Prediction of 3-year clinical course in CADASIL.
OBJECTIVE
To obtain simple models predicting disease evolution at 3 years for a given patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).


METHODS
Based on data obtained in a prospective study of 236 patients, we built and validated models predicting, at the individual level, 3-year changes in Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale (MDRS), Trail Making Test version B (TMTB), and modified Rankin Scale (mRS). These models were based on different sets of predictors obtained at baseline, including either clinical data (epidemiologic data and cardiovascular risk factors) or clinical data and quantitative MRI markers (volume of lacunes [LLV], volume of white matter hyperintensities, normalized brain volume [BPF], number of microbleeds). The Bayesian information criterion (BIC) and the coefficient of determination (R2) were used to determine models with the highest predictive ability and the lowest numbers of predictors.


RESULTS
We obtained validated models with a demonstrated ability to predict, for a given patient, 3-year changes in MMSE, MDRS, TMTB, and mRS (R2on independent samples: 0.22, 0.12, 0.09, and 0.17, respectively). In all cases, the best models according to R2and BIC values included only the baseline values of the outcome, of BPF, and of LLV. Inclusion of other potential predictors always led to a loss of generalizability.


CONCLUSIONS
The prediction of 3-year changes in MMSE, MDRS, TMTB, and mRS for a given patient with CADASIL can be obtained using simple models relying only on the initial values of the considered score, BPF, and LLV.
From UMR-S 1161 INSERM (E.J., F.D.G., D.H., H.C.), Sorbonne Paris Cité, University Paris Diderot; Department of Neurology (E.J., F.D.G., D.H., H.C.), AP-HP, Lariboisière Hospital, Paris; DHU NeuroVasc Sorbonne Paris Cité (E.J., F.D.G., D.H., H.C.); LNAO (E.D., F.H.-S., J.-F.M.), Neurospin, I2BM, CEA, Saclay, France; Institute for Stroke and Dementia Research, Klinikum der Universität München (M. Duering, M. Dichgans), Munich; Munich Cluster for Systems Neurology (SyNergy) (M. Dichgans), Munich; German Center for Neurodegenerative Diseases (DZNE) (M. Dichgans), Munich, Germany; and Department of Neurology (S.R., R.S.), Medical University of Graz, Austria.
Eric
E
Jouvent
From UMR-S 1161 INSERM (E.J., F.D.G., D.H., H.C.), Sorbonne Paris Cité, University Paris Diderot; Department of Neurology (E.J., F.D.G., D.H., H.C.), AP-HP, Lariboisière Hospital, Paris; DHU NeuroVasc Sorbonne Paris Cité (E.J., F.D.G., D.H., H.C.); LNAO (E.D., F.H.-S., J.-F.M.), Neurospin, I2BM, CEA, Saclay, France; Institute for Stroke and Dementia Research, Klinikum der Universität München (M. Duering, M. Dichgans), Munich; Munich Cluster for Systems Neurology (SyNergy) (M. Dichgans), Munich; German Center for Neurodegenerative Diseases (DZNE) (M. Dichgans), Munich, Germany; and Department of Neurology (S.R., R.S.), Medical University of Graz, Austria.
Edouard
E
Duchesnay
From UMR-S 1161 INSERM (E.J., F.D.G., D.H., H.C.), Sorbonne Paris Cité, University Paris Diderot; Department of Neurology (E.J., F.D.G., D.H., H.C.), AP-HP, Lariboisière Hospital, Paris; DHU NeuroVasc Sorbonne Paris Cité (E.J., F.D.G., D.H., H.C.); LNAO (E.D., F.H.-S., J.-F.M.), Neurospin, I2BM, CEA, Saclay, France; Institute for Stroke and Dementia Research, Klinikum der Universität München (M. Duering, M. Dichgans), Munich; Munich Cluster for Systems Neurology (SyNergy) (M. Dichgans), Munich; German Center for Neurodegenerative Diseases (DZNE) (M. Dichgans), Munich, Germany; and Department of Neurology (S.R., R.S.), Medical University of Graz, Austria.
Foued
F
Hadj-Selem
From UMR-S 1161 INSERM (E.J., F.D.G., D.H., H.C.), Sorbonne Paris Cité, University Paris Diderot; Department of Neurology (E.J., F.D.G., D.H., H.C.), AP-HP, Lariboisière Hospital, Paris; DHU NeuroVasc Sorbonne Paris Cité (E.J., F.D.G., D.H., H.C.); LNAO (E.D., F.H.-S., J.-F.M.), Neurospin, I2BM, CEA, Saclay, France; Institute for Stroke and Dementia Research, Klinikum der Universität München (M. Duering, M. Dichgans), Munich; Munich Cluster for Systems Neurology (SyNergy) (M. Dichgans), Munich; German Center for Neurodegenerative Diseases (DZNE) (M. Dichgans), Munich, Germany; and Department of Neurology (S.R., R.S.), Medical University of Graz, Austria.
François
F
De Guio
From UMR-S 1161 INSERM (E.J., F.D.G., D.H., H.C.), Sorbonne Paris Cité, University Paris Diderot; Department of Neurology (E.J., F.D.G., D.H., H.C.), AP-HP, Lariboisière Hospital, Paris; DHU NeuroVasc Sorbonne Paris Cité (E.J., F.D.G., D.H., H.C.); LNAO (E.D., F.H.-S., J.-F.M.), Neurospin, I2BM, CEA, Saclay, France; Institute for Stroke and Dementia Research, Klinikum der Universität München (M. Duering, M. Dichgans), Munich; Munich Cluster for Systems Neurology (SyNergy) (M. Dichgans), Munich; German Center for Neurodegenerative Diseases (DZNE) (M. Dichgans), Munich, Germany; and Department of Neurology (S.R., R.S.), Medical University of Graz, Austria.
