Abstract
The AT(N) research framework was introduced in 2018 to define Alzheimer's disease as a biological entity. It is recognized that Alzheimer's disease lesions rarely occur in isolation in older brains, with cerebrovascular disease (CVD) being a common comorbidity. To fully characterize the disorder of dementia, the AT(N) framework needs to be extended with biomarkers for other disorders. The present review examines some of the requirements for adding a 'V' to the AT(N), and examines the currently available biomarkers as definitive markers of CVD. Neuroimaging biomarkers of CVD have received the greatest attention, with rapid advances in MRI techniques showing the greatest promise. Challenges remain in standardization of techniques, validation of some of the results and assessing total CVD burden from diverse lesion types. Retinal imaging shows promise as a window to cerebral vasculature. Biochemical markers are advancing rapidly, but their specificity for CVD is not established. Biomarkers of CVD have seen rapid advances but further validation and determination of their specificity are needed before they can be reliably used to delineate a V in the AT(N) framework as definitive indicators of significant CVD.
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