title: Aβ-related memory decline in APOE ε4 noncarriers: Implications for Alzheimer disease.
abstract: As the absence of Aβ-related memory decline in APOE ε4 noncarriers may be due to the relative brevity of previous studies, we aimed to characterize Aβ-related cognitive decline over 72 months in APOE ε4 carriers and noncarriers who were cognitively normal (CN).
  
  
  
  CN older adults (n = 423) underwent Aβ imaging and APOE genotyping. Participants completed comprehensive neuropsychological testing at baseline 18-, 36-, 54-, and 72-month assessments.
  
  
  
  Relative to Aβ- CN ε4 noncarriers, both Aβ+ CN ε4 carriers and noncarriers showed significantly increased decline in measures of memory, language, and executive function as well as higher rates of progression to a clinical classification of mild cognitive impairment. Memory decline was greater in Aβ+ CN ε4 carriers than in Aβ+ CN ε4 noncarriers. No cognitive decline was evident in Aβ- CN ε4 carriers.
  
  
  
  In CN older adults, Aβ+ is associated with memory decline in ε4 noncarriers; however, the rate of this decline is much slower than that observed in ε4 carriers. These data indicate that the processes by which ε4 carriage increases the rate of Aβ-related cognitive decline occur in the preclinical stage of Alzheimer disease.
authors.affiliation: From The Florey Institute of Neuroscience and Mental Health (Y.Y.L., V.L.V., C.F., C.L.M., P.M.), The University of Melbourne, Parkville; Centre of Excellence for Alzheimer's Disease Research and Care (S.M.L., T.P., S.R.-S., R.N.M.), Edith Cowan University, Joondalup, Australia; Department of Psychiatry (R.H.P.), Yale University School of Medicine, New Haven, CT; Academic Unit for Psychiatry of Old Age (D.A.), St. Vincent's Health, The University of Melbourne, Kew; National Ageing Research Institute (D.A.), Parkville, Australia; Department of Neurology (P.J.S.), Warren Alpert Medical School of Brown University, Providence, RI; Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship (O.S., P.B.), Australian e-Health Research Centre-BiaMedIA, Brisbane; Departments of Nuclear Medicine and Centre for PET (V.L.V., C.C.R.) and Medicine (V.L.V., C.C.R.), Austin Health, Heidelberg; Sir James McCusker Alzheimer's Disease Research Unit (S.M.L., T.P.), Hollywood Private Hospital, Perth; Co-operative Research Centre for Mental Health (S.M.L., T.P.), Carlton South; and CogState Ltd. (P.M.), Melbourne, Australia. yen.lim@florey.edu.au.
authors.forename: Yen Ying
authors.initials: YY
authors.lastname: Lim
authors.affiliation: From The Florey Institute of Neuroscience and Mental Health (Y.Y.L., V.L.V., C.F., C.L.M., P.M.), The University of Melbourne, Parkville; Centre of Excellence for Alzheimer's Disease Research and Care (S.M.L., T.P., S.R.-S., R.N.M.), Edith Cowan University, Joondalup, Australia; Department of Psychiatry (R.H.P.), Yale University School of Medicine, New Haven, CT; Academic Unit for Psychiatry of Old Age (D.A.), St. Vincent's Health, The University of Melbourne, Kew; National Ageing Research Institute (D.A.), Parkville, Australia; Department of Neurology (P.J.S.), Warren Alpert Medical School of Brown University, Providence, RI; Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship (O.S., P.B.), Australian e-Health Research Centre-BiaMedIA, Brisbane; Departments of Nuclear Medicine and Centre for PET (V.L.V., C.C.R.) and Medicine (V.L.V., C.C.R.), Austin Health, Heidelberg; Sir James McCusker Alzheimer's Disease Research Unit (S.M.L., T.P.), Hollywood Private Hospital, Perth; Co-operative Research Centre for Mental Health (S.M.L., T.P.), Carlton South; and CogState Ltd. (P.M.), Melbourne, Australia.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Laws
