Hippocampal Substructural Vulnerability to Sleep Disturbance and Cognitive Impairment in Patients with Chronic Primary Insomnia: Magnetic Resonance Imaging Morphometry

Study Objectives: Despite compelling evidence from animal studies indicating hippocampal subfield-specific vulnerability to poor sleep quality and related cognitive impairment, there have been no human magnetic resonance imaging (MRI) studies investigating the relationship between hippocampal subfield volume and sleep disturbance. Our aim was to investigate the pattern of volume changes across hippocampal subfields in patients with primary insomnia relative to controls. Design: Pointwise morphometry allowed for volume measurements of hippocampal regions on T1-weighted MRI. Setting: University hospital. Patients: Twenty-seven unmedicated patients (age: 51.2 +/- 9.6 y) and 30 good sleepers as controls (50.4 +/- 7.1 y). Interventions: N/A. Measurements: We compared hippocampal subfield volumes between patients and controls and correlated volume with clinical and neuropsychological features in patients. Results: Patients exhibited bilateral atrophy across all hippocampal subfields (P < 0.05 corrected). Cornu ammonis (CA) 1 subfield atrophy was associated with worse sleep quality (higher Pittsburgh Sleep Quality Index and higher arousal index of polysomnography) (r < -0.45, P < 0.005). The volume of the combined region, including the dentate gyrus (DG) and CA3-4, negatively correlated with verbal memory, verbal information processing, and verbal fluency in patients (vertical bar r vertical bar > 0.45, P < 0.05). Hemispheric volume asymmetry of this region (left smaller than right) was associated with impaired verbal domain functions (r = 0.50, P < 0.005). Conclusion: Hippocampal subfield atrophy in chronic insomnia suggests reduced neurogenesis in the dentate gyrus (DG) and neuronal loss in the cornu ammonis (CA) subfields in conditions of sleep fragmentation and related chronic stress condition. Atrophy in the CA3-4-DG region was associated with impaired cognitive functions in patients. These observations may provide insight into pathophysiological mechanisms that make patients with chronic sleep disturbance vulnerable to cognitive impairment.