Subjective Memory Complaints in APOEɛ4 Carriers are Associated with High Amyloid-β Burden

Article type: Research Article

Authors: Zwan, Marissa D.^{a; b} | Villemagne, Victor L.^{b; c} | Doré, Vincent^d | Buckley, Rachel^{c; e} | Bourgeat, Pierrick^d | Veljanoski, Robyn^b | Salvado, Olivier^d | Williams, Rob^c | Margison, Laura^b | Rembach, Alan^c | Macaulay, S. Lance^f | Martins, Ralph^g | Ames, David^{h; i} | van der Flier, Wiesje M.^{a; j} | Ellis, Kathryn A.^{c; i} | Scheltens, Philip^a | Masters, Colin L.^c | Rowe, Christopher C.^{b; *} | for the AIBL study

Affiliations: [a] Department of Neurology and Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands | [b] Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia | [c] The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Victoria, Australia | [d] CSIRO Digital Productivity Flagship, The Australian e-Health Research Centre – BioMedIA, Herston, Queensland, Australia | [e] Melbourne School of Psychological Sciences, The University of Melbourne, Victoria, Australia | [f] CSIRO Food and Nutrion Flagship, Parkville, Victoria, Australia | [g] Centre of Excellence for Alzheimer’s Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia | [h] National Ageing Research Institute, Parkville, Victoria, Australia | [i] Department of Psychiatry, The University of Melbourne, Victoria, Australia | [j] Department of Epidemiology and Biostatistics, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands

Correspondence: [*] Correspondence to: Prof. Dr. Christopher C. Rowe, Department of Nuclear Medicine and Centre for PET, Austin Health, 145 Studley Road, Heidelberg, Victoria 3084, Australia. Tel.: +61 3 94965183; Fax: +61 3 9496 5663; E-mail: [email protected].

Abstract: Background:APOE ɛ4 genotype and aging have been identified as risk factors for Alzheimer’s disease (AD). In addition, subjective memory complaints (SMC) might be a first clinical expression of the effect of AD pathology on cognitive functioning. Objective:To assess whether APOE ɛ4 genotype, age, SMC, and episodic memory are risk factors for high amyloid-β (Aβ) burden in cognitively normal elderly. Methods:307 cognitively normal participants (72.7 ± 6.8 years, 53% female, 55% SMC) from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study underwent amyloid PET and APOE genotyping. Logistic regression analyses were performed to determine the association of APOE ɛ4 genotype, age, SMC, and episodic memory with Aβ pathology. Results:Odds of high Aβ burden were greater at an older age (OR = 3.21; 95% CI = 1.68–6.14), when SMC were present (OR = 1.90; 95% CI = 1.03–3.48), and for APOE ɛ4 carriers (OR = 7.49; 95% CI = 3.96–14.15), while episodic memory was not associated with odds of high Aβ burden. Stratified analyses showed that odds of SMC for high Aβ burden were increased in specifically APOE ɛ4 carriers (OR = 4.58, 95% CI = 1.83–11.49) and younger participants (OR = 3.73, 95% CI = 1.39–10.01). Conclusion:Aging, APOE ɛ4 genotype, and SMC were associated with high Aβ burden. SMC were especially indicative of high Aβ burden in younger participants and in APOE ɛ4 carriers. These findings suggest that selection based on the presence of SMC, APOE ɛ4 genotype and age may help identify healthy elderly participants with high Aβ burden eligible for secondary prevention trials.

Keywords: Aging, amyloid-β, apolipoprotein E, [¹¹C]-PiB, episodic memory, [¹⁸F]flutemetamol, positron emission tomography

DOI: 10.3233/JAD-150446

Journal: Journal of Alzheimer's Disease, vol. 49, no. 4, pp. 1115-1122, 2016