Jean-François
JF
Mangin
From UMR-S 1161 INSERM (E.J., F.D.G., D.H., H.C.), Sorbonne Paris Cité, University Paris Diderot; Department of Neurology (E.J., F.D.G., D.H., H.C.), AP-HP, Lariboisière Hospital, Paris; DHU NeuroVasc Sorbonne Paris Cité (E.J., F.D.G., D.H., H.C.); LNAO (E.D., F.H.-S., J.-F.M.), Neurospin, I2BM, CEA, Saclay, France; Institute for Stroke and Dementia Research, Klinikum der Universität München (M. Duering, M. Dichgans), Munich; Munich Cluster for Systems Neurology (SyNergy) (M. Dichgans), Munich; German Center for Neurodegenerative Diseases (DZNE) (M. Dichgans), Munich, Germany; and Department of Neurology (S.R., R.S.), Medical University of Graz, Austria.
Dominique
D
Hervé
From UMR-S 1161 INSERM (E.J., F.D.G., D.H., H.C.), Sorbonne Paris Cité, University Paris Diderot; Department of Neurology (E.J., F.D.G., D.H., H.C.), AP-HP, Lariboisière Hospital, Paris; DHU NeuroVasc Sorbonne Paris Cité (E.J., F.D.G., D.H., H.C.); LNAO (E.D., F.H.-S., J.-F.M.), Neurospin, I2BM, CEA, Saclay, France; Institute for Stroke and Dementia Research, Klinikum der Universität München (M. Duering, M. Dichgans), Munich; Munich Cluster for Systems Neurology (SyNergy) (M. Dichgans), Munich; German Center for Neurodegenerative Diseases (DZNE) (M. Dichgans), Munich, Germany; and Department of Neurology (S.R., R.S.), Medical University of Graz, Austria.
Marco
M
Duering
From UMR-S 1161 INSERM (E.J., F.D.G., D.H., H.C.), Sorbonne Paris Cité, University Paris Diderot; Department of Neurology (E.J., F.D.G., D.H., H.C.), AP-HP, Lariboisière Hospital, Paris; DHU NeuroVasc Sorbonne Paris Cité (E.J., F.D.G., D.H., H.C.); LNAO (E.D., F.H.-S., J.-F.M.), Neurospin, I2BM, CEA, Saclay, France; Institute for Stroke and Dementia Research, Klinikum der Universität München (M. Duering, M. Dichgans), Munich; Munich Cluster for Systems Neurology (SyNergy) (M. Dichgans), Munich; German Center for Neurodegenerative Diseases (DZNE) (M. Dichgans), Munich, Germany; and Department of Neurology (S.R., R.S.), Medical University of Graz, Austria.
Stefan
S
Ropele
From UMR-S 1161 INSERM (E.J., F.D.G., D.H., H.C.), Sorbonne Paris Cité, University Paris Diderot; Department of Neurology (E.J., F.D.G., D.H., H.C.), AP-HP, Lariboisière Hospital, Paris; DHU NeuroVasc Sorbonne Paris Cité (E.J., F.D.G., D.H., H.C.); LNAO (E.D., F.H.-S., J.-F.M.), Neurospin, I2BM, CEA, Saclay, France; Institute for Stroke and Dementia Research, Klinikum der Universität München (M. Duering, M. Dichgans), Munich; Munich Cluster for Systems Neurology (SyNergy) (M. Dichgans), Munich; German Center for Neurodegenerative Diseases (DZNE) (M. Dichgans), Munich, Germany; and Department of Neurology (S.R., R.S.), Medical University of Graz, Austria.
Reinhold
R
Schmidt
From UMR-S 1161 INSERM (E.J., F.D.G., D.H., H.C.), Sorbonne Paris Cité, University Paris Diderot; Department of Neurology (E.J., F.D.G., D.H., H.C.), AP-HP, Lariboisière Hospital, Paris; DHU NeuroVasc Sorbonne Paris Cité (E.J., F.D.G., D.H., H.C.); LNAO (E.D., F.H.-S., J.-F.M.), Neurospin, I2BM, CEA, Saclay, France; Institute for Stroke and Dementia Research, Klinikum der Universität München (M. Duering, M. Dichgans), Munich; Munich Cluster for Systems Neurology (SyNergy) (M. Dichgans), Munich; German Center for Neurodegenerative Diseases (DZNE) (M. Dichgans), Munich, Germany; and Department of Neurology (S.R., R.S.), Medical University of Graz, Austria.
Martin
M
Dichgans
From UMR-S 1161 INSERM (E.J., F.D.G., D.H., H.C.), Sorbonne Paris Cité, University Paris Diderot; Department of Neurology (E.J., F.D.G., D.H., H.C.), AP-HP, Lariboisière Hospital, Paris; DHU NeuroVasc Sorbonne Paris Cité (E.J., F.D.G., D.H., H.C.); LNAO (E.D., F.H.-S., J.-F.M.), Neurospin, I2BM, CEA, Saclay, France; Institute for Stroke and Dementia Research, Klinikum der Universität München (M. Duering, M. Dichgans), Munich; Munich Cluster for Systems Neurology (SyNergy) (M. Dichgans), Munich; German Center for Neurodegenerative Diseases (DZNE) (M. Dichgans), Munich, Germany; and Department of Neurology (S.R., R.S.), Medical University of Graz, Austria. hugues.chabriat@aphp.fr.
Hugues
H
Chabriat
D000328:Adult; D000368:Aged; D001499:Bayes Theorem; D046589:CADASIL / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D005602:France; D005858:Germany; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012720:Severity of Illness Index; D055815:Young Adult
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