Christa Dang1,2, Karra D Harrington2,3, Yen Ying Lim2, David Ames4,5, Jason Hassenstab6,7,8, Simon M Laws3,9,10, Nawaf Yassi2,11, Martha Hickey1, Stephanie R Rainey-Smith12,13, Joanne Robertson2, Christopher C Rowe14,15, Hamid R Sohrabi12,16, Olivier Salvado17, Michael Weinborn12,13,18, Victor L Villemagne2,14,15, Colin L Masters2, Paul Maruff2,19. 1. Department of Obstetrics and Gynaecology, Melbourne Medical School, The University of Melbourne, Parkville, Victoria, Australia. 2. The Florey Institute, The University of Melbourne, Parkville, Victoria, Australia. 3. Cooperative Research Centre for Mental Health, Parkville, Victoria, Australia. 4. Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia. 5. National Ageing Research Institute, Parkville, Victoria, Australia. 6. Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA. 7. Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA. 8. Department of Psychological & Brain Sciences, Washington University, St. Louis, MO, USA. 9. Collaborative Genomics Group, Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia. 10. School of Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Western Australia, Australia. 11. Department of Medicine and Neurology, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia. 12. Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia. 13. Australian Alzheimer's Research Foundation, Ralph and Patricia Sarich Neuroscience Research Institute, Nedlands, Western Australia, Australia. 14. Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Victoria, Australia. 15. Department of Medicine, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia. 16. Department of Biomedical Sciences, Macquarie University, Sydney, Australia. 17. CSIRO Health and Biosecurity, the Australian eHealth Research Centre, Brisbane, Queensland, Australia. 18. School of Psychological Science, University of Western Australia, Crawley, Western Australia, Australia. 19. CogState Ltd., Melbourne, Victoria, Australia.
Abstract
OBJECTIVE: To prospectively examine 8-year risk of clinical disease progression to mild cognitive impairment (MCI)/dementia in older adults ≥60 with superior episodic memory (SuperAgers) compared to those cognitively normal for their age (CNFA). Additionally, to determine the extent to which SuperAgers were resilient to the negative effects of elevated amyloid-beta (Aβ+) on cognition. METHOD: Participants were classified as SuperAgers based on episodic memory performance consistent with younger adults aged 30-44 and no impairment on non-memory tests (n = 179), and were matched with CNFA on age, sex, education, and follow-up time (n = 179). Subdistribution hazard models examined risk of clinical progression to MCI/dementia. Linear mixed models assessed the effect of Aβ on cognition over time. RESULTS: Prevalence of Aβ+ and APOE ε4 was equivalent between SuperAgers and CNFA. SuperAgers had 69%-73% reduced risk of clinical progression to MCI/dementia compared to CNFA (HR: 0.27-0.31, 95% CI: 0.11-0.73, p < .001). Aβ+ was associated with cognitive decline in verbal memory and executive function, regardless of SuperAger/CNFA classification. In the absence of Aβ+, equivalent age-related changes in cognition were observed between SuperAgers and CNFA. CONCLUSIONS: SuperAgers displayed resilience against clinical progression to MCI/dementia compared to CNFA despite equivalent risk for Alzheimer's disease (AD); however, SuperAgers had no greater protection from Aβ+ than CNFA. The deleterious effects of Aβ on cognition persist regardless of baseline cognitive ability. Thus, superior cognitive performance does not reflect resistance against the neuropathological processes associated with AD, and the observed resilience for SuperAgers may instead reflect neuropsychological criteria for cognitive impairment.
OBJECTIVE: To prospectively examine 8-year risk of clinical disease progression to mild cognitive impairment (MCI)/dementia in older adults ≥60 with superior episodic memory (SuperAgers) compared to those cognitively normal for their age (CNFA). Additionally, to determine the extent to which SuperAgers were resilient to the negative effects of elevated amyloid-beta (Aβ+) on cognition. METHOD:Participants were classified as SuperAgers based on episodic memory performance consistent with younger adults aged 30-44 and no impairment on non-memory tests (n = 179), and were matched with CNFA on age, sex, education, and follow-up time (n = 179). Subdistribution hazard models examined risk of clinical progression to MCI/dementia. Linear mixed models assessed the effect of Aβ on cognition over time. RESULTS: Prevalence of Aβ+ and APOE ε4 was equivalent between SuperAgers and CNFA. SuperAgers had 69%-73% reduced risk of clinical progression to MCI/dementia compared to CNFA (HR: 0.27-0.31, 95% CI: 0.11-0.73, p < .001). Aβ+ was associated with cognitive decline in verbal memory and executive function, regardless of SuperAger/CNFA classification. In the absence of Aβ+, equivalent age-related changes in cognition were observed between SuperAgers and CNFA. CONCLUSIONS: SuperAgers displayed resilience against clinical progression to MCI/dementia compared to CNFA despite equivalent risk for Alzheimer's disease (AD); however, SuperAgers had no greater protection from Aβ+ than CNFA. The deleterious effects of Aβ on cognition persist regardless of baseline cognitive ability. Thus, superior cognitive performance does not reflect resistance against the neuropathological processes associated with AD, and the observed resilience for SuperAgers may instead reflect neuropsychological criteria for cognitive impairment.
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Authors: Christa Dang; Nawaf Yassi; Karra D Harrington; Ying Xia; Yen Ying Lim; David Ames; Simon M Laws; Martha Hickey; Stephanie Rainey-Smith; Hamid R Sohrabi; James D Doecke; Jurgen Fripp; Olivier Salvado; Peter J Snyder; Michael Weinborn; Victor L Villemagne; Christopher C Rowe; Colin L Masters; Paul Maruff Journal: Alzheimers Dement (Amst) Date: 2019-08-12