title: The trajectory of cognitive decline in the pre-dementia phase in memory clinic visitors: findings from the 4C-MCI study.
abstract: BACKGROUND
  We investigated the course of decline in multiple cognitive domains in non-demented subjects from a memory clinic setting, and compared pattern, onset and magnitude of decline between subjects who progressed to Alzheimer's disease (AD) dementia at follow-up and subjects who did not progress.
  
  
  METHODS
  In this retrospective cohort study 819 consecutive non-demented patients who visited the memory clinics in Maastricht or Amsterdam between 1987 and 2010 were followed until they became demented or for a maximum of 10 years (range 0.5-10 years). Differences in trajectories of episodic memory, executive functioning, verbal fluency, and information processing speed/attention between converters to AD dementia and subjects remaining non-demented were compared by means of random effects modelling.
  
  
  RESULTS
  The cognitive performance of converters and non-converters could already be differentiated seven (episodic memory) to three (verbal fluency and executive functioning) years prior to dementia diagnosis. Converters declined in these three domains, while non-converters remained stable on episodic memory and executive functioning and showed modest decline in verbal fluency. There was no evidence of decline in information processing speed/attention in either group.
  
  
  CONCLUSIONS
  Differences in cognitive performance between converters to AD dementia and subjects remaining non-demented could be established 7 years prior to diagnosis for episodic memory, with verbal fluency and executive functioning following several years later. Therefore, in addition to early episodic memory decline, decline in executive functions may also flag incident AD dementia. By contrast, change in information processing speed/attention seems less informative.
authors.affiliation: Alzheimer Centre Limburg, School for Mental Health and Neuroscience, Maastricht University Medical Centre,Maastricht,The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Hamel
authors.affiliation: Alzheimer Centre Limburg, School for Mental Health and Neuroscience, Maastricht University Medical Centre,Maastricht,The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Köhler
authors.affiliation: Department of Neurology and Neuroscience Campus Amsterdam,VUmc Alzheimer Centre, VUmc Medical Centre,Amsterdam,The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Sistermans
authors.affiliation: Department of Medical Psychology and Neuroscience Campus Amsterdam,VUmc Alzheimer Centre, VUmc Medical Centre,Amsterdam,The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Koene
authors.affiliation: Department of Neurology and Neuroscience Campus Amsterdam,VUmc Alzheimer Centre, VUmc Medical Centre,Amsterdam,The Netherlands.
authors.forename: Y
authors.initials: Y
authors.lastname: Pijnenburg
authors.affiliation: Department of Neurology and Neuroscience Campus Amsterdam,VUmc Alzheimer Centre, VUmc Medical Centre,Amsterdam,The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: van der Flier
authors.affiliation: Department of Neurology and Neuroscience Campus Amsterdam,VUmc Alzheimer Centre, VUmc Medical Centre,Amsterdam,The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Alzheimer Centre Limburg, School for Mental Health and Neuroscience, Maastricht University Medical Centre,Maastricht,The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Aalten
authors.affiliation: Alzheimer Centre Limburg, School for Mental Health and Neuroscience, Maastricht University Medical Centre,Maastricht,The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Verhey
authors.affiliation: Alzheimer Centre Limburg, School for Mental Health and Neuroscience, Maastricht University Medical Centre,Maastricht,The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Visser
authors.affiliation: Alzheimer Centre Limburg, School for Mental Health and Neuroscience, Maastricht University Medical Centre,Maastricht,The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Ramakers
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000503:physiopathology*; D003072:Cognition Disorders / Q000453:epidemiology / Q000503:physiopathology*; D060825:Cognitive Dysfunction / Q000453:epidemiology / Q000503:physiopathology*; D018450:Disease Progression; D056344:Executive Function / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D061212:Memory, Episodic; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D062706:Prodromal Symptoms; D011597:Psychomotor Performance / Q000502:physiology*
keywords: neuropsychology