title: Cognitive changes predict functional decline in ALS: a population-based longitudinal study.
abstract: OBJECTIVE
  To determine whether cognitive status in patients with amyotrophic lateral sclerosis (ALS) is a useful predictor of attrition and motor and cognitive decline.
  
  
  METHODS
  Cognitive testing was undertaken in a large population-based cohort of incident ALS patients using a longitudinal, case-control study design. Normative data for neuropsychological tests were generated using age-, sex-, and education-matched healthy controls who also underwent repeated assessments. Data were analyzed to generate models for progression/spread.
  
  
  RESULTS
  One hundred eighty-six patients with ALS who had no evidence of C9orf72 hexanucleotide repeat expansion were enrolled. A second and third assessment were undertaken in 98 and 46 of the patients with ALS, respectively. Executive impairment at the initial visit was associated with significantly higher rates of attrition due to disability or death and faster rates of motor functional decline, particularly decline in bulbar function. Decline in cognitive function was faster in patients who were cognitively impaired at baseline. Normal cognition at baseline was associated with tendency to remain cognitively intact, and with slower motor and cognitive progression.
  
  
  CONCLUSIONS
  Non-C9orf72-associated ALS is characterized by nonoverlapping cognitive subgroups with different disease trajectories. These findings have important implications for models of ALS pathogenesis, and for future clinical trial design.
authors.affiliation: Trinity College Institute of Neuroscience, Trinity College Dublin, Ireland. marwaelamin08@gmail.com
authors.forename: Marwa
authors.initials: M
authors.lastname: Elamin
authors.forename: Peter
authors.initials: P
authors.lastname: Bede
authors.forename: Susan
authors.initials: S
authors.lastname: Byrne
authors.forename: Norah
authors.initials: N
authors.lastname: Jordan
authors.forename: Laura
authors.initials: L
authors.lastname: Gallagher
authors.forename: Brona
authors.initials: B
authors.lastname: Wynne
authors.forename: Caoimhe
authors.initials: C
authors.lastname: O'Brien
authors.forename: Julie
authors.initials: J
authors.lastname: Phukan
authors.forename: Catherine
authors.initials: C
authors.lastname: Lynch
authors.forename: Niall
authors.initials: N
authors.lastname: Pender
authors.forename: Orla
authors.initials: O
authors.lastname: Hardiman
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D003071:Cognition; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests