title: Functional implications of hippocampal degeneration in early Alzheimer's disease: a combined DTI and PET study.
abstract: OBJECTIVE
  Hypometabolism of the posterior cingulate cortex (PCC) in early Alzheimer's disease (AD) is thought to arise in part due to AD-specific neuronal damage to the hippocampal formation. Here, we explored the association between microstructural alterations within the hippocampus and whole-brain glucose metabolism in subjects with AD, also in relation to episodic memory impairment.
  
  
  METHODS
  Twenty patients with early AD (Mini-Mental State Examination 25.7 ± 1.7) were studied with [(18)F]fluorodeoxyglucose (FDG) positron emission tomography and diffusion tensor imaging. Episodic memory performance was assessed using the free delayed verbal recall task (DVR). Voxel-wise relative FDG uptake was correlated to diffusivity indices of the hippocampus, followed by extraction of FDG uptake values from significant clusters. Linear regression analysis was performed to test for unique contributions of diffusivity and metabolic indices in the prediction of memory function.
  
  
  RESULTS
  Diffusivity in the left anterior hippocampus negatively correlated with FDG uptake primarily in the left anterior hippocampus, parahippocampal gyrus and the PCC (p < 0.005). The same correlation pattern was found for right hippocampal diffusivity (p < 0.05). In linear regression analysis, left anterior hippocampal diffusivity and FDG uptake from the PCC cluster were the only significant predictors for performance on DVR, together explaining 60.6% of the variance. We found an inverse association between anterior hippocampal diffusivity and PCC glucose metabolism, which was in turn strongly related to episodic memory performance in subjects with early AD.
  
  
  CONCLUSIONS
  These findings support the diaschisis hypothesis of AD and implicate a dysfunction of structures along the hippocampal output pathways as a significant contributor to the genesis of episodic memory impairment.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Untere Zahlbacher Str. 8, 55131 Mainz, Germany. igor.yakushev@uni-mainz.de
authors.forename: Igor
authors.initials: I
authors.lastname: Yakushev
authors.forename: Matthias
authors.initials: M
authors.lastname: Schreckenberger
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Müller
authors.forename: Ingrid
authors.initials: I
authors.lastname: Schermuly
authors.forename: Paul
authors.initials: P
authors.lastname: Cumming
authors.forename: Peter
authors.initials: P
authors.lastname: Stoeter
authors.forename: Alex
authors.initials: A
authors.lastname: Gerhard
authors.forename: Andreas
authors.initials: A
authors.lastname: Fellgiebel
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D059907:Functional Neuroimaging / Q000379:methods; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013382:Subtraction Technique
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose