title: Cognitive impairment in myotonic dystrophy type 1 is associated with white matter damage.
abstract: OBJECTIVE
  To investigate grey (GM) and white matter (WM) abnormalities and their effects on cognitive and behavioral deficits in a large, phenotypically and genotypically well-characterized cohort of classic adult (aDM1, age at onset ≥ 20 years) or juvenile (jDM1, age at onset <20 years) patients with myotonic dystrophy type 1 (DM1).
  
  
  METHODS
  A case-control study including 51 DM1 patients (17 jDM1 and 34 aDM1) and 34 controls was conducted at an academic medical center. Clinical, cognitive and structural MRI evaluations were obtained. Quantitative assessments of regional GM volumes, WM hyperintensities (WMHs), and microstructural WM tract damage were performed. The association between structural brain damage and clinical and cognitive findings was assessed.
  
  
  RESULTS
  DM1 patients showed a high prevalence of WMHs, severe regional GM atrophy including the key nodes of the sensorimotor and main cognitive brain networks, and WM microstructural damage of the interhemispheric, corticospinal, limbic and associative pathways. WM tract damage extends well beyond the focal WMHs. While aDM1 patients had severe patterns of GM atrophy and WM tract damage, in jDM1 patients WM abnormalities exceeded GM involvement. In DM1, WMHs and microstructural damage, but not GM atrophy, correlated with cognitive deficits.
  
  
  CONCLUSIONS
  WM damage, through a disconnection between GM structures, is likely to be the major contributor to cognitive impairment in DM1. Our MRI findings in aDM1 and jDM1 patients support the hypothesis of a degenerative (premature aging) origin of the GM abnormalities and of developmental changes as the principal substrates of microstructural WM alterations in DM1.
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: Francesca
authors.initials: F
authors.lastname: Caso
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: Federica
authors.initials: F
authors.lastname: Agosta
authors.affiliation: Neurology Clinic, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Stojan
authors.initials: S
authors.lastname: Peric
authors.affiliation: Neurology Clinic, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Vidosava
authors.initials: V
authors.lastname: Rakočević-Stojanović
authors.affiliation: Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, Foggia, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.affiliation: Neurology Clinic, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Kostic
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: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009223:Myotonic Dystrophy / Q000150:complications* / Q000175:diagnosis / Q000473:pathology*; D009483:Neuropsychological Tests; D066127:White Matter / Q000473:pathology*; D055815:Young Adult