Comorbidity of Cerebrovascular and Alzheimer’s Disease in Aging

Article type: Research Article

Authors: Xia, Ying^{a; †; *} | Yassi, Nawaf^{b; c; d; †} | Raniga, Parnesh^a | Bourgeat, Pierrick^a | Desmond, Patricia^e | Doecke, James^a | Ames, David^{f; g} | Laws, Simon M.^{h; i; j} | Fowler, Christopher^d | Rainey-Smith, Stephanie R.^{h; j} | Martins, Ralph^{h; j} | Maruff, Paul^{d; k} | Villemagne, Victor L.^{d; l; m} | Masters, Colin L.^d | Rowe, Christopher C.^{l; m} | Fripp, Jurgen^a | Salvado, Olivier^{a; n} | for the AIBL Research Group

Affiliations: [a] The Australian e-Health Research Centre, CSIRO Health and Biosecurity, Brisbane, QLD, Australia | [b] Department of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia | [c] Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia | [d] The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia | [e] Department of Radiology, The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia | [f] National Ageing Research Institute, Parkville, VIC, Australia | [g] Academic Unit for Psychiatry of Old Age, University of Melbourne, Parkville, VIC, Australia | [h] Centre of Excellence for Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia | [i] School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, Western Australia, WA, Australia | [j] Sir James McCusker Alzheimer’s Disease Research Unit, Hollywood Private Hospital, Perth, WA, Australia | [k] Cog State Ltd, Melbourne, VIC, Australia | [l] Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia | [m] Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia | [n] CSIRO Data61, Brisbane, QLD, Australia

Correspondence: [*] Correspondence to: Ying Xia, Level 5 UQ Health Sciences Building, Royal Brisbane and Women’s Hospital, Herston, Queensland 4029, Australia. E-mail: ying.xia@csiro.au.

Note: [†] These authors contributed equally to this work.

Abstract: Background:Cerebrovascular disease often coexists with Alzheimer’s disease (AD). While both diseases share common risk factors, their interrelationship remains unclear. Increasing the understanding of how cerebrovascular changes interact with AD is essential to develop therapeutic strategies and refine biomarkers for early diagnosis. Objective:We investigate the prevalence and risk factors for the comorbidity of amyloid-β (Aβ) and cerebrovascular disease in the Australian Imaging, Biomarkers and Lifestyle Study of Ageing, and further examine their cross-sectional association. Methods:A total of 598 participants (422 cognitively normal, 89 with mild cognitive impairment, 87 with AD) underwent positron emission tomography and structural magnetic resonance imaging for assessment of Aβ deposition and cerebrovascular disease. Individuals were categorized based on the comorbidity status of Aβ and cerebrovascular disease (V) as Aβ–V–, Aβ–V+, Aβ+V–, or Aβ+V+. Results:Advancing age was associated with greater likelihood of cerebrovascular disease, high Aβ load and their comorbidity. Apolipoprotein E ɛ4 carriage was only associated with Aβ positivity. Greater total and regional WMH burden were observed in participants with AD. However, no association were observed between Aβ and WMH measures after stratification by clinical classification, suggesting that the observed association between AD and cerebrovascular disease was driven by the common risk factor of age. Conclusion:Our observations demonstrate common comorbid condition of Aβ and cerebrovascular disease in later life. While our study did not demonstrate a convincing cross-sectional association between Aβ and WMH burden, future longitudinal studies are required to further confirm this.

Keywords: Alzheimer’s disease, amyloid, cerebrovascular disease, white matter hyperintensities

DOI: 10.3233/JAD-200419

Journal: Journal of Alzheimer's Disease, vol. 78, no. 1, pp. 321-334, 2020