title: Diffusion tensor imaging of the hippocampus predicts the risk of dementia; the RUN DMC study.
abstract: BACKGROUND
  Cerebral small vessel disease is one of the most important risk factors for dementia, and has been related to hippocampal atrophy, which is among the first observed changes on conventional MRI in patients with dementia. However, these volumetric changes might be preceded by loss of microstructural integrity of the hippocampus for which conventional MRI is not sensitive enough. Therefore, we investigated the relation between the hippocampal diffusion parameters and the risk of incident dementia, using diffusion tensor imaging, independent of hippocampal volume.
  
  
  METHODS
  The RUNDMC study is a prospective study among 503 elderly with small vessel disease, without dementia, with 5 years follow-up in 2012 (99.6% response-rate). Cox regression analysis was performed to calculate hazard ratios for dementia, of fractional anisotropy and mean diffusivity within the hippocampus, adjusted for demographics, hippocampal volume, and white matter. This was repeated in participants without evident hippocampal volume loss, because in these participants the visible damage might not yet have already started, whereas damage might have started on a microstructural level.
  
  
  RESULTS
  43 participants developed dementia (8.6%), resulting in a 5.5-year cumulative risk of 11.1% (95%CI 7.7-14.6). Higher mean diffusivity was associated with an increased 5-year risk of dementia. In the subgroup of participants with the upper half hippocampal volume, higher hippocampal mean diffusivity, more than doubled the 5-year risk of dementia.
  
  
  CONCLUSIONS
  This is the first prospective study showing a relation between a higher baseline hippocampal mean diffusivity and the risk of incident dementia in elderly with small vessel disease at 5-year follow-up, independent of hippocampal volume and white matter volume.
authors.affiliation: Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Department of Neurology, The Netherlands.
authors.forename: I W M
authors.initials: IW
authors.lastname: van Uden
authors.affiliation: Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Department of Neurology, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Tuladhar
authors.affiliation: Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Department of Neurology, The Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: van der Holst
authors.affiliation: Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Department of Neurology, The Netherlands.
authors.forename: E M C
authors.initials: EM
authors.lastname: van Leijsen
authors.affiliation: Department of Neurology, Amphia Ziekenhuis Breda, The Netherlands.
authors.forename: A G W
authors.initials: AG
authors.lastname: van Norden
authors.affiliation: Department of Neurology, HagaZiekenhuis Den Haag, The Netherlands.
authors.forename: K F
authors.initials: KF
authors.lastname: de Laat
authors.affiliation: Department of Clinical Neurosciences, Neurology Unit, University of Cambridge, United Kingdom.
authors.forename: L C A
authors.initials: LC
authors.lastname: Rutten-Jacobs
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, The Netherlands.|Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, D-45141, Germany.
authors.forename: D G
authors.initials: DG
authors.lastname: Norris
authors.affiliation: Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Department of Geriatrics, The Netherlands.
authors.forename: J A H R
authors.initials: JA
authors.lastname: Claassen
authors.affiliation: Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Department of Neurology, The Netherlands.
authors.forename: E J
authors.initials: EJ
authors.lastname: van Dijk
authors.affiliation: Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Department of Geriatrics, The Netherlands.|Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Department of Medical Psychology, The Netherlands.
authors.forename: R P C
authors.initials: RP
authors.lastname: Kessels
authors.affiliation: Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Department of Neurology, The Netherlands.
authors.forename: F-E
authors.initials: FE
authors.lastname: de Leeuw
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016880:Anisotropy; D059345:Cerebral Small Vessel Diseases / Q000150:complications; D003704:Dementia / Q000209:etiology / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D007839:Functional Laterality; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012044:Regression Analysis
keywords: cerebral small vessel disease; dementia; diffusion tensor imaging; elderly; hippocampus; imaging; magnetic resonance imaging