title: ADCOMS: a composite clinical outcome for prodromal Alzheimer's disease trials.
abstract: Development of new therapies for Alzheimer's disease (AD) is increasingly focused on more mildly affected populations, and requires new assessment and outcome strategies. Patients in early stages of AD have mild cognitive decline and no, or limited, functional impairment. To respond to these assessment challenges, we developed a measurement approach based on established scale items that exhibited change in previous amnestic Mild Cognitive Impairment (aMCI) trials.
  
  
  
  Partial least squares regression with a longitudinal clinical decline model identified items from commonly used clinical scales with the highest combined sensitivity to change over time in aMCI and weighted these items according to their relative contribution to detecting clinical progression in patients' early stages of AD. The resultant AD Composite Score (ADCOMS) was assessed for its ability to detect treatment effect in aMCI/prodromal AD (pAD) clinical trial populations.
  
  
  
  ADCOMS consists of 4 Alzheimer's Disease Assessment Scale-cognitive subscale items, 2 Mini-Mental State Examination items, and all 6 Clinical Dementia Rating-Sum of Boxes items. ADCOMS demonstrated improved sensitivity to clinical decline over individual scales in pAD, aMCI and in mild AD dementia. ADCOMS also detected treatment effects associated with the use of cholinesterase inhibitors in these populations. Improved sensitivity predicts smaller sample size requirements when ADCOMS is used in early AD trials.
  
  
  
  ADCOMS is proposed as new standard outcome for pAD and mild AD dementia trials, and is progressing in a CAMD-sponsored qualification process for use in registration trials of pAD.
authors.affiliation: Department of Neuroscience and General Medicine, Eisai Inc., Woodcliff Lake, New York, USA.
authors.forename: Jinping
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neuroscience and General Medicine, Eisai Inc., Woodcliff Lake, New York, USA.
authors.forename: Veronika
authors.initials: V
authors.lastname: Logovinsky
authors.affiliation: Pentara Corp., Salt Lake City, Utah, USA.
authors.forename: Suzanne B
authors.initials: SB
authors.lastname: Hendrix
authors.affiliation: Pentara Corp., Salt Lake City, Utah, USA.
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Stanworth
authors.affiliation: Department of Neuroscience and General Medicine, Eisai Inc., Woodcliff Lake, New York, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Perdomo
authors.affiliation: Department of Neuroscience and General Medicine, Eisai Inc., Woodcliff Lake, New York, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Neuroscience and General Medicine, Eisai Inc., Woodcliff Lake, New York, USA.
authors.forename: Shobha
authors.initials: S
authors.lastname: Dhadda
authors.affiliation: Department of Neuroscience and General Medicine, Eisai Inc., Woodcliff Lake, New York, USA.
authors.forename: Ira
authors.initials: I
authors.lastname: Do
authors.affiliation: Department of Neuroscience and General Medicine, Eisai Inc., Woodcliff Lake, New York, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Rabe
authors.affiliation: Department of Neuroscience and General Medicine, Eisai Inc., Woodcliff Lake, New York, USA.
authors.forename: Johan
authors.initials: J
authors.lastname: Luthman
authors.affiliation: Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, Nevada, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cummings
authors.affiliation: Department of Neuroscience and General Medicine, Eisai Inc., Woodcliff Lake, New York, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Satlin
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D016229:Amyloid beta-Peptides; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000175:diagnosis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D011569:Psychiatric Status Rating Scales
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers