title: Predictors of Clinical Worsening in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy: Prospective Cohort Study.
abstract: OBJECTIVE
  Predictors of clinical worsening in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy remain unknown. This study aims to identify demographic, clinical, and magnetic resonance imaging predictors of incident strokes, incident dementia, clinical deterioration, and death in patients with this genetically proven disease.
  
  
  METHODS
  Two hundred ninety subjects (mean age, 50.6±11.4 years) were assessed at baseline and followed up for 36 months. Incident clinical events were recorded, and clinical scores included the Mini Mental State Examination, Mattis Dementia Rating Scale, modified Rankin Scale, and Barthel index. The number of lacunes and microbleeds, the volume of white-matter hyperintensities, and brain parenchymal fraction were assessed on baseline magnetic resonance imaging. Data were analyzed by ANCOVA, multivariable logistic regression, and Cox proportional hazard models.
  
  
  RESULTS
  Incident stroke occurred in 55 of 278 patients (19.8%). Moderate or severe disability developed in 19 of 210 (9%) nondisabled individuals, incident dementia in 49 of 231 (20%) nondemented subjects, and 4.8% of patients died. Active smoking, the number of lacunes, and brain parenchymal fraction independently predicted incident stroke during follow-up. Gait disturbance, dementia, and brain parenchymal fraction predicted progression toward moderate or severe disability. Active smoking, disability, and brain parenchymal fraction predicted incident dementia. Age was the only significant predictor of death.
  
