title: Absence of practice effects in preclinical Alzheimer's disease.
abstract: OBJECTIVE
  To describe how practice effects influence cognitive trajectories and determine if a reduction in practice effects is a potential marker of Stage-III preclinical Alzheimer's disease (AD).
  
  
  METHODS
  Participants included 263 older adults who were cognitively normal at baseline (i.e., had a Clinical Dementia Rating [CDR] of 0; Morris, 1993) and returned for an average of 9.5 annual visits. Participants completed standard tests of episodic memory, visuospatial ability, semantic memory, and executive function. Progressors (n = 66) converted to CDR > 0 with a diagnosis of symptomatic AD after a minimum of 3 visits and stable participants (n = 197) never progressed to CDR > 0. Practice effects, defined as the slope of performance across Visits 1-3, were compared between groups and used within subjects to predict risk of conversion. Change-point models that accounted for retest were contrasted with linear models that ignored retest.
  
  
  RESULTS
  The stable group showed practice effects on episodic-memory measures (β = 0.14, SE = .02, p < .0001) but the progressor group did not (β = 0.03, SE = .03, p = .343). Across all participants, practice effects on episodic-memory tests were associated with a decreased risk of progression to AD as indicated by the subdistribution hazards model (SHR; Fine & Gray, 1999); SHR = .110, 95% CI [.032, .384], p = .001). Finally, use of change-point models dramatically altered rate-of-change estimates compared with models that ignored practice.
  
  
  CONCLUSIONS
  Our results indicate that preclinical AD is marked by a reduction in practice effects in episodic memory and that the magnitude of gain from retesting is inversely related to progression risk. Assessment of practice effects may be a face-valid indicator of Stage-III preclinical AD.
authors.affiliation: Department of Neurology, Washington University School of Medicine in St. Louis.
authors.forename: Jason
authors.initials: J
authors.lastname: Hassenstab
authors.affiliation: Department of Neurology, Washington University School of Medicine in St. Louis.
authors.forename: David
authors.initials: D
authors.lastname: Ruvolo
authors.affiliation: Division of Biostatistics, Washington University School of Medicine in St. Louis.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Jasielec
authors.affiliation: Division of Biostatistics, Washington University School of Medicine in St. Louis.
authors.forename: Chengjie
authors.initials: C
authors.lastname: Xiong
authors.affiliation: Division of Biostatistics, Washington University School of Medicine in St. Louis.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Grant
authors.affiliation: Department of Neurology, Washington University School of Medicine in St. Louis.
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000503:physiopathology*; D015415:Biomarkers; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D061212:Memory, Episodic; D011214:Practice, Psychological; D062706:Prodromal Symptoms; D011597:Psychomotor Performance / Q000502:physiology*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers