title: The 12 Years Preceding Mild Cognitive Impairment Due to Alzheimer's Disease: The Temporal Emergence of Cognitive Decline.
abstract: BACKGROUND
  The identification of the type and sequence of cognitive decline in preclinical mild cognitive impairment (MCI) prior to Alzheimer's disease (AD) is crucial for understanding AD pathogenesis and implementing therapeutic interventions.
  
  
  OBJECTIVE
  To model the longitudinal courses of different neuropsychological functions in MCI due to AD.
  
  
  METHODS
  We investigated the prodromal phase of MCI over a 12-year period in 27 initially healthy participants with subsequent MCI preceding AD (NC-MCI) and 60 demographically matched healthy individuals (NC-NC). The longitudinal courses of cognitive performance (verbal and visual episodic memory, semantic memory, executive functioning, constructional praxis, psychomotor speed, language, and informant-based reports) were analyzed with linear mixed effects models.
  
  
  RESULTS
  The sequence with which different cognitive functions declined in the NC-MCI relative to the NC-NC group began with verbal memory and savings performance approximately eight years, and verbal episodic learning, visual memory, and semantic memory (animal fluency) circa four years prior to the MCI diagnosis. Executive functioning, psychomotor speed, and informant-based reports of the NC-MCI group declined approximately two years preceding the MCI diagnosis.
  
  
  CONCLUSIONS
  Measurable neuropsychological deterioration occurs up to approximately eight years preceding MCI due to AD.
authors.affiliation: Memory Clinic, University Center for Medicine of Aging Basel, Felix Platter Hospital, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Panagiota
authors.initials: P
authors.lastname: Mistridis
authors.affiliation: Memory Clinic, University Center for Medicine of Aging Basel, Felix Platter Hospital, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Krumm
authors.affiliation: Memory Clinic, University Center for Medicine of Aging Basel, Felix Platter Hospital, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Andreas U
authors.initials: AU
authors.lastname: Monsch
authors.affiliation: Department of Mathematics and Technology, University of Applied Sciences Koblenz, Koblenz, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Berres
authors.affiliation: Memory Clinic, University Center for Medicine of Aging Basel, Felix Platter Hospital, Basel, Switzerland.|University of Basel, Basel, Switzerland.|Centre for Speech, Language and the Brain, Department of Experimental Psychology, University of Cambridge, Cambridge, UK.
authors.forename: Kirsten I
authors.initials: KI
authors.lastname: Taylor
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000453:epidemiology / Q000523:psychology*; D003071:Cognition; D060825:Cognitive Dysfunction / Q000453:epidemiology / Q000209:etiology / Q000523:psychology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D062706:Prodromal Symptoms; D013557:Switzerland / Q000453:epidemiology; D013997:Time Factors
keywords: Alzheimer’s disease; cognitive decline; linear mixed effects models; longitudinal course; mild cognitive impairment; neuropsychology; prodromal