title: Relationships between performance on the Cogstate Brief Battery, neurodegeneration, and Aβ accumulation in cognitively normal older adults and adults with MCI.
abstract: We investigated the extent to which decline in memory and working memory in beta-amyloid (Aβ) positive non-demented individuals was related to hippocampal atrophy and Aβ accumulation over 36 months. Cognitively normal older adults (CN) (n = 178) and adults with mild cognitive impairment (MCI) (n = 49) underwent positron emission tomography neuroimaging, magnetic resonance imaging, and cognitive assessments at baseline, 18- and 36-months. Relative to Aβ- CNs, Aβ+ CNs and Aβ+ MCIs showed greater rates of cognitive decline, Aβ accumulation, and hippocampal atrophy. Analysis of interrelationships between these Alzheimer's disease markers in Aβ+ CNs and MCIs indicated that rate of Aβ accumulation was associated with rate of hippocampal atrophy (β = -0.05, p = .037), which was in turn associated independently with rate of decline in memory (β = -0.03, p = .032). This suggests that Aβ accumulation precedes any neurodegeneration or clinical symptoms, and that the relationship between Aβ and cognitive decline is mediated by hippocampal atrophy.
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia Department of Neurology, Warren Alpert School of Medicine, Brown University, Providence, RI, USA yen_ying_lim@brown.edu.
authors.forename: Yen Ying
authors.initials: YY
authors.lastname: Lim
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: Commonwealth Scientific Industrial Research Organization Preventative Health National Research Flagship, Australian e-Health Research Centre-BioMedIA, Brisbane, QLD, Australia.
authors.forename: Pierrick
authors.initials: P
authors.lastname: Bourgeat
authors.affiliation: Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, Kew, VIC, Australia National Ageing Research Institute, Parkville, VIC, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, Kew, VIC, Australia National Ageing Research Institute, Parkville, VIC, Australia.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Ellis
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Rembach
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Karra
authors.initials: K
authors.lastname: Harrington
authors.affiliation: Commonwealth Scientific Industrial Research Organization Preventative Health National Research Flagship, Australian e-Health Research Centre-BioMedIA, Brisbane, QLD, Australia.
authors.forename: Olivier
authors.initials: O
authors.lastname: Salvado
authors.affiliation: Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, WA, Australia.
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.affiliation: Department of Neurology, Warren Alpert School of Medicine, Brown University, Providence, RI, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Snyder
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, VIC, 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, VIC, Australia Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, VIC, Australia.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia Cogstate Ltd., Melbourne, VIC, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Maruff
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D001057:Apolipoproteins E / Q000235:genetics; D001284:Atrophy / Q000209:etiology; D002247:Carbon Isotopes; D060825:Cognitive Dysfunction / Q000150:complications* / Q000000981:diagnostic imaging; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000175:diagnosis / Q000209:etiology*; D008570:Memory, Short-Term / Q000502:physiology; D008875:Middle Aged; D009410:Nerve Degeneration / Q000209:etiology* / Q000473:pathology; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D013844:Thiazoles; D013997:Time Factors
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D001057:Apolipoproteins E; D002247:Carbon Isotopes; D013844:Thiazoles
keywords: Episodic memory; Hippocampal volume; MCI; Neuropsychological assessment; Preclinical AD; β-amyloid