 2001), a higher prevalence of silent cerebrovascular lesions has been recently reported in patients with moderate-severe OSA (Nishibayashi et al., 2008). More sensitive and quantitative MRI techniques can reveal structural alterations in specific brain regions implicated in cognitive functions. Such alterations were detected both in white matter (WM) using diffusion tensor imaging (Macey et al., 2008) and in several gray matter (GM) regions using voxel-based morphometry (VBM) (Macey et al., 2002, Morrell et al., 2003, Yaouhi et al., 2009, Joo et al., 2010). However, other researchers have not confirmed the VBM findings in OSA patients (O'Donoghue et al., 2005), probably because more stringent and conservative statistical methods were applied. VBM is used in GM volume studies to detect regional group differences in tissue volume, density or concentration, and to investigate correlations between regional GM measures and clinical or neuropsychological variables (Ashburner and Friston, 2000, Good et al., 2001). We have undertaken a similar approach and, in addition, we performed a hypothesis-driven segmentation of cortical and subcortical structures with the following objectives: (i) to evaluate brain structural changes and neurocognitive profile in a group of moderate-to-severe OSA individuals compared to a control population; (ii) to assess the relationship between MRI outcome variables and neuropsychological tests, as well as nocturnal respiratory data.
Section snippets
Subjects
The study cohort comprised thirty subjects, sixteen affected by OSA and fourteen normal controls. Sixteen newly diagnosed right-handed patients affected by moderate-to-severe OSA (mean apnea-hypopnea index, AHI, [standard deviation, SD]: 52.5 [26] events/hour) were enrolled (13 males and 3 females; mean age [SD]: 55.8 [6.7] years) (Table 1). All patients were untreated for OSA. Twelve of them (75%) had severe OSA (AHI of 31.6 to 106.3/h, mean [SD]: 63.3 [20.3]/h), while the remaining four (25%)
Subjects characteristics
Subjects with OSA and controls had similar age and comparable representation of the two genders. Presence of more men than women in the study cohort reflects the higher prevalence of OSA among men in the general population (Young et al., 1993). Patients and controls differed significantly for BMI and ESS scores (p < 0.01). Despite a higher prevalence of comorbidities (hypertension, diabetes, hypercholesterolemia, history of smoking and medication intake) in the OSA group, the differences with the
Discussion
In the present study, we found multiple structural changes in OSA patients using different quantitative approaches of MRI analysis. VBM showed a significant GM reduction in right and left hippocampal volumes in OSA patients compared to controls. This finding was confirmed for the right hippocampus also by the volumetric analysis. It can be argued that VBM is a more sensitive technique to show mild parenchymal damage not yet resulting in a loss of volume detectable by automated parcellation and
Conclusions
Our findings confirm that moderate-severe OSA can be accompanied by significant cognitive impairment. The brain image analysis performed using different techniques highlighted the presence of tissue damage in regions involved in several cognitive domains. Such damage appeared to be independent of differences in age, gender, use of tobacco and cardiovascular comorbidities. Therefore the presence of OSA could be seen as a factor which expedites the process of brain aging by increasing the
Conflict of interest statement
Dr. Torelli has no conflict of interest.
Dr. Moscufo has no conflict of interest.
Dr. Garreffa has no conflict of interest.
Dr. Placidi has no conflict of interest.
Dr. Romigi has no conflict of interest.
Dr. Zannino has no conflict of interest.
Dr. Bozzali has no conflict of interest.
Dr. Fasano has no conflict of interest.
Dr. Giulietti has no conflict of interest.
Dr. Djonlagic has no conflict of interest.
Dr. Malhotra has received consulting and/or research income from Philips, Pfizer, Merck,
Acknowledgments
This study was supported by NIH grants R01 HL 090897, R01 HL085188, K24 HL 093218, 1 P01 HL 095491, R01 AG022092-01, PO1 AG004390, and AHA 0840159N and the American Sleep Medicine Foundation.
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