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Title: | APOEɛ4 Genotype, Amyloid, and Clinical Disease Progression in Cognitively Normal Older Adults. |
Authors: | Hollands, Simone;Lim, Yen Ying;Laws, Simon M;Villemagne, Victor L;Pietrzak, Robert H;Harrington, Karra;Porter, Tenielle;Snyder, Peter;Ames, David;Fowler, Christopher;Rainey-Smith, Stephanie R;Martins, Ralph N;Salvado, Olivier;Robertson, Joanne;Rowe, Christopher C;Masters, Colin L;Maruff, Paul |
Affiliation: | La Trobe University, Melbourne, VIC, Australia Cogstate Ltd., Melbourne, VIC, Australia Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, WA, Australia Co-operative Research Centre for Mental Health, http://www.mentalhealthcrc.com The Florey Institute, The University of Melbourne, Parkville, VIC, Australia Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, VIC, Australia Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI, USA Academic Unit for Psychiatry of Old Age, St. Vincent's Health, The University of Melbourne, Kew, VIC, Australia National Ageing Research Institute, Parkville, VIC, Australia Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship, Australian e-Health Research Centre-BiaMedIA, Brisbane, QLD, Australia |
Issue Date: | 2017 |
Citation: | Journal of Alzheimer's disease : JAD 2017; 57(2): 411-422 |
Abstract: | In cognitively normal (CN) older adults, carriage of the apolipoprotein E (APOE) ɛ4 allele is associated with increased risk for dementia of the Alzheimer type (AD-dementia). It is unclear whether this occurs solely through APOEɛ4 increasing amyloid-β (Aβ) accumulation or through processes independent of Aβ. To determine the extent and nature to which APOEɛ4 increases risk for clinical disease progression in CN older adults. Data from the total (n = 765) and Aβ-imaged (n = 423) CN cohort in the Australian Imaging, Biomarker and Lifestyle (AIBL) Study of Ageing was analyzed using Cox proportional hazard models to estimate ɛ4 risk for clinical disease progression over a 72-month follow-up. With Aβ status unknown and risk from demographic characteristics controlled, ɛ4 carriage increased risk for clinical disease progression over 72 months by 2.66 times compared to risk of non-ɛ4 carriage. Re-analysis with Aβ status included showed that abnormally high Aβ increased risk for clinical disease progression over 72 months by 2.11 times compared to risk of low Aβ. However, with Aβ level known, ɛ4 carriage was no longer predictive of clinical disease progression. In CN older adults, the risk of ɛ4 for clinical disease progression occurs through the effect of ɛ4 increasing Aβ levels. |
URI: | http://ahro.austin.org.au/austinjspui/handle/1/17806 |
DOI: | 10.3233/JAD-161019 |
ORCID: | 0000-0003-3910-2453 |
PubMed URL: | 28234254 |
Type: | Journal Article |
Subjects: | Alzheimer type dementia Alzheimer’s disease amyloid-β apolipoprotein E4 positron emission tomography |
Appears in Collections: | Journal articles |
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