title: APOE ε4 moderates amyloid-related memory decline in preclinical Alzheimer's disease.
abstract: The apolipoprotein E (APOE) ɛ4 allele and high levels of beta-amyloid (Aβ) are associated with episodic memory decline and risk for Alzheimer's disease. However, there is debate about independent or interactive effects of ɛ4 on Aβ-related memory decline in healthy older adults. Healthy older adults with high Aβ burden (n = 84) enrolled in Australian Imaging, Biomarkers, and Lifestyle Study were included in this study. Cognition was measured using the computerized Cogstate Brief Battery at baseline, 18-, 36-, and 54-month follow-ups. Mini Mental State Examination and Clinical Dementia Rating scales were also administered at baseline and each follow-up timepoint. Relative to Aβ+ ɛ4 noncarriers (n = 36), Aβ+ ɛ4 carriers (n = 48) showed significantly faster decline on memory tasks, which was by convention, moderate in magnitude (d = 0.40-0.47). Aβ positivity coupled with APOE ɛ4 was associated with moderately increased decline in memory over a 54-month assessment period, suggesting that, in the preclinical stages of Alzheimer's disease, the manifestation of memory decline in older adults with high Aβ is exacerbated by the presence of APOE ɛ4.
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia; Department of Neurology, Warren Alpert School of Medicine, Brown University, Providence, RI, USA; Department of Neurology, Rhode Island Hospital, Providence, RI, USA. Electronic address: yen_ying_lim@brown.edu.
authors.forename: Yen Ying
authors.initials: YY
authors.lastname: Lim
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: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Pietrzak
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, The University of Melbourne, 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: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Karra
authors.initials: K
authors.lastname: Harrington
authors.affiliation: Department of Neurology, Warren Alpert School of Medicine, Brown University, Providence, RI, USA; Department of Neurology, Rhode Island Hospital, Providence, RI, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Snyder
authors.affiliation: 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, 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
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D061212:Memory, Episodic; D008875:Middle Aged; D009483:Neuropsychological Tests; D012306:Risk; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4
keywords: Apolipoprotein E; Beta-amyloid; Cognitive decline; Memory; Preclinical Alzheimer's disease