title: Sensitivity of composite scores to amyloid burden in preclinical Alzheimer's disease: Introducing the Z-scores of Attention, Verbal fluency, and Episodic memory for Nondemented older adults composite score.
abstract: BACKGROUND
  Cognitive composite scores developed for preclinical Alzheimer's disease (AD) often consist of multiple cognitive domains as they may provide greater sensitivity to detect β-amyloid (Aβ)-related cognitive decline than episodic memory (EM) composite scores alone. However, this has never been empirically tested. We compared the rate of cognitive decline associated with high Aβ (Aβ+) and very high Aβ (Aβ++) in cognitively normal (CN) older adults on three multidomain cognitive composite scores and one single-domain (EM) composite score.
  
  
  METHODS
  CN older adults (n = 423) underwent Aβ neuroimaging and completed neuropsychological assessments at baseline, and at 18-, 36-, 54-, and 72-month follow-ups. Four cognitive composite scores were computed: the ADCS-PACC (ADCS-Preclinical Alzheimer Cognitive Composite), ADCS-PACC without the inclusion of the mini-mental state examination (MMSE), an EM composite, and the Z-scores of Attention, Verbal fluency, and Episodic memory for Nondemented older adults (ZAVEN) composite.
  
  
  RESULTS
  Compared with Aβ+ CN older adults, Aβ++ CN older adults showed faster rates of decline across all cognitive composites, with the largest decline observed for ZAVEN composite (d = 1.07). Similarly, compared with Aβ- CN older adults, Aβ+ CN older adults also showed faster rates of cognitive decline, but only for the ADCS-PACC no MMSE (d = 0.43), EM (d = 0.53), and ZAVEN (d = 0.50) composites.
  
  
  CONCLUSIONS
  Aβ-related cognitive decline is best detected using validated neuropsychological instruments. Removal of the MMSE from the ADCS-PACC and replacing it with a test of executive function (verbal fluency; i.e., the ZAVEN) rendered this composite more sensitive even in detecting Aβ-related cognitive decline between Aβ+ and Aβ++ CN older adults.
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Yen Ying
authors.initials: YY
authors.lastname: Lim
authors.affiliation: Department of Neurology, Warren Alpert School of Medicine, Brown University, Providence, RI, USA; Interdisciplinary Neuroscience Program, University of Rhode Island, Kingston, RI, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Snyder
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Pietrzak
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Albulene
authors.initials: A
authors.lastname: Ukiqi
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia; Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.affiliation: Academic Unit for Psychiatry of Old Age, St. Vincent's Health, The University of Melbourne, Kew, Victoria, Australia; National Ageing Research Institute, Parkville, Victoria, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.affiliation: Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship, Australian e-Health Research Centre-BioMedIA, Brisbane, Queensland, Australia.
authors.forename: Olivier
authors.initials: O
authors.lastname: Salvado
authors.affiliation: Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship, Australian e-Health Research Centre-BioMedIA, Brisbane, Queensland, Australia.
authors.forename: Pierrick
authors.initials: P
authors.lastname: Bourgeat
authors.affiliation: Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia, Australia.
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia; Cogstate Ltd., Melbourne, Victoria, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Maruff
keywords: Amyloid; Cognitive composite; Cognitive decline; Neuropsychological assessment; Preclinical Alzheimer's disease