authors.affiliation: From The Florey Institute of Neuroscience and Mental Health (Y.Y.L., V.L.V., C.F., C.L.M., P.M.), The University of Melbourne, Parkville; Centre of Excellence for Alzheimer's Disease Research and Care (S.M.L., T.P., S.R.-S., R.N.M.), Edith Cowan University, Joondalup, Australia; Department of Psychiatry (R.H.P.), Yale University School of Medicine, New Haven, CT; Academic Unit for Psychiatry of Old Age (D.A.), St. Vincent's Health, The University of Melbourne, Kew; National Ageing Research Institute (D.A.), Parkville, Australia; Department of Neurology (P.J.S.), Warren Alpert Medical School of Brown University, Providence, RI; Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship (O.S., P.B.), Australian e-Health Research Centre-BiaMedIA, Brisbane; Departments of Nuclear Medicine and Centre for PET (V.L.V., C.C.R.) and Medicine (V.L.V., C.C.R.), Austin Health, Heidelberg; Sir James McCusker Alzheimer's Disease Research Unit (S.M.L., T.P.), Hollywood Private Hospital, Perth; Co-operative Research Centre for Mental Health (S.M.L., T.P.), Carlton South; and CogState Ltd. (P.M.), Melbourne, Australia.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.affiliation: From The Florey Institute of Neuroscience and Mental Health (Y.Y.L., V.L.V., C.F., C.L.M., P.M.), The University of Melbourne, Parkville; Centre of Excellence for Alzheimer's Disease Research and Care (S.M.L., T.P., S.R.-S., R.N.M.), Edith Cowan University, Joondalup, Australia; Department of Psychiatry (R.H.P.), Yale University School of Medicine, New Haven, CT; Academic Unit for Psychiatry of Old Age (D.A.), St. Vincent's Health, The University of Melbourne, Kew; National Ageing Research Institute (D.A.), Parkville, Australia; Department of Neurology (P.J.S.), Warren Alpert Medical School of Brown University, Providence, RI; Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship (O.S., P.B.), Australian e-Health Research Centre-BiaMedIA, Brisbane; Departments of Nuclear Medicine and Centre for PET (V.L.V., C.C.R.) and Medicine (V.L.V., C.C.R.), Austin Health, Heidelberg; Sir James McCusker Alzheimer's Disease Research Unit (S.M.L., T.P.), Hollywood Private Hospital, Perth; Co-operative Research Centre for Mental Health (S.M.L., T.P.), Carlton South; and CogState Ltd. (P.M.), Melbourne, Australia.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Pietrzak
authors.affiliation: From The Florey Institute of Neuroscience and Mental Health (Y.Y.L., V.L.V., C.F., C.L.M., P.M.), The University of Melbourne, Parkville; Centre of Excellence for Alzheimer's Disease Research and Care (S.M.L., T.P., S.R.-S., R.N.M.), Edith Cowan University, Joondalup, Australia; Department of Psychiatry (R.H.P.), Yale University School of Medicine, New Haven, CT; Academic Unit for Psychiatry of Old Age (D.A.), St. Vincent's Health, The University of Melbourne, Kew; National Ageing Research Institute (D.A.), Parkville, Australia; Department of Neurology (P.J.S.), Warren Alpert Medical School of Brown University, Providence, RI; Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship (O.S., P.B.), Australian e-Health Research Centre-BiaMedIA, Brisbane; Departments of Nuclear Medicine and Centre for PET (V.L.V., C.C.R.) and Medicine (V.L.V., C.C.R.), Austin Health, Heidelberg; Sir James McCusker Alzheimer's Disease Research Unit (S.M.L., T.P.), Hollywood Private Hospital, Perth; Co-operative Research Centre for Mental Health (S.M.L., T.P.), Carlton South; and CogState Ltd. (P.M.), Melbourne, Australia.
