title: Development of a straightforward and sensitive scale for MCI and early AD clinical trials.
abstract: BACKGROUND
  Although the Clinical Dementia Rating Scale-Sum of Boxes score (CDR-SB) is a widely accepted and commonly used global scale, validated clinical endpoints of cognitive changes are unavailable in the predementia stages of Alzheimer's disease (AD), and a new clinical assessment with reliability and sensitivity is needed in the mild cognitive impairment (MCI) population.
  
  
  METHODS
  Using Alzheimer's Disease Neuroimaging Initiative (ADNI)-1/GO data, signal-to-noise ratios (SNRs) were calculated to quantify the sensitivity of a measure for detecting disease progression and hypothetical treatment effects. All possible combinations of selected sensitive measures were assessed for developing composite scores. The analyses were performed in the MCI population and subpopulations enriched by apolipoprotein E4 (APOE ε4), hippocampal volume, and cerebrospinal fluid β-amyloid.
  
  
  RESULTS
  The best composite score was "Word Recall + Delayed Word Recall + Orientation + CDR-SB + FAQ", more sensitive than 13-item Alzheimer's Disease Assessment Scale-cognitive subscale or CDR-SB.
  
  
  CONCLUSIONS
  The proposed composite score derived from the existing clinical endpoints demonstrated higher sensitivity in the MCI population and is easy to implement and standardize across studies.
authors.affiliation: Pfizer, Inc., Groton, CT, USA. Electronic address: yifan.huang@pfizer.com.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Pfizer, Inc., Groton, CT, USA.
authors.forename: Kaori
authors.initials: K
authors.lastname: Ito
authors.affiliation: Pfizer, Inc., Groton, CT, USA; SystaMedic, Inc., Groton, CT, USA.
authors.forename: Clare B
authors.initials: CB
authors.lastname: Billing
authors.affiliation: Pfizer, Inc., Groton, CT, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Anziano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics; D002986:Clinical Trials as Topic; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D017063:Outcome Assessment, Health Care; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011569:Psychiatric Status Rating Scales; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's Disease Assessment Scale-cognitive subscale; Alzheimer's disease; Clinical trials; Composite endpoints; Mild cognitive impairment; Signal-to-noise ratio