title: Atrophy of presubiculum and subiculum is the earliest hippocampal anatomical marker of Alzheimer's disease.
abstract: BACKGROUND
  There is no consensus about which hippocampal subfields become atrophic earliest in the course of Alzheimer's disease (AD).
  
  
  METHODS
  Thirty AD patients, 41 mild cognitive impairment (MCI) patients, and 38 healthy controls (HCs) underwent cerebral magnetic resonance imaging (with an automated segmentation protocol for the volumetric analysis of hippocampal subfields) and a test of immediate and delayed recall of a 15-word list.
  
  
  RESULTS
  The volumes of the presubiculum and subiculum presented the most remarkable reduction in the patient's groups. In the MCI group, only the volumes of presubiculum and subiculum predicted performance on the memory tests. In AD patients, the volumes of all hippocampal subfields (with the notable exception of the CA1) predicted memory scores.
  
  
  CONCLUSIONS
  Our data point to a prevalent atrophy of the presubicular-subicular complex from the early phases of AD. This finding is consistent with neuropathological observations in AD patients and probably reflects the severe degeneration of the perforant pathway while penetrating the hippocampus through the subicular field in its course from the entorhinal cortex to the dentate gyrus.
authors.affiliation: Department of Neuroscience, Tor Vergata University, Rome, Italy; Department of Clinical and Behavioral Neurology, Santa Lucia Foundation, Rome, Italy.
authors.forename: Giovanni A
authors.initials: GA
authors.lastname: Carlesimo
authors.affiliation: Department of Clinical and Behavioral Neurology, Santa Lucia Foundation, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Piras
authors.affiliation: Department of Clinical and Behavioral Neurology, Santa Lucia Foundation, Rome, Italy.
authors.forename: Maria Donata
authors.initials: MD
authors.lastname: Orfei
authors.affiliation: Department of Clinical and Behavioral Neurology, Santa Lucia Foundation, Rome, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Iorio
authors.affiliation: Department of Neuroscience, Tor Vergata University, Rome, Italy; Department of Clinical and Behavioral Neurology, Santa Lucia Foundation, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.affiliation: Department of Clinical and Behavioral Neurology, Santa Lucia Foundation, Rome, Italy; Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Spalletta
keywords: Alzheimer's disease; Brain atrophy; Memory; Mild cognitive impairment; Structural MRI