authors.forename: Tenielle
authors.initials: T
authors.lastname: Porter
authors.affiliation: From The Florey Institute of Neuroscience and Mental Health (Y.Y.L., V.L.V., C.F., C.L.M., P.M.), The University of Melbourne, Parkville; Centre of Excellence for Alzheimer's Disease Research and Care (S.M.L., T.P., S.R.-S., R.N.M.), Edith Cowan University, Joondalup, Australia; Department of Psychiatry (R.H.P.), Yale University School of Medicine, New Haven, CT; Academic Unit for Psychiatry of Old Age (D.A.), St. Vincent's Health, The University of Melbourne, Kew; National Ageing Research Institute (D.A.), Parkville, Australia; Department of Neurology (P.J.S.), Warren Alpert Medical School of Brown University, Providence, RI; Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship (O.S., P.B.), Australian e-Health Research Centre-BiaMedIA, Brisbane; Departments of Nuclear Medicine and Centre for PET (V.L.V., C.C.R.) and Medicine (V.L.V., C.C.R.), Austin Health, Heidelberg; Sir James McCusker Alzheimer's Disease Research Unit (S.M.L., T.P.), Hollywood Private Hospital, Perth; Co-operative Research Centre for Mental Health (S.M.L., T.P.), Carlton South; and CogState Ltd. (P.M.), Melbourne, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.affiliation: From The Florey Institute of Neuroscience and Mental Health (Y.Y.L., V.L.V., C.F., C.L.M., P.M.), The University of Melbourne, Parkville; Centre of Excellence for Alzheimer's Disease Research and Care (S.M.L., T.P., S.R.-S., R.N.M.), Edith Cowan University, Joondalup, Australia; Department of Psychiatry (R.H.P.), Yale University School of Medicine, New Haven, CT; Academic Unit for Psychiatry of Old Age (D.A.), St. Vincent's Health, The University of Melbourne, Kew; National Ageing Research Institute (D.A.), Parkville, Australia; Department of Neurology (P.J.S.), Warren Alpert Medical School of Brown University, Providence, RI; Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship (O.S., P.B.), Australian e-Health Research Centre-BiaMedIA, Brisbane; Departments of Nuclear Medicine and Centre for PET (V.L.V., C.C.R.) and Medicine (V.L.V., C.C.R.), Austin Health, Heidelberg; Sir James McCusker Alzheimer's Disease Research Unit (S.M.L., T.P.), Hollywood Private Hospital, Perth; Co-operative Research Centre for Mental Health (S.M.L., T.P.), Carlton South; and CogState Ltd. (P.M.), Melbourne, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Fowler
authors.affiliation: From The Florey Institute of Neuroscience and Mental Health (Y.Y.L., V.L.V., C.F., C.L.M., P.M.), The University of Melbourne, Parkville; Centre of Excellence for Alzheimer's Disease Research and Care (S.M.L., T.P., S.R.-S., R.N.M.), Edith Cowan University, Joondalup, Australia; Department of Psychiatry (R.H.P.), Yale University School of Medicine, New Haven, CT; Academic Unit for Psychiatry of Old Age (D.A.), St. Vincent's Health, The University of Melbourne, Kew; National Ageing Research Institute (D.A.), Parkville, Australia; Department of Neurology (P.J.S.), Warren Alpert Medical School of Brown University, Providence, RI; Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship (O.S., P.B.), Australian e-Health Research Centre-BiaMedIA, Brisbane; Departments of Nuclear Medicine and Centre for PET (V.L.V., C.C.R.) and Medicine (V.L.V., C.C.R.), Austin Health, Heidelberg; Sir James McCusker Alzheimer's Disease Research Unit (S.M.L., T.P.), Hollywood Private Hospital, Perth; Co-operative Research Centre for Mental Health (S.M.L., T.P.), Carlton South; and CogState Ltd. (P.M.), Melbourne, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Rainey-Smith
