title: Hippocampal substructural vulnerability to sleep disturbance and cognitive impairment in patients with chronic primary insomnia: magnetic resonance imaging morphometry.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Pointwise morphometry allowed for volume measurements of hippocampal regions on T1-weighted MRI.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Twenty-seven unmedicated patients (age: 51.2 ± 9.6 y) and 30 good sleepers as controls (50.4 ± 7.1 y).
  
  
  METHODS
  N/A.
  
  
  METHODS
  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 (|r| > 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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Joo EY, Kim H, Suh S, Hong SB. Hippocampal substructural vulnerability to sleep disturbance and cognitive impairment in patients with chronic primary insomnia: magnetic resonance imaging morphometry.
authors: Sleep Center, Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Seoul, Korea.
authors: Eun Yeon
authors: EY
authors: Joo
authors: Department of Neurology and Brain Imaging Center, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
authors: Hosung
authors: H
authors: Kim
authors: Korea University Ansan Hospital, Human Genome Institute, Korea University, Seoul, Korea ; Stanford University, Department of Psychiatry, Redwood City, CA.
authors: Sooyeon
authors: S
authors: Suh
authors: Sleep Center, Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Seoul, Korea.
authors: Seung Bong
authors: SB
authors: Hong
mesh_terms: D000328:Adult; D000368:Aged; D001284:Atrophy / Q000473:pathology; D016022:Case-Control Studies; D003071:Cognition; D003072:Cognition Disorders / Q000473:pathology* / Q000503:physiopathology*; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D055495:Neurogenesis; D009483:Neuropsychological Tests; D012892:Sleep Deprivation / Q000473:pathology / Q000503:physiopathology; D007319:Sleep Initiation and Maintenance Disorders / Q000473:pathology* / Q000503:physiopathology*; D013315:Stress, Psychological
keywords: chronic insomnia; hippocampus; memory; morphometry; sleep; surface analysis