title: Predictors and Clinical Impact of Incident Lacunes in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.
abstract: Previous studies in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy showed that accumulation of lacunes strongly relate to clinical severity. However, the potential predictors of incident lacunes and their clinical consequences over a short time frame have not been investigated. This study aimed to determine the predictors and clinical impact of such lesions in a large cohort of patients.
  
  
  
  Two hundred and six NOTCH3 mutation carriers (mean age, 49.5±10.6 years) were followed up over 3 years. Incident lacunes were identified using difference imaging from 3-dimensional T1 images. Clinical events and change in different clinical scores such as the Mattis Dementia Rating Scale, Modified Rankin Scale, Barthel index, and time to complete part A and part B of Trail Making Test were recorded. Associations were analyzed with multivariable logistic regression analysis and ANCOVA.
  
  
  
  Over a mean period of 3.4±0.7 years, incident lacunes occurred in 51 of 206 patients. Both the number of lacunes (P<0.0001) and systolic blood pressure at baseline (P<0.01) were independent predictors of incident lacunes during follow-up. The results were still significant after excluding patients with systolic blood pressure >140 mm Hg. Incident lacunes were also associated with incident stroke and with change in time to complete Trail Making Test part B, initiation/perseveration subscale of the Mattis Dementia Rating Scale and Barthel Index over the study period.
  
  
  
  Systolic blood pressure and the number of prevalent lacunes are independent predictors of incident lacunes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. These lesions mainly impact executive performances and functional independence over 3 years.
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hoôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Citeé, Paris, France (F.D.G., E.J., D.H., O.G., H.C.); INSERM UMR 1161, Paris, France (Y.L., F.D.G., E.J., D.H., H.C.); Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China (Y.L.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University LMU, Munich, Germany (M. Duering, M. Dichgans); Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M. Dichgans); and German Center for Neurodegenerative Diseases (DZNE), Munich (M. Dichgans).
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Ling
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hoôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Citeé, Paris, France (F.D.G., E.J., D.H., O.G., H.C.); INSERM UMR 1161, Paris, France (Y.L., F.D.G., E.J., D.H., H.C.); Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China (Y.L.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University LMU, Munich, Germany (M. Duering, M. Dichgans); Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M. Dichgans); and German Center for Neurodegenerative Diseases (DZNE), Munich (M. Dichgans).
authors.forename: François
authors.initials: F
authors.lastname: De Guio
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hoôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Citeé, Paris, France (F.D.G., E.J., D.H., O.G., H.C.); INSERM UMR 1161, Paris, France (Y.L., F.D.G., E.J., D.H., H.C.); Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China (Y.L.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University LMU, Munich, Germany (M. Duering, M. Dichgans); Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M. Dichgans); and German Center for Neurodegenerative Diseases (DZNE), Munich (M. Dichgans).
authors.forename: Marco
authors.initials: M
authors.lastname: Duering
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hoôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Citeé, Paris, France (F.D.G., E.J., D.H., O.G., H.C.); INSERM UMR 1161, Paris, France (Y.L., F.D.G., E.J., D.H., H.C.); Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China (Y.L.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University LMU, Munich, Germany (M. Duering, M. Dichgans); Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M. Dichgans); and German Center for Neurodegenerative Diseases (DZNE), Munich (M. Dichgans).
authors.forename: Eric
authors.initials: E
authors.lastname: Jouvent
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hoôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Citeé, Paris, France (F.D.G., E.J., D.H., O.G., H.C.); INSERM UMR 1161, Paris, France (Y.L., F.D.G., E.J., D.H., H.C.); Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China (Y.L.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University LMU, Munich, Germany (M. Duering, M. Dichgans); Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M. Dichgans); and German Center for Neurodegenerative Diseases (DZNE), Munich (M. Dichgans).
authors.forename: Dominique
authors.initials: D
authors.lastname: Hervé
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hoôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Citeé, Paris, France (F.D.G., E.J., D.H., O.G., H.C.); INSERM UMR 1161, Paris, France (Y.L., F.D.G., E.J., D.H., H.C.); Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China (Y.L.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University LMU, Munich, Germany (M. Duering, M. Dichgans); Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M. Dichgans); and German Center for Neurodegenerative Diseases (DZNE), Munich (M. Dichgans).
authors.forename: Ophélia
authors.initials: O
authors.lastname: Godin
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hoôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Citeé, Paris, France (F.D.G., E.J., D.H., O.G., H.C.); INSERM UMR 1161, Paris, France (Y.L., F.D.G., E.J., D.H., H.C.); Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China (Y.L.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University LMU, Munich, Germany (M. Duering, M. Dichgans); Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M. Dichgans); and German Center for Neurodegenerative Diseases (DZNE), Munich (M. Dichgans).
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
authors.affiliation: From the Department of Neurology, GH Saint-Louis-Lariboisière, Assistance Publique des Hoôpitaux de Paris (APHP), Université Paris Denis Diderot and DHU NeuroVasc Sorbonne Paris-Citeé, Paris, France (F.D.G., E.J., D.H., O.G., H.C.); INSERM UMR 1161, Paris, France (Y.L., F.D.G., E.J., D.H., H.C.); Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China (Y.L.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University LMU, Munich, Germany (M. Duering, M. Dichgans); Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M. Dichgans); and German Center for Neurodegenerative Diseases (DZNE), Munich (M. Dichgans). hugues.chabriat@lrb.aphp.fr.
authors.forename: Hugues
authors.initials: H
authors.lastname: Chabriat
mesh_terms: D000328:Adult; D046589:CADASIL / Q000000981:diagnostic imaging* / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D059409:Stroke, Lacunar / Q000000981:diagnostic imaging* / Q000453:epidemiology*
keywords: CADASIL; cerebral small vessel disease; magnetic resonance imaging; risk factor; stroke