**4. Brain changes associated with OSA**

There is evidence of structural and functional brain changes in critical areas for cognition in patients with OSA. Numerous investigations have reported changes in the electroencephalogram of OSA patients compared with healthy individuals. These changes show abnormal cortical excitability associated with neurocognitive deficits [59, 60]. In the prefrontal model sleep disruption, intermittent hypoxemia, and hypercapnia observed in OSA produce cellular and biochemical stresses that alter neuronal and glial viability within prefrontal regions of the brain cortex, affecting the efficacy of restorative process occurring during sleep. This model explains the relationship between sleep fragmentation and nocturnal hypoxemia with predominantly frontal deficits. However, the neuroanatomic regions that have most commonly been reported in OSA are thalamus and frontoparietal cortex [61]. Degenerative areas in brain include: hippocampus (memory and new learning), the thalamus (sensory and motor signaling and in regulating sleep and alertness) and the amygdala (regulation of emotion) [16]. The findings in fMRI suggested a dysfunctional connectivity of the posterior default mode neuronal network and changes in network in the anterior insula, posterior-medial frontal cortex and thalamus (right amygdala-hippocampus complex and the insular cortex) [62, 63].

Several studies reported that OSA is a risk factor for cerebral small vessel disease (C-SVD). C-SVD is a group of pathologic processes that affect small arteries and veins, arterioles, and capillaries. Restricted blood flow in diseased small vessels, produce low perfusion pressure and hypoperfusion of the affected brain areas. Subsequently, chronic hypoperfusion develop ischemic C-SVD [64, 65]. Changes in white matter associated with OSA has also been reported. Degradation of multiple areas of subcortical tracts of the superior and inferior parietal lobe, deep frontal white matter and arcuate fasciculus. The white matter fiber integrity was recuperated after 12 months of CPAP treatment and this recuperation was associated with improvement in memory, attention, and executive functions [55]. The gray matter is also affected in patients with OSA. Some studies report that extent of gray matter volume loss increases correlated positively with OSA severity. Decreased gray matter has been observed in the frontal and parietal cortex, temporal lobe, anterior cingulate, hippocampus, and cerebellum [66, 67] (**Figure 1**).

**Figure 1.** *Magnetic resonance imaging in patient with cognitive impairment and OSA and in healthy individual.*
