title: Structural Brain Connectome and Cognitive Impairment in Parkinson Disease.
abstract: Purpose To investigate the structural brain connectome in patients with Parkinson disease (PD) and mild cognitive impairment (MCI) and in patients with PD without MCI. Materials and Methods This prospective study was approved by the local ethics committees, and written informed consent was obtained from all subjects prior to enrollment. The individual structural brain connectome of 170 patients with PD (54 with MCI, 116 without MCI) and 41 healthy control subjects was obtained by using deterministic diffusion-tensor tractography. A network-based statistic was used to assess structural connectivity differences among groups. Results Patients with PD and MCI had global network alterations when compared with both control subjects and patients with PD without MCI (range, P = .004 to P = .048). Relative to control subjects, patients with PD and MCI had a large basal ganglia and frontoparietal network with decreased fractional anisotropy (FA) in the right hemisphere and a subnetwork with increased mean diffusivity (MD) involving similar regions bilaterally (P < .01). When compared with patients with PD without MCI, those with PD and MCI had a network with decreased FA, including basal ganglia and frontotemporoparietal regions bilaterally (P < .05). Similar findings were obtained by adjusting for motor disability (P < .05, permutation-corrected P = .06). At P < .01, patients with PD and MCI did not show network alterations relative to patients with PD without MCI. Network FA and MD values were used to differentiate patients with PD and MCI from healthy control subjects and patients with PD without MCI with fair to good accuracy (cross-validated area under the receiver operating characteristic curve [principal + secondary connected components] range, 0.75-0.85). Conclusion A disruption of structural connections between brain areas forming a network contributes to determine an altered information integration and organization and thus cognitive deficits in patients with PD. These results provide novel information concerning the structural substrates of MCI in patients with PD and may offer markers that can be used to differentiate between patients with PD and MCI and patients with PD without MCI.©RSNA, 2016 Online supplemental material is available for this article.
authors.affiliation: From the Neuroimaging Research Unit (S.G., F.A., S.B., E.C., D.G., M.F.) and Department of Neurology (M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia (E.S., T.S., I.S., V.S., V.S.K.); Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands (M.P.v.d.H.); and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Galantucci
authors.affiliation: From the Neuroimaging Research Unit (S.G., F.A., S.B., E.C., D.G., M.F.) and Department of Neurology (M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia (E.S., T.S., I.S., V.S., V.S.K.); Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands (M.P.v.d.H.); and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
authors.forename: Federica
authors.initials: F
authors.lastname: Agosta
authors.affiliation: From the Neuroimaging Research Unit (S.G., F.A., S.B., E.C., D.G., M.F.) and Department of Neurology (M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia (E.S., T.S., I.S., V.S., V.S.K.); Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands (M.P.v.d.H.); and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
authors.forename: Elka
authors.initials: E
authors.lastname: Stefanova
authors.affiliation: From the Neuroimaging Research Unit (S.G., F.A., S.B., E.C., D.G., M.F.) and Department of Neurology (M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia (E.S., T.S., I.S., V.S., V.S.K.); Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands (M.P.v.d.H.); and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
authors.forename: Silvia
authors.initials: S
authors.lastname: Basaia
authors.affiliation: From the Neuroimaging Research Unit (S.G., F.A., S.B., E.C., D.G., M.F.) and Department of Neurology (M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia (E.S., T.S., I.S., V.S., V.S.K.); Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands (M.P.v.d.H.); and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
authors.forename: Martijn P
authors.initials: MP
authors.lastname: van den Heuvel
authors.affiliation: From the Neuroimaging Research Unit (S.G., F.A., S.B., E.C., D.G., M.F.) and Department of Neurology (M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia (E.S., T.S., I.S., V.S., V.S.K.); Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands (M.P.v.d.H.); and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
authors.forename: Tanja
authors.initials: T
authors.lastname: Stojković
authors.affiliation: From the Neuroimaging Research Unit (S.G., F.A., S.B., E.C., D.G., M.F.) and Department of Neurology (M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia (E.S., T.S., I.S., V.S., V.S.K.); Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands (M.P.v.d.H.); and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
authors.forename: Elisa
authors.initials: E
authors.lastname: Canu
authors.affiliation: From the Neuroimaging Research Unit (S.G., F.A., S.B., E.C., D.G., M.F.) and Department of Neurology (M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia (E.S., T.S., I.S., V.S., V.S.K.); Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands (M.P.v.d.H.); and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
authors.forename: Iva
authors.initials: I
authors.lastname: Stanković
authors.affiliation: From the Neuroimaging Research Unit (S.G., F.A., S.B., E.C., D.G., M.F.) and Department of Neurology (M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia (E.S., T.S., I.S., V.S., V.S.K.); Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands (M.P.v.d.H.); and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
authors.forename: Vladana
authors.initials: V
authors.lastname: Spica
authors.affiliation: From the Neuroimaging Research Unit (S.G., F.A., S.B., E.C., D.G., M.F.) and Department of Neurology (M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia (E.S., T.S., I.S., V.S., V.S.K.); Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands (M.P.v.d.H.); and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.affiliation: From the Neuroimaging Research Unit (S.G., F.A., S.B., E.C., D.G., M.F.) and Department of Neurology (M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia (E.S., T.S., I.S., V.S., V.S.K.); Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands (M.P.v.d.H.); and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
authors.forename: Delia
authors.initials: D
authors.lastname: Gagliardi
authors.affiliation: From the Neuroimaging Research Unit (S.G., F.A., S.B., E.C., D.G., M.F.) and Department of Neurology (M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia (E.S., T.S., I.S., V.S., V.S.K.); Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands (M.P.v.d.H.); and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Kostić
authors.affiliation: From the Neuroimaging Research Unit (S.G., F.A., S.B., E.C., D.G., M.F.) and Department of Neurology (M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia (E.S., T.S., I.S., V.S., V.S.K.); Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands (M.P.v.d.H.); and Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.).
authors.forename: Massimo
authors.identifier: 0000-0002-5485-0479
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology*; D063132:Connectome / Q000379:methods*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000473:pathology; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology*