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

Yen Ying Lim1, Peter J. Snyder2,3, Robert H. Pietrzak4, Albulene Ukiqi1, Victor L. Villemagne1,5,6, David Ames7,8, Olivier Salvado9, Pierrick Bourgeat9, Ralph N. Martins10, Colin L. Masters1, Christopher C. Rowe5,6, Paul Maruff1,11
1The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia
2Department of Neurology, Warren Alpert School of Medicine, Brown University, Providence, RI, USA
3Interdisciplinary Neuroscience Program, University of Rhode Island, Kingston, RI, USA
4Department of Psychiatry; Yale University School of Medicine; New Haven CT USA
5Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia
6Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
7Academic Unit for Psychiatry of Old Age, St. Vincent's Health, The University of Melbourne, Kew, Victoria, Australia
8National Ageing Research Institute, Parkville, Victoria, Australia
9Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship, Australian e-Health Research Centre-BioMedIA, Brisbane, Queensland, Australia
10Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia, Australia
11Cogstate Ltd., Melbourne, Victoria, Australia

Tóm tắt

AbstractIntroductionCognitive 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.MethodsCN 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.ResultsCompared 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.DiscussionAβ‐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.

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