Hypertension is Related to the Microstructure of the Corpus Callosum: The RUN DMC Study

Issue title: Physiopathology of Vascular Risk Factors in Alzheimer's Disease

Guest editors: Jack de la Torre

Article type: Research Article

Authors: Gons, Rob A.R.^{a; b} | van Oudheusden, Lucas J.B.^a | de Laat, Karlijn F.^a | van Norden, Anouk G.W.^a | van Uden, Inge W.M.^a | Norris, David G.^c | Zwiers, Marcel P.^d | van Dijk, Ewoud^a | de Leeuw, Frank-Erik^{a; *}

Affiliations: [a] Department of Neurology, Center for Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands | [b] Department of Neurology, Catharina Hospital, Eindhoven, The Netherlands | [c] Center for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands | [d] Department of Psychiatry, Center for Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Correspondence: [*] Correspondence to: F.-E. de Leeuw, MD, PhD, Department of Neurology, Center for Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Tel.: +31 243613396; Fax: +31 243541122; E-mail: [email protected].

Abstract: Vascular factors play a role in the etiology of Alzheimer's disease (AD), presumably due to emergence of white matter lesions. However, important white matter structures involved in the etiology of AD, including the corpus callosum (CC), remain invariably free from macroscopical white matter lesions, although loss of microstructural integrity assessed with diffusion tensor imaging (DTI) has been described in the CC. Vascular factors have been related to these microstructural white matter changes too, but little is known about their effect on the CC. In 499 subjects with cerebral small vessel disease, aged 50–85 years, we cross-sectionally investigated the relation between hypertension, hypertension treatment status, the microstructural integrity of the CC using DTI, and the attendant cognitive performance. Fractional anisotropy and mean diffusivity were calculated in four substructures of the CC (genu, anterior body, posterior body, and splenium). Differences between groups were calculated with analysis of variance, adjusted for age, gender, and cardiovascular risk factors. Compared with normotensive subjects, hypertensive subjects had a lower fractional anisotropy in the splenium and a significant higher mean diffusivity in both the anterior body and the splenium; this was most noticeable in treated uncontrolled hypertensive subjects. Furthermore we found that microstructural integrity of the CC was related to global cognition. Of this relation, 14 to 60% was explained by the mediating effect of small vessel disease elsewhere in the white matter. Our findings indicate that adequate blood pressure treatment might postpone these changes and the attendant cognitive dysfunction.

Keywords: Cerebral small vessel disease, cognition, corpus callosum, diffusion tensor imaging, hypertension, white matter

DOI: 10.3233/JAD-2012-121006

Journal: Journal of Alzheimer's Disease, vol. 32, no. 3, pp. 623-631, 2012