title: Microstructural white matter changes underlying cognitive and behavioural impairment in ALS--an in vivo study using DTI.
abstract: BACKGROUND
  A relevant fraction of patients with amyotrophic lateral sclerosis (ALS) exhibit a fronto-temporal pattern of cognitive and behavioural disturbances with pronounced deficits in executive functioning and cognitive control of behaviour. Structural imaging shows a decline in fronto-temporal brain areas, but most brain imaging studies did not evaluate cognitive status. We investigated microstructural white matter changes underlying cognitive impairment using diffusion tensor imaging (DTI) in a large cohort of ALS patients.
  
  
  METHODS
  We assessed 72 non-demented ALS patients and 65 matched healthy control subjects using a comprehensive neuropsychological test battery and DTI. We compared DTI measures of fiber tract integrity using tract-based spatial statistics among ALS patients with and without cognitive impairment and healthy controls. Neuropsychological performance and behavioural measures were correlated with DTI measures.
  
  
  RESULTS
  Patients without cognitive impairment demonstrated white matter changes predominantly in motor tracts, including the corticospinal tract and the body of corpus callosum. Those with impairments (ca. 30%) additionally presented significant white matter alterations in extra-motor regions, particularly the frontal lobe. Executive and memory performance and behavioural measures were correlated with fiber tract integrity in large association tracts.
  
  
  CONCLUSIONS
  In non-demented cognitively impaired ALS patients, white matter changes measured by DTI are related to disturbances of executive and memory functions, including prefrontal and temporal regions. In a group comparison, DTI is able to observe differences between cognitively unimpaired and impaired ALS patients.
authors.affiliation: Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kasper
authors.affiliation: DZNE German Centre for Neurodegenerative Diseases, Site Rostock, Rostock, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Schuster
authors.affiliation: DZNE German Centre for Neurodegenerative Diseases, Site Magdeburg, Magdeburg, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Machts
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Joern
authors.initials: J
authors.lastname: Kaufmann
authors.affiliation: Department of Neurology, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bittner
authors.affiliation: DZNE German Centre for Neurodegenerative Diseases, Site Magdeburg, Magdeburg, Germany; Department of Neurology, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Vielhaber
authors.affiliation: Department of Neurology, University of Rostock, Rostock, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Benecke
authors.affiliation: Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany; DZNE German Centre for Neurodegenerative Diseases, Site Rostock, Rostock, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Teipel
authors.affiliation: DZNE German Centre for Neurodegenerative Diseases, Site Rostock, Rostock, Germany; Department of Neurology, University of Rostock, Rostock, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Prudlo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology* / Q000503:physiopathology*; D001519:Behavior / Q000502:physiology*; D003071:Cognition; D015331:Cohort Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D066127:White Matter / Q000473:pathology* / Q000503:physiopathology