title: Hippocampal atrophy confounds template-based functional MR imaging measures of hippocampal activation in patients with mild cognitive impairment.
abstract: OBJECTIVE
  Functional MR imaging has been used to study patterns of hippocampal activation that distinguish pathologic from normal memory loss in the elderly population. Our objective was to assess whether hippocampal atrophy confounds measurements of hippocampal activation in subjects with mild cognitive impairment (MCI).
  
  
  METHODS
  Twenty subjects with MCI and 20 elderly control subjects with objectively normal memory were studied at 4T during a face-name paradigm designed to activate the hippocampus. Hippocampal activation was measured using 2 separate approaches: applying a preset region of interest (ROI) in standardized template space and applying a manually drawn ROI in native subject space. Pearson correlation coefficients were calculated to compare group-dependent relationships between hippocampal volume and activation. Analysis of covariance (ANCOVA) was performed to assess group differences in hippocampal activation during encoding and retrieval. Age and hippocampal volume were included as covariates, as was a term for the interaction between hippocampal volume and group.
  
  
  RESULTS
  When hippocampal activation was measured by the template-based method, the correlation coefficient in the right hippocampus of subjects with MCI but not control subjects during retrieval differed significantly from zero. There was a significant (P < .05) group-by-volume interaction in the ANCOVA model. No significant correlations or interactions were demonstrated when activation was measured in native subject space with manually drawn ROIs.
  
  
  CONCLUSIONS
  Our findings suggest a potential confounding relationship between hippocampal volume and activation for subjects with MCI in template-based analyses. Template-based measures of hippocampal activation that do not adequately account for hippocampal atrophy should be used with caution in patients with MCI.
authors.affiliation: Department of Radiology, Brain Imaging and Analysis Center, Duke University Medical Center, Durham, NC, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Sandstrom
authors.forename: S
authors.initials: S
authors.lastname: Krishnan
authors.forename: M J
authors.initials: MJ
authors.lastname: Slavin
authors.forename: T-T T
authors.initials: TT
authors.lastname: Tran
authors.forename: P M
authors.initials: PM
authors.lastname: Doraiswamy
authors.forename: J R
authors.initials: JR
authors.lastname: Petrella
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000503:physiopathology*; D016477:Artifacts; D001245:Association Learning / Q000502:physiology; D001284:Atrophy; D005260:Female; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008432:Mathematical Computing; D011939:Mental Recall / Q000502:physiology; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D010364:Pattern Recognition, Visual / Q000502:physiology; D012016:Reference Values; D012984:Software; D014706:Verbal Learning / Q000502:physiology