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

Nawaf Yassi, Saima Hilal, Ying Xia, Yen Ying Lim, Rosie Watson, Hugo Kuijf, Christopher Fowler, Paul Yates, Paul Maruff, Ralph Martins, David Ames, Christopher Chen, Christopher C. Rowe, Victor L. Villemagne, Olivier Salvado, Patricia M. Desmond, Colin L. Masters

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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.

Original languageEnglish
Pages (from-to)897-907
Number of pages11
JournalJournal of Alzheimer's Disease
Issue number3
Publication statusPublished - 4 Feb 2020
Externally publishedYes


  • Alzheimer’s disease
  • cerebrovascular disease
  • magnetic resonance imaging
  • mild cognitive impairment
  • positron emission tomography
  • stroke
  • Influence of Comorbidity of Cerebrovascular Disease and Amyloid-on Alzheimer's Disease

    Yassi, N., Hilal, S., Xia, Y., Lim, Y. Y., Watson, R., Kuijf, H., Fowler, C., Yates, P., Maruff, P., Martins, R., Ames, D., Chen, C., Rowe, C. C., Villemagne, V. L., Salvado, O., Desmond, P. M. & Masters, C. L., 2024, Handbook of Prevention and Alzheimer’s Disease. IOS Press, Vol. 10. p. 381-394 14 p. (Advances in Alzheimer's Disease; vol. 10).

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