title: Sensitivity to change and prediction of global change for the Alzheimer's Questionnaire.
abstract: BACKGROUND
  Longitudinal assessment of cognitive decline in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) often involves the use of both informant-based and objective cognitive assessments. As efforts have focused on identifying individuals in pre-clinical stages, instruments that are sensitive to subtle cognitive changes are needed. The Alzheimer's Questionnaire (AQ) has demonstrated high sensitivity and specificity in identifying aMCI and AD; however its ability to measure longitudinal change has not been assessed. The aims of this study are to assess the sensitivity to change of the AQ and to determine whether the AQ predicts change in global cognition and function in cognitively normal (CN), aMCI, and AD subjects.
  
  
  METHODS
  Data from 202 individuals participating in a brain and body donation program were utilized for this study (101 CN, 62 aMCI, 39 AD). AD and aMCI individuals were matched on age, education, and gender to CN individuals. Sensitivity to change of the AQ was assessed in addition to the AQ's ability to predict change in global cognition and function. The Mini Mental State Exam (MMSE) and Functional Activities Questionnaire (FAQ) were used as gold standard comparisons of cognition and function. Sample size calculations for a 25% treatment effect were also carried out for all three groups.
  
  
  RESULTS
  The AQ demonstrated small sensitivity to change in the aMCI and CN groups (d = 0.33, d = 0.23, respectively) and moderate sensitivity to change in the AD group (d = 0.43). The AQ was associated with increases in the Clinical Dementia Rating Global Score (OR = 1.20 (1.09, 1.32), P <0.001). Sample size calculations found that the AQ would require substantially fewer subjects than the MMSE given a 25% treatment effect.
  
  
  CONCLUSIONS
  Although the AQ demonstrated small sensitivity to change in aMCI and CN individuals in terms of effect size, the AQ may be superior to objective cognitive tests in terms of required sample size for a clinical trial. As clinicians and researchers continue to identify and treat individuals in earlier stages of AD, there is a need for instruments that are sensitive to cognitive changes in these earlier stages.
authors.affiliation: The Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ, 85351, USA. michael.ahmadi@bannerhealth.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Malek-Ahmadi
authors.affiliation: Banner Alzheimer's Institute, Phoenix, AZ, 85006, USA. kewei.chen@bannerhealth.com.
authors.forename: Kewei
authors.initials: K
authors.lastname: Chen
authors.affiliation: The Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ, 85351, USA. kathryn.davis@bannerhealth.com.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Davis
authors.affiliation: The Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ, 85351, USA. christine.belden@bannerhealth.com.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Belden
authors.affiliation: The Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ, 85351, USA. jessica.powell@bannerhealth.com.
authors.forename: Jessica
authors.initials: J
authors.lastname: Powell
authors.affiliation: The Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ, 85351, USA. sandra.jacobson@bannerhealth.com.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Jacobson
authors.affiliation: The Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ, 85351, USA. marwan.sabbagh@bannerhealth.com.
authors.forename: Marwan N
authors.initials: MN
authors.lastname: Sabbagh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000503:physiopathology*; D000647:Amnesia / Q000503:physiopathology; D001921:Brain / Q000503:physiopathology; D003071:Cognition / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012680:Sensitivity and Specificity; D011795:Surveys and Questionnaires