  
  CONCLUSIONS
  Clinical assessment and brain magnetic resonance imaging aid in predicting incident clinical events and clinical deterioration in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. There is a bidirectional relationship between dementia and moderate or severe disability in predicting each other's onset. Active smoking is a modifiable risk factor associated with clinical progression in Notch3 mutation carriers.
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Cité, Paris, France (H.C., D.H, O.G., E.J., N.A., S.R., A.J.); INSERM UMR 1161, Paris, France (H.C., D.H., E.J.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany (M.D., C.O., N.Z., M.D.); Department of Neuroradiology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France (J.-P.G.); Bioclinica Inc, Lyon, France (C.P.); Unité de Recherche Clinique, GH Saint Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris, Université Paris Denis Diderot, Paris, France (E.V.); and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M.D.). hugues.chabriat@lrb.aphp.fr.
authors.forename: Hugues
authors.initials: H
authors.lastname: Chabriat
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Cité, Paris, France (H.C., D.H, O.G., E.J., N.A., S.R., A.J.); INSERM UMR 1161, Paris, France (H.C., D.H., E.J.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany (M.D., C.O., N.Z., M.D.); Department of Neuroradiology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France (J.-P.G.); Bioclinica Inc, Lyon, France (C.P.); Unité de Recherche Clinique, GH Saint Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris, Université Paris Denis Diderot, Paris, France (E.V.); and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M.D.).
authors.forename: Dominique
authors.initials: D
authors.lastname: Hervé
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Cité, Paris, France (H.C., D.H, O.G., E.J., N.A., S.R., A.J.); INSERM UMR 1161, Paris, France (H.C., D.H., E.J.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany (M.D., C.O., N.Z., M.D.); Department of Neuroradiology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France (J.-P.G.); Bioclinica Inc, Lyon, France (C.P.); Unité de Recherche Clinique, GH Saint Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris, Université Paris Denis Diderot, Paris, France (E.V.); and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M.D.).
authors.forename: Marco
authors.initials: M
authors.lastname: Duering
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Cité, Paris, France (H.C., D.H, O.G., E.J., N.A., S.R., A.J.); INSERM UMR 1161, Paris, France (H.C., D.H., E.J.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany (M.D., C.O., N.Z., M.D.); Department of Neuroradiology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France (J.-P.G.); Bioclinica Inc, Lyon, France (C.P.); Unité de Recherche Clinique, GH Saint Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris, Université Paris Denis Diderot, Paris, France (E.V.); and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M.D.).
authors.forename: Ophelia
authors.initials: O
authors.lastname: Godin
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Cité, Paris, France (H.C., D.H, O.G., E.J., N.A., S.R., A.J.); INSERM UMR 1161, Paris, France (H.C., D.H., E.J.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany (M.D., C.O., N.Z., M.D.); Department of Neuroradiology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France (J.-P.G.); Bioclinica Inc, Lyon, France (C.P.); Unité de Recherche Clinique, GH Saint Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris, Université Paris Denis Diderot, Paris, France (E.V.); and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M.D.).
authors.forename: Eric
authors.initials: E
authors.lastname: Jouvent
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Cité, Paris, France (H.C., D.H, O.G., E.J., N.A., S.R., A.J.); INSERM UMR 1161, Paris, France (H.C., D.H., E.J.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany (M.D., C.O., N.Z., M.D.); Department of Neuroradiology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France (J.-P.G.); Bioclinica Inc, Lyon, France (C.P.); Unité de Recherche Clinique, GH Saint Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris, Université Paris Denis Diderot, Paris, France (E.V.); and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M.D.).
authors.forename: Christian
authors.initials: C
authors.lastname: Opherk
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Cité, Paris, France (H.C., D.H, O.G., E.J., N.A., S.R., A.J.); INSERM UMR 1161, Paris, France (H.C., D.H., E.J.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany (M.D., C.O., N.Z., M.D.); Department of Neuroradiology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France (J.-P.G.); Bioclinica Inc, Lyon, France (C.P.); Unité de Recherche Clinique, GH Saint Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris, Université Paris Denis Diderot, Paris, France (E.V.); and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M.D.).
authors.forename: Nassira
authors.initials: N
authors.lastname: Alili
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Cité, Paris, France (H.C., D.H, O.G., E.J., N.A., S.R., A.J.); INSERM UMR 1161, Paris, France (H.C., D.H., E.J.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany (M.D., C.O., N.Z., M.D.); Department of Neuroradiology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France (J.-P.G.); Bioclinica Inc, Lyon, France (C.P.); Unité de Recherche Clinique, GH Saint Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris, Université Paris Denis Diderot, Paris, France (E.V.); and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M.D.).
authors.forename: Sonia
authors.initials: S
authors.lastname: Reyes
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Cité, Paris, France (H.C., D.H, O.G., E.J., N.A., S.R., A.J.); INSERM UMR 1161, Paris, France (H.C., D.H., E.J.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany (M.D., C.O., N.Z., M.D.); Department of Neuroradiology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France (J.-P.G.); Bioclinica Inc, Lyon, France (C.P.); Unité de Recherche Clinique, GH Saint Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris, Université Paris Denis Diderot, Paris, France (E.V.); and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M.D.).
authors.forename: Aude
authors.initials: A
authors.lastname: Jabouley
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Cité, Paris, France (H.C., D.H, O.G., E.J., N.A., S.R., A.J.); INSERM UMR 1161, Paris, France (H.C., D.H., E.J.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany (M.D., C.O., N.Z., M.D.); Department of Neuroradiology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France (J.-P.G.); Bioclinica Inc, Lyon, France (C.P.); Unité de Recherche Clinique, GH Saint Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris, Université Paris Denis Diderot, Paris, France (E.V.); and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M.D.).
authors.forename: Nikola
authors.initials: N
authors.lastname: Zieren
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Cité, Paris, France (H.C., D.H, O.G., E.J., N.A., S.R., A.J.); INSERM UMR 1161, Paris, France (H.C., D.H., E.J.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany (M.D., C.O., N.Z., M.D.); Department of Neuroradiology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France (J.-P.G.); Bioclinica Inc, Lyon, France (C.P.); Unité de Recherche Clinique, GH Saint Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris, Université Paris Denis Diderot, Paris, France (E.V.); and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M.D.).
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Guichard
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Cité, Paris, France (H.C., D.H, O.G., E.J., N.A., S.R., A.J.); INSERM UMR 1161, Paris, France (H.C., D.H., E.J.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany (M.D., C.O., N.Z., M.D.); Department of Neuroradiology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France (J.-P.G.); Bioclinica Inc, Lyon, France (C.P.); Unité de Recherche Clinique, GH Saint Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris, Université Paris Denis Diderot, Paris, France (E.V.); and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M.D.).
authors.forename: Chahin
authors.initials: C
authors.lastname: Pachai
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Cité, Paris, France (H.C., D.H, O.G., E.J., N.A., S.R., A.J.); INSERM UMR 1161, Paris, France (H.C., D.H., E.J.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany (M.D., C.O., N.Z., M.D.); Department of Neuroradiology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France (J.-P.G.); Bioclinica Inc, Lyon, France (C.P.); Unité de Recherche Clinique, GH Saint Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris, Université Paris Denis Diderot, Paris, France (E.V.); and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M.D.).
authors.forename: Eric
authors.initials: E
authors.lastname: Vicaut
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Cité, Paris, France (H.C., D.H, O.G., E.J., N.A., S.R., A.J.); INSERM UMR 1161, Paris, France (H.C., D.H., E.J.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany (M.D., C.O., N.Z., M.D.); Department of Neuroradiology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France (J.-P.G.); Bioclinica Inc, Lyon, France (C.P.); Unité de Recherche Clinique, GH Saint Louis-Lariboisière, Assistance Publique des Hôpitaux de Paris, Université Paris Denis Diderot, Paris, France (E.V.); and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M.D.).
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
mesh_terms: D000328:Adult; D046589:CADASIL / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology*; D015331:Cohort Studies; D003704:Dementia / Q000175:diagnosis / Q000453:epidemiology / Q000523:psychology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000639:trends; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies
keywords: CADASIL; cerebral small vessel diseases; cohort studies; magnetic resonance imaging; risk factors