Elsevier

Neurobiology of Aging

Volume 33, Issue 5, May 2012, Pages 1002.e29-1002.e36
Neurobiology of Aging

Abstracts of online article
Longitudinal changes of cortical morphology in CADASIL

https://doi.org/10.1016/j.neurobiolaging.2011.09.013Get rights and content

Abstract

In CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy), a genetic model of subcortical ischemic vascular dementia (SIVD), clinical status was previously found related to cortex morphology. In the present report, alterations of cortex morphology and their links to clinical worsening were investigated in 190 CADASIL patients followed during 24.4 months. Linear models were used to test relationships between: (1) clinical worsening and changes of depth of cortical sulci and of cortical thickness; (2) alterations of cortical morphology and changes of volume of white matter hyperintensities (WMHv) and of lacunar lesions (LLv). Reduction of sulcal depth was independently associated with increased time to complete trail making test A and B (p < 0.0001 and p = 0.004) and that of cortical thickness to increased disability (modified Rankin's scale, p = 0.008), while brain atrophy was only related to global cognitive worsening (Mattis dementia rating scale, p = 0.002). The impact of volume of lacunar lesions on cortical alterations was larger than that of volume of white matter hyperintensities. Cortical alterations, mainly related to lacunar lesions, evolve parallel to clinical worsening. These results further support the eventual role of cortical alterations in subcortical ischemic vascular dementia.

Introduction

Several authors have previously emphasized the importance of cortical damage in CADASIL (Viswanathan et al., 2006) and in various small vessel diseases of the brain (SVDB) (Kövari et al., 2004; Sonnen et al., 2007, Soontornniyomkij et al., 2010). While the detailed evaluation of cortical microstructure remains out of reach in vivo, the improvement of magnetic resonance imaging (MRI) scanners together with the development of new postprocessing techniques allows now to investigate different characteristics of the cerebral cortex in SVDB (Magnotta et al., 1999, Mangin et al., 2010, Salat et al., 2004). We have recently proposed and validated different tools to evaluate the cortex morphology using MRI in CADASIL, particularly in the context of low gray/white contrast and high burden of white matter lesions (Jouvent et al., 2008, Mangin et al., 2010). In a cross-sectional study of 69 affected individuals, we previously observed that both cognitive scores and disability scales were associated with the depth of several cortical sulci (Jouvent et al., 2008) in line with other cortical measures obtained in sporadic SVDB (Preul et al., 2005, Wen et al., 2006). Thus, the assessment of cortical morphology may reliably reflect the severity of SVDB.

In the present large 2-center cohort study of CADASIL patients, we aimed to determine whether changes of the cortical morphology could be detected with MRI over a follow-up period of 18 to 36 months and whether these changes are actually associated with clinical worsening.

Section snippets

Subjects

Two hundred eighty-eight consecutive subjects (183 from Paris and 105 from Munich) aged older than 18 years, were recruited in an ongoing cohort study of CADASIL patients at Lariboisière (Paris) or Ludwig-Maximilians-Universität (Munich) hospitals between October 2003 and April 2009. All participants harbored a typical mutation of the Notch3 gene (Chabriat et al., 2009). At time of this study, 208 patients already had their second visit 18 months after inclusion, and 124 their third visit after

Results

Results of 10 of the 208 patients (7 from Paris and 3 from Munich) were excluded from analyses due to incomplete dataset (3), presence of a large territorial infarction (3), or insufficient quality caused by movement artifacts (4). For 8 more patients, sulci reconstruction failed repeatedly, leaving 190 subjects with available data at the second visit (18 months) and 106 at the second and third visits (18 and 36 months respectively). Mean follow-up duration for the 190 patients was 24.4 months.

Discussion

To our knowledge, this is the first longitudinal study of cortical morphological alterations in SVDB. The use of dedicated postprocessing algorithms allowed the detection of significant alterations of cortical morphology and structure that evolve parallel to the clinical worsening in a large cohort of CADASIL patients. These results are in line with a previous cross-sectional study of sulcal morphology obtained in a smaller group of CADASIL patients (Jouvent et al., 2008), as well as with

Disclosure statement

None of the authors reports any conflict of interest.

Independent ethics committees gave their approval for the study in each center.

Acknowledgements

The authors thank Nassirah Alili, Jocelyne Ruffié, and Solange Hello for their strong involvement in the follow-up of patients, and Denis Rivière, Matthieu Perrot, and Pauline Roca for the methodological development dedicated to the study of cortical folding.

This work was supported by a PHRC grant AOR 02-001 (DRC/APHP), Association de Recherche en Neurologie VAsculaire (ARNEVA), Hôpital Lariboisière, France, and E.J. was supported by a grant from the “Fonds d'Etude et de Recherche du Corps

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