title: Hippocampal disconnection in early Alzheimer's disease: a 7 tesla MRI study.
abstract: BACKGROUND
  In patients with Alzheimer's disease (AD), atrophy of the entorhinal cortex (ERC) and hippocampal formation may induce degeneration of connecting white matter tracts.
  
  
  OBJECTIVE
  We examined the association of hippocampal subfield and ERC atrophy at 7 tesla MRI with fornix and parahippocampal cingulum (PHC) microstructure in patients with early AD.
  
  
  METHODS
  Twenty-five patients with amnestic mild cognitive impairment (aMCI) (n = 15) or early AD (n = 10) and 17 controls underwent 3 tesla diffusion MRI to obtain fractional anisotropy (FA) of the fornix and PHC and 7 tesla MRI to obtain ERC and hippocampal subfield volumes. Linear regression analyses were performed, adjusted for age, gender, and intracranial volume.
  
  
  RESULTS
  Fornix FA was significantly lower and subiculum, cornu ammonis (CA) 1, and dentate gyrus &CA4 volume were significantly smaller in patients with MCI or AD as compared to controls. In patients with MCI or AD, fornix FA was positively associated with subiculum volume (β = 0.53, 95% CI 0.10; 0.96), but not with ERC/other subfield volumes. PHC FA was not associated with ERC/subfield volumes.
  
  
  CONCLUSIONS
  These findings indicate that in early AD subiculum atrophy is associated with lower FA of the fornix, which primarily consists of axons originating in the subiculum. This suggests that degeneration of subicular cell bodies and their axons are related processes in early AD.
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, UMC Utrecht, Utrecht, The Netherlands Julius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Laura E M
authors.initials: LE
authors.lastname: Wisse
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, UMC Utrecht, Utrecht, The Netherlands J. Philip Kistler Stroke Center, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: Yael D
authors.initials: YD
authors.lastname: Reijmer
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Annemieke
authors.initials: A
authors.lastname: ter Telgte
authors.affiliation: Image Sciences Institute, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Hugo J
authors.initials: HJ
authors.lastname: Kuijf
authors.affiliation: Image Sciences Institute, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: Leemans
authors.affiliation: Department of Radiology, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Luijten
authors.affiliation: Department of Geriatrics, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Huiberdina L
authors.initials: HL
authors.lastname: Koek
authors.affiliation: Julius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Mirjam I
authors.initials: MI
authors.lastname: Geerlings
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Geert Jan
authors.initials: GJ
authors.lastname: Biessels
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D016880:Anisotropy; D001284:Atrophy; D060825:Cognitive Dysfunction / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000295:instrumentation; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008297:Male; D009929:Organ Size
keywords: Alzheimer's disease; diffusion magnetic resonance imaging; fornix; hippocampus; mild cognitive impairment; subiculum