Influence of Comorbidity of Cerebrovascular Disease and Amyloid-β on Alzheimer’s Disease

Article type: Research Article

Authors: Yassi, Nawaf^{a; b; c; *} | Hilal, Saima^{d; q} | Xia, Ying^e | Lim, Yen Ying^c | Watson, Rosie^{b; c; f} | Kuijf, Hugo^g | Fowler, Christopher^c | Yates, Paul^{h; r} | Maruff, Paulⁱ | Martins, Ralph^j | Ames, David^{k; l} | Chen, Christopher^d | Rowe, Christopher C.^{m; p} | Villemagne, Victor L.^m | Salvado, Olivierⁿ | Desmond, Patricia M.^o | Masters, Colin L.^c

Affiliations: [a] Departments of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia | [b] Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia | [c] Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia | [d] Memory Aging and Cognition Centre, Department of Pharmacology, National University of Singapore, Singapore | [e] The Australian e-Health Research Centre, Commonwealth Scientific and Industrial Research Organisation, Brisbane, Australia | [f] Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia | [g] Image Sciences Institute, University Medical Center, Utrecht, Utrecht, Netherlands | [h] Department of Aged Care Services, Austin Health, Heidelberg, Australia | [i] Cogstate Ltd, Melbourne, VIC, Australia | [j] Centre of Excellence for Alzheimer’s Disease Research and Care, Edith Cowan University, Perth, Australia | [k] Academic Unit for Psychiatry of Old Age, University of Melbourne, Parkville, Australia | [l] National Ageing Research Institute, Parkville, Australia | [m] Department of Molecular Imaging and Therapy, Austin Health, Heidelberg, Australia | [n] Data61, Commonwealth Scientific and Industrial Research Organisation, Brisbane, Australia | [o] Department of Radiology, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia | [p] Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia | [q] Saw Swee Hock School of Public Health, National University of Singapore, Singapore | [r] Department of Medicine, Austin Hospital, University of Melbourne, Heidelberg, Australia

Correspondence: [*] Correspondence to: Nawaf Yassi, PhD, Departments of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, 3050, Australia. E-mail: nawaf.yassi@unimelb.edu.au.

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.

Keywords: Alzheimer’s disease, cerebrovascular disease, magnetic resonance imaging, mild cognitive impairment, positron emission tomography, stroke

DOI: 10.3233/JAD-191028

Journal: Journal of Alzheimer's Disease, vol. 73, no. 3, pp. 897-907, 2020