## 4 Discussion  
In this pilot-study of treatment naive middle-aged to older males with moderate to severe OSA, we observed correlations between the insomnia severity index with decreased attention. In addition, we observed a positive correlation between the insomnia severity index with the anterior cingulate gyrus. Similar to our findings, patients with primary insomnia had increased brain volumes in the anterior cingulate gyrus [39], which has been associated with increased sleep-onset latency and wake after sleep onset [39], The anterior cingulate gyrus help process cognitive and emotional information [39], which could help further explain cognitive difficulties in OSA patients with possible comorbid insomnia. While most of our OSA patients had insomnia complaints, the small sample size and pilot nature of our study precluded us from disentangling nocturnal from daytime complaints, when using the insomnia severity index. Our findings could be explained by sleep fragmentation and associated sleep disruption in OSA. As suggested by others, future studies should isolate insomnia complaints in OSA patients, using the nocturnal sub-score of the insomnia severity index. \begin{table}
\begin{tabular}{c c c c c c c c} \hline \hline
**MRI Brain** & **Anterior** & **Total Cortical** & **Medial** & **Middle** & **Precuneus** & **Interior** \\
**Volumes** & **Cingulate** & **Cotrex** & **Volume** & **Cotrex** & **Cotrex** & **Cotrex** & **Cotrex** \\ \hline
**Insomnia** & & & & & & & \\
**severity index** & & & & & & & \\ \hline
**Average oxygen** & & & & & & & \\
**saturation** & - & 0.65 (0.06) & 0.82 (0.003) & 0.64 (0.07) & 0.77 (0.01) & 0.64 (0.07) & - \\
**during sleep** & & & & & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Correlations between insomnia, sleepiness and oxygen during sleep with brain volumes. We did not observe a correlation between the apnea-hypopnea index and brain volumes. Multiple studies describe associations between the apnea-hypopnea index and either decreased or increased brain volumes [40]. The apnea-hypopnea index is the main diagnostic and treatment metric for OSA. Of interest, the average sleep oxygen saturation correlated with lower brain volumes. In a large population-based study, average oxygen saturation during sleep correlated with lower brain volumes in the hippocampus-amygdala complex and other cortical regions sensitive to low oxygen saturation [41]. These findings suggest that nocturnal oxygen saturation could be a better metric to study brain health in OSA patients. In addition, we observed that daytime sleepiness, as measured by the Epworth sleepiness scale, had positive correlations with the lateral ventricles, suggesting an increment in ventricular volume with increase daytime sleepiness. Human and animal studies suggest that daytime sleepiness could be the manifestation of hypoxemia-related brain damage [42; 43; 44; 45], in OSA. Importantly, increased ventricular volumes was associated with a 46% increased dementia-risk in the \"Atherosclerosis Risk in Communities Study\" cohort [46]. Our findings implicate gross cerebral compromise, and more specifically, the potential impact to the medial temporal lobe, where both learning and general memory functions reside [47]. The correlations between the insomnia severity index and the Epworth sleepiness scale with cognitive and neuroimaging measures suggest a dysfunction of the frontal-temporal network. Our findings suggest that advanced neuroimaging measures of brain health and cognition can serve as outcomes in OSA patients. Of importance, symptoms and metrics beyond the apnea-hypopnea index are necessary to identify at risk individuals, as well as to determine the interventions that could help reduce the impact of age-related cognitive decline and dementia in OSA patients. The strengths of our pilot study include the systematic measurement of cognition and neuroimaging obtained during the same research day, along with validated sleep questionnaires.