White Matter and Hippocampal Volume Predict the Risk of Dementia in Patients with Cerebral Small Vessel Disease: The RUN DMC Study

Article type: Research Article

Authors: van Uden, Ingeborg W.M.^a | van der Holst, Helena M.^a | Tuladhar, Anil M.^a | van Norden, Anouk G.W.^b | de Laat, Karlijn F.^c | Rutten-Jacobs, Loes C.A.^h | Norris, David G.^{d; e} | Claassen, Jurgen A.H.R.^f | van Dijk, Ewoud J.^a | Kessels, Roy P.C.^g | de Leeuw, Frank-Erik^{a; *}

Affiliations: [a] Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Department of Neurology, Nijmegen, The Netherlands | [b] Department of Neurology, Amphia ziekenhuis Breda, The Netherlands | [c] Department of Neurology, HagaZiekenhuis Den Haag, The Netherlands | [d] Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands | [e] Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Essen, Germany | [f] Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Department of Geriatrics, Nijmegen, The Netherlands | [g] Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Department of Medical Psychology, Nijmegen, The Netherlands | [h] University of Cambridge, Department of Clinical Neurosciences, Neurology Unit, Cambridge, UK

Correspondence: [*] Correspondence to: Frank-Erik de Leeuw, MD, PhD, Radboud University Medical Center, Department of Neurology, Reinier Postlaan 4, PO-box 9101, 6500 HB Nijmegen, The Netherlands.Tel.: +31 243613396; Fax: +31 243541122; E-mail: [email protected]

Abstract: Background:The relationship between cerebral small vessel disease (SVD) and dementia has been studied without considering white matter (WM) volume, the microstructural integrity of the WM surrounding the SVD, and grey matter (GM). Objective:We prospectively investigated the relationship between these structures and the risk of dementia, and formed a prediction model to investigate which characteristics (macro- or microstructural) explained most of the variance. Methods:The RUN DMC study is a prospective cohort study among 503 non-demented participants with an age between 50 and 85 years at baseline, with baseline assessment in 2006 and follow-up assessment in 2012. Two were lost to follow-up (yielding a 99.6% response-rate). Cox regression analysis was used, to calculate hazard ratios for dementia, of baseline MRI characteristics. Tract-Based Spatial Statistics (TBSS) analysis was used to assess the added value of microstructural integrity of the WM. Results:Mean age at baseline was 65.6 years (SD 8.8) and 56.8% was male. 43 participants developed dementia (8.6% ), resulting in a 5.5-year cumulative risk of 11.1% (95% CI 7.7–14.6). Low WM and hippocampal volume are significant predictors for dementia. WM, WM hyperintensities, and hippocampal volume explained most of the variance. TBSS analyses showed no additional value of diffusion parameters. Conclusions:WM and hippocampal volume were the main predictors for the development of incident dementia at 5-year follow-up in elderly with SVD. There was no additional diagnostic value of the diffusion tensor imaging parameters on top of the macrostructural characteristics.

Keywords: Dementia, diffusion tensor imaging, elderly, hippocampal volume, small vessel disease, Magnetic resonance imaging, white matter

DOI: 10.3233/JAD-150573

Journal: Journal of Alzheimer's Disease, vol. 49, no. 3, pp. 863-873, 2016