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Biochemical markers in vascular cognitive impairment associated with subcortical small vessel disease - A consensus
A Wallin1,2, E Kapaki3, M Boban4
1Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. anders.wallin@neuro.gu.se.
Insights
Biochemical markers in vascular cognitive impairment due to small vessel disease (VCI-SSVD) show promise for differentiating it from Alzheimer's disease (AD). These markers, linked to blood-brain barrier disruption and inflammation, could aid clinical trials for both conditions.
Area of Science:
- Neurology
- Biochemistry
- Biomarker Discovery
Background:
- Vascular cognitive impairment (VCI) is a diverse condition linked to vascular disease.
- Subcortical small vessel disease (SSVD) is a significant and emerging subtype of VCI.
- Identifying biomarkers for VCI-SSVD is crucial for therapeutic development.
Purpose of the Study:
- To review the current evidence on biochemical markers for VCI-SSVD.
- To identify promising biomarkers for differentiating VCI-SSVD from Alzheimer's disease (AD).
Main Methods:
- Comprehensive literature search of Medline, PubMed, and Embase databases up to January 15, 2017.
- Expert review and iterative discussion of findings to finalize the review.
Main Results:
- Numerous CSF and blood biochemical markers identified for VCI-SSVD.
- Promising biomarkers linked to SSVD pathophysiology include CSF/blood albumin ratio, matrix metalloproteinases, neurofilament, and inflammatory cytokines.
- These markers differ from the characteristic CSF profile in AD (amyloid beta, tau).
Conclusions:
- Biochemical markers can help distinguish VCI-SSVD from AD.
- Combining VCI-SSVD and AD biomarkers may improve patient selection for clinical trials.
- Biomarker advancements could accelerate therapeutic progress in both VCI-SSVD and AD.
Background:
Vascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologies, all linked to underlying vascular disease. Among these, VCI related to subcortical small vessel disease (SSVD) is emerging as a major homogeneous subtype. Its progressive course raises the need for biomarker identification and/or development for adequate therapeutic interventions to be tested. In order to shed light in the current status on biochemical markers for VCI-SSVD, experts in field reviewed the recent evidence and literature data.
Method:
The group conducted a comprehensive search on Medline, PubMed and Embase databases for studies published until 15.01.2017. The proposal on current status of biochemical markers in VCI-SSVD was reviewed by all co-authors and the draft was repeatedly circulated and discussed before it was finalized.
Results:
This review identifies a large number of biochemical markers derived from CSF and blood. There is a considerable overlap of VCI-SSVD clinical symptoms with those of Alzheimer's disease (AD). Although most of the published studies are small and their findings remain to be replicated in larger cohorts, several biomarkers have shown promise in separating VCI-SSVD from AD. These promising biomarkers are closely linked to underlying SSVD pathophysiology, namely disruption of blood-CSF and blood-brain barriers (BCB-BBB) and breakdown of white matter myelinated fibres and extracellular matrix, as well as blood and brain inflammation. The leading biomarker candidates are: elevated CSF/blood albumin ratio, which reflects BCB/BBB disruption; altered CSF matrix metalloproteinases, reflecting extracellular matrix breakdown; CSF neurofilment as a marker of axonal damage, and possibly blood inflammatory cytokines and adhesion molecules. The suggested SSVD biomarker deviations contrasts the characteristic CSF profile in AD, i.e. depletion of amyloid beta peptide and increased phosphorylated and total tau.
Conclusions:
Combining SSVD and AD biomarkers may provide a powerful tool to identify with greater precision appropriate patients for clinical trials of more homogeneous dementia populations. Thereby, biomarkers might promote therapeutic progress not only in VCI-SSVD, but also in AD.
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