Visual Memory Deficits in Middle-Aged APOEɛ4 Homozygotes Detected Using Unsupervised Cognitive Assessments

Article type: Research Article

Authors: Lim, Yen Ying^{a; *} | Pase, Matthew P.^{a; b} | Buckley, Rachel F.^{c; d; e} | Yassi, Nawaf^{f; g} | Bransby, Lisa^a | Fowler, Christopher^h | Laws, Simon M.^{i; j} | Masters, Colin L.^h | Maruff, Paul^{h; k}

Affiliations: [a] Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia | [b] Harvard T.H. Chan School of Public Health, Boston, MA, USA | [c] Melbourne School of Psychological Sciences, University of Melbourne, Parkville, Victoria, Australia | [d] Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA | [e] Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women’s Hospital, Boston, MA, USA | [f] Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia | [g] Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia | [h] Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia | [i] Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia | [j] School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, Western Australia, Australia | [k] Cogstate Ltd., Melbourne, Victoria, Australia

Correspondence: [*] Correspondence to: Yen Ying Lim, Turner Institute for Brain and Mental Health, 18 Innovation Walk, Clayton, VIC 3168, Australia. Tel.: +61 3 9035 6686; E-mail: yenying.lim@monash.edu.

Abstract: Background:The apolipoprotein E (APOE) ɛ4 allele is associated with dose-response effects on cognitive dysfunction and dementia risk in older adults. However, its effects on cognition in middle-aged adults remains unclear. Objective:We examined effects of ɛ4 heterozygosity and homozygosity on objective and subjective cognition in middle-aged adults enrolled in the Healthy Brain Project (HBP) and in older adults from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Methods:HBP participants (1,000 non-carriers; 450 ɛ4 heterozygotes; 50 ɛ4 homozygotes) completed unsupervised assessments of the Cogstate Brief Battery (CBB), ratings of subjective cognitive function and provided a saliva sample. AIBL cognitively normal participants (650 non-carriers; 204 ɛ4 heterozygotes; 31 ɛ4 homozygotes) completed in-person assessments of the CBB, ratings of subjective cognitive function and provided a blood sample. Results:Greater memory impairment was observed in middle-aged ɛ4 homozygotes compared with ɛ4 heterozygotes and non-carriers. When data from middle-aged (HBP) and older (AIBL) adults were pooled, the effect of ɛ4 homozygosity and memory impairment increased with age. In both middle-aged and older adults, ɛ4 heterozygotes did not differ from non-carriers on any measure of objective or subjective cognition. Conclusion:Memory impairment in ɛ4 homozygotes is evident in adults aged 50-60 years, and this can be detected through unsupervised cognitive assessments. The effect of ɛ4 homozygosity increases with older age. APOE ɛ4 homozygosity has a negative impact on memory as early as midlife, but due to the subtle magnitude of effect, our findings support the necessity of online platforms in large cohorts to assess these complex relationships.

Keywords: Alzheimer’s disease, apolipoprotein E, early detection, memory

DOI: 10.3233/JAD-201281

Journal: Journal of Alzheimer's Disease, vol. 79, no. 4, pp. 1563-1573, 2021