title: Empirically Defining Trajectories of Late-Life Cognitive and Functional Decline.
abstract: BACKGROUND
  Alzheimer's disease (AD) is associated with variable cognitive and functional decline, and it is difficult to predict who will develop the disease and how they will progress.
  
  
  OBJECTIVE
  This exploratory study aimed to define latent classes from participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database who had similar growth patterns of both cognitive and functional change using Growth Mixture Modeling (GMM), identify characteristics associated with those trajectories, and develop a decision tree using clinical predictors to determine which trajectory, as determined by GMM, individuals will most likely follow.
  
  
  METHODS
  We used ADNI early mild cognitive impairment (EMCI), late MCI (LMCI), AD dementia, and healthy control (HC) participants with known amyloid-β status and follow-up assessments on the Alzheimer's Disease Assessment Scale - Cognitive Subscale or the Functional Activities Questionnaire (FAQ) up to 24 months postbaseline. GMM defined trajectories. Classification and Regression Tree (CART) used certain baseline variables to predict likely trajectory path.
  
  
  RESULTS
  GMM identified three trajectory classes (C): C1 (n = 162, 13.6%) highest baseline impairment and steepest pattern of cognitive/functional decline; C3 (n = 819, 68.7%) lowest baseline impairment and minimal change on both; C2 (n = 211, 17.7%) intermediate pattern, worsening on both, but less steep than C1. C3 had fewer amyloid- or apolipoprotein-E ɛ4 (APOE4) positive and more healthy controls (HC) or EMCI cases. CART analysis identified two decision nodes using the FAQ to predict likely class with 82.3% estimated accuracy.
  
  
  CONCLUSIONS
  Cognitive/functional change followed three trajectories with greater baseline impairment and amyloid and APOE4 positivity associated with greater progression. FAQ may predict trajectory class.
authors.affiliation: Eli Lilly and Company or a Wholly Owned subsidiary, Indianapolis, IN, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Hochstetler
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Paula T
authors.initials: PT
authors.lastname: Trzepacz
authors.affiliation: Eli Lilly and Company or a Wholly Owned subsidiary, Indianapolis, IN, USA.
authors.forename: Shufang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Eli Lilly and Company or a Wholly Owned subsidiary, Indianapolis, IN, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.affiliation: Eli Lilly and Company or a Wholly Owned subsidiary, Indianapolis, IN, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Case
authors.affiliation: Eli Lilly and Company or a Wholly Owned subsidiary, Indianapolis, IN, USA.|Indiana University School of Medicine, Indianapolis, IN, USA.|Indiana University Physician Group, Indiana University Health, Indianapolis, IN, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Henley
authors.affiliation: Indiana University Physician Group, Indiana University Health, Indianapolis, IN, USA.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Degenhardt
authors.affiliation: Johns Hopkins University and Johns Hopkins Bayview, Baltimore, MD, USA.
authors.forename: Jeannie-Marie
authors.initials: JM
authors.lastname: Leoutsakos
authors.affiliation: Johns Hopkins University and Johns Hopkins Bayview, Baltimore, MD, USA.
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Lyketsos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000175:diagnosis*; D053327:Apolipoprotein E4; D003072:Cognition Disorders / Q000175:diagnosis* / Q000503:physiopathology*; D016208:Databases, Factual / Q000706:statistics & numerical data; D003704:Dementia / Q000175:diagnosis*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D009483:Neuropsychological Tests; D011795:Surveys and Questionnaires
chemical_list: D053327:Apolipoprotein E4
keywords: ADNI; Alzheimer’s disease; MCI; amyloid; cognition; disease progression; function; longitudinal studies