title: Independent and Interactive Influences of the APOE Genotype and Beta-Amyloid Burden on Cognitive Function in Mild Cognitive Impairment.
abstract: This study aimed to investigate the independent and interactive influences of apolipoprotein E (APOE) ε4 and beta-amyloid (Aβ) on multiple cognitive domains in a large group of cognitively normal (CN) individuals and patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Participants were included if clinical and cognitive assessments, amyloid imaging, and APOE genotype were all available from the Alzheimer's Disease Neuroimaging Initiative database (CN = 324, MCI = 502, AD = 182). Individuals with one or two copies of ε4 were designated as APOE ε4 carriers (ε4+); individuals with no ε4 were designated as APOE ε4 non-carriers (ε4-). Based on mean florbetapir standard uptake value ratios, participants were classified as Aβ burden-positive (Aβ+) or Aβ burden-negative (Aβ-). In MCI, APOE ε4 effects were predominantly observed on frontal executive function, with ε4+ participants exhibiting poorer performances; Aβ positivity had no influence on this effect. Aβ effects were observed on global cognition, memory, and visuospatial ability, with Aβ+ participants exhibiting poorer performances. Measures of frontal executive function were not influenced by Aβ. Interactive effects of APOE ε4+ and Aβ were observed on global cognition and verbal recognition memory. Aβ, not APOE ε4+, influenced clinical severity and functional status. The influences of APOE ε4+ and Aβ on cognitive function were minimal in CN and AD. In conclusion, we provide further evidence of both independent and interactive influences of APOE ε4+ and Aβ on cognitive function in MCI, with APOE ε4+ and Aβ showing dissociable effects on executive and non-executive functions, respectively.
authors.affiliation: Premedical Science, College of Medicine, Chosun University, Gwangju, Korea.
authors.forename: Eun Hyun
authors.identifier: 0000-0002-4764-7464
authors.initials: EH
authors.lastname: Seo
authors.affiliation: Department of Neuropsychiatry, School of Medicine, Chosun University/Chosun University Hospital, Gwangju, Korea.
authors.forename: Sang Hoon
authors.identifier: 0000-0003-0098-070X
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Neuropsychiatry, School of Medicine, Chosun University/Chosun University Hospital, Gwangju, Korea.
authors.forename: Sang Hag
authors.identifier: 0000-0003-3222-1409
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Chosun University/Chosun University Hospital, Gwangju, Korea.
authors.forename: Seong-Ho
authors.identifier: 0000-0001-9420-6701
authors.initials: SH
authors.lastname: Kang
authors.affiliation: Department of Neuropsychiatry, School of Medicine, Chosun University/Chosun University Hospital, Gwangju, Korea.
authors.forename: Il Han
authors.identifier: 0000-0001-6547-9735
authors.initials: IH
authors.lastname: Choo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds / Q000737:chemistry; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging; D003071:Cognition; D060825:Cognitive Dysfunction / Q000235:genetics / Q000473:pathology*; D016208:Databases, Factual; D003710:Demography; D005026:Ethylene Glycols / Q000737:chemistry; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D011859:Radiography
chemical_list: D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D005026:Ethylene Glycols; C545186:florbetapir
keywords: APOE ε4+; Alzheimer Disease; Beta-amyloid Burden; Mild Cognitive Impairment; Neuropsychology
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