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Developing robust biomarkers for vascular cognitive disorders: adding 'V' to the AT(N) research framework
1Centre for Healthy Brain Ageing, University of New South Wales and the Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, Australia.
Insights
Biomarkers for cerebrovascular disease (CVD) are advancing, particularly neuroimaging techniques. However, further validation and specificity testing are crucial before integrating CVD markers into the AT(N) framework for Alzheimer's disease research.
Area of Science:
- Neurology
- Biomarker Research
- Neurodegenerative Diseases
Background:
- The AT(N) framework defines Alzheimer's disease biologically.
- Cerebrovascular disease (CVD) frequently co-occurs with Alzheimer's lesions.
- The AT(N) framework requires extension with biomarkers for comorbidities like CVD.
Purpose of the Study:
- To review requirements for adding a 'V' (for CVD) to the AT(N) framework.
- To examine current biomarkers for definitive CVD detection.
Main Methods:
- Review of existing literature on CVD biomarkers.
- Focus on neuroimaging and biochemical markers.
- Assessment of biomarker standardization and validation.
Main Results:
- Neuroimaging MRI techniques show significant promise for CVD biomarker detection.
- Challenges include technique standardization, result validation, and assessing total CVD burden.
- Retinal imaging offers a potential view of cerebral vasculature; biochemical markers lack established CVD specificity.
Conclusions:
- CVD biomarkers have advanced rapidly.
- Further validation and specificity determination are necessary.
- Reliable CVD biomarkers are needed to establish the 'V' in the AT(N) framework.
Purpose Of Review:
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.
Recent Findings:
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.
Summary:
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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