title: Longitudinal cognitive decline in the AIBL cohort: The role of APOE ε4 status.
abstract: The ε4 polymorphism of the APOE gene confers a substantially increased risk of developing Alzheimer's disease. However, the influence of the ε4 allele on age-related cognitive functioning is more contentious. Previously, we demonstrated relatively little evidence for a role of the ε4 allele on baseline cognitive performance in older adults in the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing (Foster et al., 2013). We here investigated whether the APOE ε4 allele influenced cognitive status over time when the AIBL cohort was studied longitudinally over a 3-year period. The AIBL neuropsychological test battery was administered at baseline, after 18 months and again after 36 months. Participants comprised 764 Healthy Controls and 131 Mild Cognitively Impaired individuals enrolled in the AIBL Study of Ageing. We compared individuals within each group with and without an ε4 allele. Healthy Controls with an ε4 allele manifested a modest acceleration in cognitive decline over 36 months on measures of verbal episodic memory. By contrast, Mild Cognitively Impaired individuals with an ε4 allele showed increased cognitive decline across a range of cognitive tasks, putatively reflecting early cognitive signs of Alzheimer's disease. Given the long prodromal period that has been noted in late onset Alzheimer's disease, we suggest that these findings are consistent with a prodromal account rather than a phenotypic account of ε4-related cognitive ageing.
authors.affiliation: School of Psychology and Speech Pathology, Curtin University, Perth, Western Australia, Australia; School of Public Health, Curtin University, Perth, Western Australia, Australia; Maryland Psychiatric Research Center, School of Medicine, University of Maryland, MD, United States.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Albrecht
authors.affiliation: National Ageing Research Institute, Royal Melbourne Hospital, Victoria, Australia; CSIRO, Parkville, Victoria, Australia.
authors.forename: Cassandra
authors.initials: C
authors.lastname: Szoeke
authors.affiliation: Cogstate Ltd, Melbourne, Victoria, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Maruff
authors.affiliation: Department of Psychology and ARC Centre of Excellence in Cognition and its Disorders, Macquarie University, Sydney, Australia.
authors.forename: Greg
authors.initials: G
authors.lastname: Savage
authors.affiliation: Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, St. Vincent's Aged Psychiatry Service, St George's Hospital, Victoria, Australia; School of Psychiatry and Clinical Neurosciences and Western Australia Centre for Health and Ageing, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Nicola T
authors.initials: NT
authors.lastname: Lautenschlager
authors.affiliation: National Ageing Research Institute, Royal Melbourne Hospital, Victoria, Australia; Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, St. Vincent's Aged Psychiatry Service, St George's Hospital, Victoria, Australia; Mental Health Research Institute, The University of Melbourne, 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, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia; Sir James McCusker Alzheimer's Research Unit, Hollywood Private Hospital, Perth, Western Australia, Australia.
authors.forename: Kevin
authors.initials: K
authors.lastname: Taddei
authors.affiliation: Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia; Sir James McCusker Alzheimer's Research Unit, Hollywood Private Hospital, Perth, Western Australia, Australia.
authors.forename: Ralph
authors.initials: R
authors.lastname: Martins
authors.affiliation: Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: National Ageing Research Institute, Royal Melbourne Hospital, Victoria, Australia; Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, St. Vincent's Aged Psychiatry Service, St George's Hospital, Victoria, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.affiliation: School of Psychology and Speech Pathology, Curtin University, Perth, Western Australia, Australia; Neurosciences Unit, Health Department of WA, Perth, Western Australia, Australia. Electronic address: j.foster@curtin.edu.au.
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Foster
mesh_terms: D000368:Aged; D053327:Apolipoprotein E4 / Q000235:genetics*; D000066492:Cognitive Aging; D060825:Cognitive Dysfunction / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests
chemical_list: D053327:Apolipoprotein E4
keywords: Ageing; Alzheimer's disease; Apolipoprotein ε4; Bayesian; Longitudinal; Mild cognitive impairment; Neuropsychological performance