Nawaf Yassi1,2,3, Saima Hilal4,5, Ying Xia6, Yen Ying Lim3, Rosie Watson2,3,7, Hugo Kuijf8, Christopher Fowler3, Paul Yates9,10, Paul Maruff11, Ralph Martins12, David Ames13,14, Christopher Chen4, Christopher C Rowe15,16, Victor L Villemagne15, Olivier Salvado17, Patricia M Desmond18, Colin L Masters3. 1. Departments of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia. 2. Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia. 3. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia. 4. Memory Aging and Cognition Centre, Department of Pharmacology, National University of Singapore, Singapore. 5. Saw Swee Hock School of Public Health, National University of Singapore, Singapore. 6. The Australian e-Health Research Centre, Commonwealth Scientific and Industrial Research Organisation, Brisbane, Australia. 7. Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia. 8. Image Sciences Institute, University Medical Center, Utrecht, Utrecht, Netherlands. 9. Department of Aged Care Services, Austin Health, Heidelberg, Australia. 10. Department of Medicine, Austin Hospital, University of Melbourne, Heidelberg, Australia. 11. Cogstate Ltd, Melbourne, VIC, Australia. 12. Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Perth, Australia. 13. Academic Unit for Psychiatry of Old Age, University of Melbourne, Parkville, Australia. 14. National Ageing Research Institute, Parkville, Australia. 15. Department of Molecular Imaging and Therapy, Austin Health, Heidelberg, Australia. 16. Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia. 17. Data61, Commonwealth Scientific and Industrial Research Organisation, Brisbane, Australia. 18. Department of Radiology, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.
Abstract
BACKGROUND: Quantifying the contribution of cerebrovascular disease to the clinical and pathological profile of Alzheimer's disease is challenging. OBJECTIVE: We aimed to determine the influence of cerebrovascular disease, amyloid-β (Aβ), and their comorbidity on cognitive decline, hippocampal atrophy, and Aβ deposition, by evaluating data from the Australian Imaging, Biomarker and Lifestyle Study of Ageing. METHODS: Two-hundred and eighteen participants underwent Aβ PET, MRI, and cognitive assessment at 18-month intervals for up to 90 months. Aβ status was determined on baseline PET. Participants were also classified as V+ on baseline MRI if they had≥1 large cortical infarcts, subcortical infarcts, or cortical cerebral microinfarcts; or white matter hyperintensity volume greater than the 90th percentile of healthy controls. Linear mixed models were conducted comparing slopes of change in cognition, hippocampal volume, and Aβ load between the four resultant groups. RESULTS: Mean age at baseline was 74 years (range 59-96). One-hundred and fifteen participants were cognitively normal, 54 had mild cognitive impairment, and 49 had Alzheimer's disease. Compared to the Aβ-/V- group, the Aβ+/V- and Aβ+/V+ groups showed significantly faster cognitive decline and hippocampal atrophy over 90 months. V+ status was associated with greater cognitive decline (Cohen's d = 0.85, p < 0.001) and hippocampal atrophy (d = 2.05, p < 0.001) in the Aβ+ group but not in the Aβ- group. V+ status was not associated with Aβ accumulation in any group. CONCLUSION: Comorbidity of cerebrovascular disease and Aβ was associated with cognitive decline and neurodegeneration. Cerebrovascular disease was not associated with the rate of Aβ accumulation.
