title: Amyloid-Related Memory Decline in Preclinical Alzheimer's Disease Is Dependent on APOE ε4 and Is Detectable over 18-Months.
abstract: High levels of β-amyloid (Aβ) in the brain and carriage of the APOE ε4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. However, the relationship between these two biomarkers and cognitive decline is unclear. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE ε4 carrier status, and cognitive decline over 18 months, in 317 cognitively healthy (CN) older adults (47.6% males, 52.4% females) aged between 60 and 89 years (Mean = 69.9, SD = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults with high Aβ who were also APOE ε4 carriers demonstrated the most pronounced decline in learning and working memory. In CN older adults who were APOE ε4 non-carriers, high Aβ was unrelated to cognitive decline in learning and working memory. Carriage of APOE ε4 in CN older adults with low Aβ was associated with a significantly increased rate of decline in learning and unexpectedly, improved cognitive performance on measures of verbal episodic memory over 18 months. These results suggest that Aβ and APOE ε4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE ε4 as biomarkers of early Alzheimer's disease.
authors.affiliation: Department of Psychology, Royal Melbourne Institute of Technology, Melbourne, Australia.
authors.forename: Christine
authors.initials: C
authors.lastname: Thai
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Department of Neurology, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island, United States of America; Department of Neurology, Rhode Island Hospital, Providence, Rhode Island, United States of America.
authors.forename: Yen Ying
authors.initials: YY
authors.lastname: Lim
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, 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: Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia, Australia; Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Western Australia, Australia; Co-operative Research Centre for Mental Health, Perth, Western Australia, Australia.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Laws
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: The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; 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: Kathryn A
authors.initials: KA
authors.lastname: Ellis
authors.affiliation: Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia, Australia; Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Western Australia, Australia.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Rainey-Smith
authors.affiliation: Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia, Australia; Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Western Australia, Australia.
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, 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, Parkville, Victoria, Australia; Cogstate Ltd., Melbourne, Victoria, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Maruff
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000235:genetics / Q000523:psychology*; D008875:Middle Aged
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4