title: Structural MRI correlates of cognitive impairment in patients with multiple sclerosis: A Multicenter Study.
abstract: In a multicenter setting, we applied voxel-based methods to different structural MR imaging modalities to define the relative contributions of focal lesions, normal-appearing white matter (NAWM), and gray matter (GM) damage and their regional distribution to cognitive deficits as well as impairment of specific cognitive domains in multiple sclerosis (MS) patients. Approval of the institutional review boards was obtained, together with written informed consent from all participants. Standardized neuropsychological assessment and conventional, diffusion tensor and volumetric brain MRI sequences were collected from 61 relapsing-remitting MS patients and 61 healthy controls (HC) from seven centers. Patients with ≥2 abnormal tests were considered cognitively impaired (CI). The distribution of focal lesions, GM and WM atrophy, and microstructural WM damage were assessed using voxel-wise approaches. A random forest analysis identified the best imaging predictors of global cognitive impairment and deficits of specific cognitive domains. Twenty-three (38%) MS patients were CI. Compared with cognitively preserved (CP), CI MS patients had GM atrophy of the left thalamus, right hippocampus and parietal regions. They also showed atrophy of several WM tracts, mainly located in posterior brain regions and widespread WM diffusivity abnormalities. WM diffusivity abnormalities in cognitive-relevant WM tracts followed by atrophy of cognitive-relevant GM regions explained global cognitive impairment. Variable patterns of NAWM and GM damage were associated with deficits in selected cognitive domains. Structural, multiparametric, voxel-wise MRI approaches are feasible in a multicenter setting. The combination of different imaging modalities is needed to assess and monitor cognitive impairment in MS.
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.|Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Preziosa
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.|Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rocca
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pagani
authors.affiliation: Department of Neurological and Behavioral Sciences, University of Siena, Siena, Italy.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Stromillo
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Enzinger
authors.affiliation: MRI Center "SUN-FISM," Second University of Naples and Institute of Diagnosis and Care "Hermitage-Capodimonte,", Naples, Italy.|Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, I Division of Neurology, Second University of Naples, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gallo
authors.affiliation: Department of Radiology and Nuclear Medicine, MS Centre Amsterdam, VU Medical Centre, Amsterdam, Netherlands.
authors.forename: Hanneke E
authors.initials: HE
authors.lastname: Hulst
authors.affiliation: NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, United Kingdom.
authors.forename: Matteo
authors.initials: M
authors.lastname: Atzori
authors.affiliation: Unitat De Neuroimmunologia Clinica, CEM-Cat, Hospital Universitari Vall D'Hebron, Barcelona, Spain.
authors.forename: Deborah
authors.initials: D
authors.lastname: Pareto
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Gianna C
authors.initials: GC
authors.lastname: Riccitelli
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.affiliation: Department of Neurological and Behavioral Sciences, University of Siena, Siena, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: De Stefano
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Fazekas
authors.affiliation: MRI Center "SUN-FISM," Second University of Naples and Institute of Diagnosis and Care "Hermitage-Capodimonte,", Naples, Italy.|Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, I Division of Neurology, Second University of Naples, Naples, Italy.
authors.forename: Alvino
authors.initials: A
authors.lastname: Bisecco
authors.affiliation: Department of Radiology and Nuclear Medicine, MS Centre Amsterdam, VU Medical Centre, Amsterdam, Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, United Kingdom.
authors.forename: Tarek A
authors.initials: TA
authors.lastname: Yousry
authors.affiliation: Unitat De Neuroimmunologia Clinica, CEM-Cat, Hospital Universitari Vall D'Hebron, Barcelona, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Arévalo
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.|Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging* / Q000523:psychology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000523:psychology*; D009483:Neuropsychological Tests
keywords: atrophy; cognitive impairment; diffusion tensor MRI; multicenter; multiple sclerosis; voxel-wise analysis
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