authors.affiliation: From The Florey Institute of Neuroscience and Mental Health (Y.Y.L., V.L.V., C.F., C.L.M., P.M.), The University of Melbourne, Parkville; Centre of Excellence for Alzheimer's Disease Research and Care (S.M.L., T.P., S.R.-S., R.N.M.), Edith Cowan University, Joondalup, Australia; Department of Psychiatry (R.H.P.), Yale University School of Medicine, New Haven, CT; Academic Unit for Psychiatry of Old Age (D.A.), St. Vincent's Health, The University of Melbourne, Kew; National Ageing Research Institute (D.A.), Parkville, Australia; Department of Neurology (P.J.S.), Warren Alpert Medical School of Brown University, Providence, RI; Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship (O.S., P.B.), Australian e-Health Research Centre-BiaMedIA, Brisbane; Departments of Nuclear Medicine and Centre for PET (V.L.V., C.C.R.) and Medicine (V.L.V., C.C.R.), Austin Health, Heidelberg; Sir James McCusker Alzheimer's Disease Research Unit (S.M.L., T.P.), Hollywood Private Hospital, Perth; Co-operative Research Centre for Mental Health (S.M.L., T.P.), Carlton South; and CogState Ltd. (P.M.), Melbourne, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Snyder
authors.affiliation: From The Florey Institute of Neuroscience and Mental Health (Y.Y.L., V.L.V., C.F., C.L.M., P.M.), The University of Melbourne, Parkville; Centre of Excellence for Alzheimer's Disease Research and Care (S.M.L., T.P., S.R.-S., R.N.M.), Edith Cowan University, Joondalup, Australia; Department of Psychiatry (R.H.P.), Yale University School of Medicine, New Haven, CT; Academic Unit for Psychiatry of Old Age (D.A.), St. Vincent's Health, The University of Melbourne, Kew; National Ageing Research Institute (D.A.), Parkville, Australia; Department of Neurology (P.J.S.), Warren Alpert Medical School of Brown University, Providence, RI; Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship (O.S., P.B.), Australian e-Health Research Centre-BiaMedIA, Brisbane; Departments of Nuclear Medicine and Centre for PET (V.L.V., C.C.R.) and Medicine (V.L.V., C.C.R.), Austin Health, Heidelberg; Sir James McCusker Alzheimer's Disease Research Unit (S.M.L., T.P.), Hollywood Private Hospital, Perth; Co-operative Research Centre for Mental Health (S.M.L., T.P.), Carlton South; and CogState Ltd. (P.M.), Melbourne, Australia.
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.affiliation: From The Florey Institute of Neuroscience and Mental Health (Y.Y.L., V.L.V., C.F., C.L.M., P.M.), The University of Melbourne, Parkville; Centre of Excellence for Alzheimer's Disease Research and Care (S.M.L., T.P., S.R.-S., R.N.M.), Edith Cowan University, Joondalup, Australia; Department of Psychiatry (R.H.P.), Yale University School of Medicine, New Haven, CT; Academic Unit for Psychiatry of Old Age (D.A.), St. Vincent's Health, The University of Melbourne, Kew; National Ageing Research Institute (D.A.), Parkville, Australia; Department of Neurology (P.J.S.), Warren Alpert Medical School of Brown University, Providence, RI; Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship (O.S., P.B.), Australian e-Health Research Centre-BiaMedIA, Brisbane; Departments of Nuclear Medicine and Centre for PET (V.L.V., C.C.R.) and Medicine (V.L.V., C.C.R.), Austin Health, Heidelberg; Sir James McCusker Alzheimer's Disease Research Unit (S.M.L., T.P.), Hollywood Private Hospital, Perth; Co-operative Research Centre for Mental Health (S.M.L., T.P.), Carlton South; and CogState Ltd. (P.M.), Melbourne, Australia.
authors.forename: Olivier
authors.initials: O
authors.lastname: Salvado
authors.affiliation: From The Florey Institute of Neuroscience and Mental Health (Y.Y.L., V.L.V., C.F., C.L.M., P.M.), The University of Melbourne, Parkville; Centre of Excellence for Alzheimer's Disease Research and Care (S.M.L., T.P., S.R.-S., R.N.M.), Edith Cowan University, Joondalup, Australia; Department of Psychiatry (R.H.P.), Yale University School of Medicine, New Haven, CT; Academic Unit for Psychiatry of Old Age (D.A.), St. Vincent's Health, The University of Melbourne, Kew; National Ageing Research Institute (D.A.), Parkville, Australia; Department of Neurology (P.J.S.), Warren Alpert Medical School of Brown University, Providence, RI; Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship (O.S., P.B.), Australian e-Health Research Centre-BiaMedIA, Brisbane; Departments of Nuclear Medicine and Centre for PET (V.L.V., C.C.R.) and Medicine (V.L.V., C.C.R.), Austin Health, Heidelberg; Sir James McCusker Alzheimer's Disease Research Unit (S.M.L., T.P.), Hollywood Private Hospital, Perth; Co-operative Research Centre for Mental Health (S.M.L., T.P.), Carlton South; and CogState Ltd. (P.M.), Melbourne, Australia.