BACKGROUND: Quantifying the contribution of cerebrovascular disease to the clinical and pathological profile of Alzheimer's disease is challenging. OBJECTIVE: We aimed to determine the influence of cerebrovascular disease, amyloid-β (Aβ), and their comorbidity on cognitive decline, hippocampal atrophy, and Aβ deposition, by evaluating data from the Australian Imaging, Biomarker and Lifestyle Study of Ageing. METHODS: Two-hundred and eighteen participants underwent Aβ PET, MRI, and cognitive assessment at 18-month intervals for up to 90 months. Aβ status was determined on baseline PET. Participants were also classified as V+ on baseline MRI if they had≥1 large cortical infarcts, subcortical infarcts, or cortical cerebral microinfarcts; or white matter hyperintensity volume greater than the 90th percentile of healthy controls. Linear mixed models were conducted comparing slopes of change in cognition, hippocampal volume, and Aβ load between the four resultant groups. RESULTS: Mean age at baseline was 74 years (range 59-96). One-hundred and fifteen participants were cognitively normal, 54 had mild cognitive impairment, and 49 had Alzheimer's disease. Compared to the Aβ-/V- group, the Aβ+/V- and Aβ+/V+ groups showed significantly faster cognitive decline and hippocampal atrophy over 90 months. V+ status was associated with greater cognitive decline (Cohen's d = 0.85, p < 0.001) and hippocampal atrophy (d = 2.05, p < 0.001) in the Aβ+ group but not in the Aβ- group. V+ status was not associated with Aβ accumulation in any group. CONCLUSION:Comorbidity of cerebrovascular disease and Aβ was associated with cognitive decline and neurodegeneration. Cerebrovascular disease was not associated with the rate of Aβ accumulation.
Authors: Emily Rosenich; Lisa Bransby; Nawaf Yassi; Jurgen Fripp; Simon M Laws; Ralph N Martins; Christopher Fowler; Stephanie R Rainey-Smith; Christopher C Rowe; Colin L Masters; Paul Maruff; Yen Ying Lim Journal: Neurology Date: 2022-02-15 Impact factor: 11.800
Authors: Sonja M Kagerer; Clemens Schroeder; Jiri M G van Bergen; Simon J Schreiner; Rafael Meyer; Stefanie C Steininger; Laetitia Vionnet; Anton F Gietl; Valerie Treyer; Alfred Buck; Klaas P Pruessmann; Christoph Hock; Paul G Unschuld Journal: Front Aging Neurosci Date: 2022-03-03 Impact factor: 5.750
Authors: Christopher Fowler; Stephanie R Rainey-Smith; Sabine Bird; Julia Bomke; Pierrick Bourgeat; Belinda M Brown; Samantha C Burnham; Ashley I Bush; Carolyn Chadunow; Steven Collins; James Doecke; Vincent Doré; Kathryn A Ellis; Lis Evered; Amir Fazlollahi; Jurgen Fripp; Samantha L Gardener; Simon Gibson; Robert Grenfell; Elise Harrison; Richard Head; Liang Jin; Adrian Kamer; Fiona Lamb; Nicola T Lautenschlager; Simon M Laws; Qiao-Xin Li; Lucy Lim; Yen Ying Lim; Andrea Louey; S Lance Macaulay; Lucy Mackintosh; Ralph N Martins; Paul Maruff; Colin L Masters; Simon McBride; Lidija Milicic; Madeline Peretti; Kelly Pertile; Tenielle Porter; Morgan Radler; Alan Rembach; Joanne Robertson; Mark Rodrigues; Christopher C Rowe; Rebecca Rumble; Olivier Salvado; Greg Savage; Brendan Silbert; Magdalene Soh; Hamid R Sohrabi; Kevin Taddei; Tania Taddei; Christine Thai; Brett Trounson; Regan Tyrrell; Michael Vacher; Shiji Varghese; Victor L Villemagne; Michael Weinborn; Michael Woodward; Ying Xia; David Ames Journal: J Alzheimers Dis Rep Date: 2021-06-03
Authors: Xin Ying Chua; Yuek Ling Chai; Wee Siong Chew; Joyce R Chong; Hui Li Ang; Ping Xiang; Kaddy Camara; Amy R Howell; Federico Torta; Markus R Wenk; Saima Hilal; Narayanaswamy Venketasubramanian; Christopher P Chen; Deron R Herr; Mitchell K P Lai Journal: Alzheimers Res Ther Date: 2020-09-30 Impact factor: 6.982