title: Cortical atrophy in ALS is critically associated with neuropsychiatric and cognitive changes.
abstract: OBJECTIVE
  To characterize the patterns of brain atrophy in patients with amyotrophic lateral sclerosis (ALS) with and without cognitive and neuropsychiatric symptoms, in comparison to controls and patients with ALS-frontotemporal dementia (FTD).
  
  
  METHODS
  A total of 57 participants (ALS = 22; ALS-FTD = 17; controls = 18) were included, following current ALS and FTD criteria. Patients with ALS were further subclassified into ALS with cognitive and behavioral symptoms (ALS-plus; n = 8) and those without (ALS; n = 14). By definition, ALS-plus did not reach the diagnostic threshold for ALS-FTD. All patients underwent neuropsychological and neuropsychiatric assessments, and underwent a brain MRI. Voxel-based morphometry analysis was conducted to establish patterns of brain atrophy.
  
  
  RESULTS
  Cortical atrophy in ALS was linked to neuropsychiatric and cognitive changes (ALS-plus vs ALS). Patients with ALS-plus had significant atrophy across motor and somatosensory as well as adjacent frontal and parietal areas, even after strict multiple comparison correction. By contrast, patients with ALS showed no significant cortical atrophy, and only brainstem atrophy. Importantly, atrophy in ALS-plus was not as widespread as in ALS-FTD, with ALS-plus atrophy mostly confined to motor and somatosensory areas, while atrophy in ALS-FTD also included substantial frontal and temporal atrophy.
  
  
  CONCLUSIONS
  The present findings establish that cortical atrophy in ALS is highly dependent upon neuropsychiatric and cognitive changes. Previous inconsistent findings of cortical atrophy in ALS likely relate to the inclusion of cognitively affected patients and patients with pure motor ALS.
authors: Neuroscience Research Australia, Sydney, Australia.
authors: Eneida
authors: E
authors: Mioshi
authors: Patricia
authors: P
authors: Lillo
authors: Belinda
authors: B
authors: Yew
authors: Sharpley
authors: S
authors: Hsieh
authors: Sharon
authors: S
authors: Savage
authors: John R
authors: JR
authors: Hodges
authors: Matthew C
authors: MC
authors: Kiernan
authors: Michael
authors: M
authors: Hornberger
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000473:pathology*; D001284:Atrophy / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology*; D003072:Cognition Disorders / Q000453:epidemiology / Q000473:pathology*; D005260:Female; D057180:Frontotemporal Dementia / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged