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Yahui Wan,1 Mengdi Lv,2 Kaili Zhou,1 Zheng Li,3 Xueyun Du,1 Wei Wu,4 Rong Xue4 1Departments of Neurology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, 300308, People’s Republic of China; 2Departments of Neurology, Tianjin First Central Hospital, Tianjin, 300190, People’s Republic of China; 3Departments of Neurology, Binhai Hospital, Peking University, Tianjin, 300450, People’s Republic of China; 4Departments of Neurology, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of ChinaCorrespondence: Rong Xue, Departments of Neurology, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China, Email xuerong1403@126.comPurpose: To evaluate the correlation between sleep microstructure, autonomic nervous system activity, and neuropsychological characteristics in chronic insomnia (CI) patients with obstructive sleep apnea (OSA).Patients and Methods: Forty-five CI-OSA patients, forty-six CI patients and twenty-two matched healthy control subjects (HCs) were enrolled. CI-OSA patients were then divided into two groups: mild OSA and moderate-to-severe OSA. All participants completed neuropsychological tests, which included the Hamilton Depression and Anxiety Scales (HAMD and HAMA), the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale (ESS), and the Mini-mental State Examination (MMSE). The autonomic nervous system activity and sleep microstructure were examined by the PSM-100A.Results: The CI-OSA patients exhibited higher scores on the PSQI, ESS, ISI, HAMA, and HAMD than HCs and CI patients (all p < 0.01). The CI-OSA patients had a lower proportion of stable sleep, REM sleep and a higher proportion of unstable sleep ratio (all p < 0.01) than HCs and CI patients (all p < 0.01). The CI-OSA patients had higher ratios of LF and LF/HF, and lower ratios of HF and Pnn50% (all p < 0.01) than HCs and CI patients (all p < 0.01). Compared to CI-mild OSA patients, the CI-moderate-to-severe OSA patients presented with a higher ESS scores, higher ratios of LF and LF/HF, and lower ratios of HF (all p < 0.05). In CI-OSA patients, higher HAMD scores were correlated with decreased MMSE scores (r=− 0.678, p < 0.01). A higher LF ratio was correlated with higher HAMD and HAMA scores (r=0.321, p=0.031, r =0.449, p =0.002), and a higher HF ratio was correlated with lower HAMD and HAMA scores (r=− 0.321, P =0.031, r =− 0.449, p =0.002).Conclusion: OSA exacerbates the abnormalities of sleep microstructure and the autonomic nervous dysfunction in CI patients. Dysfunction of the autonomic nervous system could contribute to mood deterioration in CI with OSA patients.Keywords: chronic insomnia, obstructive sleep apnea, OSA, depression, sleep microstructure, autonomic function