title: Cognitive Impairment Precedes and Predicts Functional Impairment in Mild Alzheimer's Disease.
abstract: BACKGROUND
  The temporal relationship of cognitive deficit and functional impairment in Alzheimer's disease (AD) is not well characterized. Recent analyses suggest cognitive decline predicts subsequent functional decline throughout AD progression.
  
  
  OBJECTIVE
  To better understand the relationship between cognitive and functional decline in mild AD using autoregressive cross-lagged (ARCL) panel analyses in several clinical trials.
  
  
  METHODS
  Data included placebo patients with mild AD pooled from two multicenter, double-blind, Phase 3 solanezumab (EXPEDITION/2) or semagacestat (IDENTITY/2) studies, and from AD patients participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cognitive and functional outcomes were assessed using AD Assessment Scale-Cognitive subscale (ADAS-Cog), AD Cooperative Study-Activities of Daily Living instrumental subscale (ADCS-iADL), or Functional Activities Questionnaire (FAQ), respectively. ARCL panel analyses evaluated relationships between cognitive and functional impairment over time.
  
  
  RESULTS
  In EXPEDITION, ARCL panel analyses demonstrated cognitive scores significantly predicted future functional impairment at 5 of 6 time points, while functional scores predicted subsequent cognitive scores in only 1 of 6 time points. Data from IDENTITY and ADNI programs yielded consistent results whereby cognition predicted subsequent function, but not vice-versa.
  
  
  CONCLUSIONS
  Analyses from three databases indicated cognitive decline precedes and predicts subsequent functional decline in mild AD dementia, consistent with previously proposed hypotheses, and corroborate recent publications using similar methodologies. Cognitive impairment may be used as a predictor of future functional impairment in mild AD dementia and can be considered a critical target for prevention strategies to limit future functional decline in the dementia process.
authors.affiliation: Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu-Seifert
authors.affiliation: Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Siemers
authors.affiliation: Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Price
authors.affiliation: Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, USA.
authors.forename: Baoguang
authors.initials: B
authors.lastname: Han
authors.affiliation: Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, USA.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Selzler
authors.affiliation: Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, USA.|Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: David
authors.initials: D
authors.lastname: Henley
authors.affiliation: Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Sundell
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, CA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Aisen
authors.affiliation: Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cummings
authors.affiliation: Eli Lilly Canada, Toronto, Canada.
authors.forename: Joel
authors.initials: J
authors.lastname: Raskin
authors.affiliation: Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Mohs
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000544:Alzheimer Disease / Q000150:complications* / Q000188:drug therapy / Q000523:psychology*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001381:Azepines / Q000627:therapeutic use; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014150:Antipsychotic Agents; D001381:Azepines; C484278:N2-((2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl)-N1-((7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-L-alaninamide; C550616:solanezumab; D000409:Alanine
keywords: Activities of daily living; Alzheimer’s disease; Phase 3 clinical trials; cognition; correlation of data; dementia; function; solanezumab