authors.forename: Pierrick
authors.initials: P
authors.lastname: Bourgeat
authors.affiliation: From The Florey Institute of Neuroscience and Mental Health (Y.Y.L., V.L.V., C.F., C.L.M., P.M.), The University of Melbourne, Parkville; Centre of Excellence for Alzheimer's Disease Research and Care (S.M.L., T.P., S.R.-S., R.N.M.), Edith Cowan University, Joondalup, Australia; Department of Psychiatry (R.H.P.), Yale University School of Medicine, New Haven, CT; Academic Unit for Psychiatry of Old Age (D.A.), St. Vincent's Health, The University of Melbourne, Kew; National Ageing Research Institute (D.A.), Parkville, Australia; Department of Neurology (P.J.S.), Warren Alpert Medical School of Brown University, Providence, RI; Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship (O.S., P.B.), Australian e-Health Research Centre-BiaMedIA, Brisbane; Departments of Nuclear Medicine and Centre for PET (V.L.V., C.C.R.) and Medicine (V.L.V., C.C.R.), Austin Health, Heidelberg; Sir James McCusker Alzheimer's Disease Research Unit (S.M.L., T.P.), Hollywood Private Hospital, Perth; Co-operative Research Centre for Mental Health (S.M.L., T.P.), Carlton South; and CogState Ltd. (P.M.), Melbourne, Australia.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
authors.affiliation: From The Florey Institute of Neuroscience and Mental Health (Y.Y.L., V.L.V., C.F., C.L.M., P.M.), The University of Melbourne, Parkville; Centre of Excellence for Alzheimer's Disease Research and Care (S.M.L., T.P., S.R.-S., R.N.M.), Edith Cowan University, Joondalup, Australia; Department of Psychiatry (R.H.P.), Yale University School of Medicine, New Haven, CT; Academic Unit for Psychiatry of Old Age (D.A.), St. Vincent's Health, The University of Melbourne, Kew; National Ageing Research Institute (D.A.), Parkville, Australia; Department of Neurology (P.J.S.), Warren Alpert Medical School of Brown University, Providence, RI; Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship (O.S., P.B.), Australian e-Health Research Centre-BiaMedIA, Brisbane; Departments of Nuclear Medicine and Centre for PET (V.L.V., C.C.R.) and Medicine (V.L.V., C.C.R.), Austin Health, Heidelberg; Sir James McCusker Alzheimer's Disease Research Unit (S.M.L., T.P.), Hollywood Private Hospital, Perth; Co-operative Research Centre for Mental Health (S.M.L., T.P.), Carlton South; and CogState Ltd. (P.M.), Melbourne, Australia.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: From The Florey Institute of Neuroscience and Mental Health (Y.Y.L., V.L.V., C.F., C.L.M., P.M.), The University of Melbourne, Parkville; Centre of Excellence for Alzheimer's Disease Research and Care (S.M.L., T.P., S.R.-S., R.N.M.), Edith Cowan University, Joondalup, Australia; Department of Psychiatry (R.H.P.), Yale University School of Medicine, New Haven, CT; Academic Unit for Psychiatry of Old Age (D.A.), St. Vincent's Health, The University of Melbourne, Kew; National Ageing Research Institute (D.A.), Parkville, Australia; Department of Neurology (P.J.S.), Warren Alpert Medical School of Brown University, Providence, RI; Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship (O.S., P.B.), Australian e-Health Research Centre-BiaMedIA, Brisbane; Departments of Nuclear Medicine and Centre for PET (V.L.V., C.C.R.) and Medicine (V.L.V., C.C.R.), Austin Health, Heidelberg; Sir James McCusker Alzheimer's Disease Research Unit (S.M.L., T.P.), Hollywood Private Hospital, Perth; Co-operative Research Centre for Mental Health (S.M.L., T.P.), Carlton South; and CogState Ltd. (P.M.), Melbourne, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Maruff
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism / Q000523:psychology; D018450:Disease Progression; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000378:metabolism; D061212:Memory, Episodic; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D062706:Prodromal Symptoms
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4