Biochemical markers in vascular cognitive impairment associated with subcortical small vessel disease - A consensus report

被引：73

作者：

Wallin, A. ^{[1
,19
]}

Kapaki, E. ^{[2
]}

Boban, M. ^{[3
]}

Engelborghs, S. ^{[4
,5
,6
]}

Hermann, D. M. ^{[7
]}

Huisa, B. ^{[8
]}

Jonsson, M. ^{[1
]}

Kramberger, M. G. ^{[9
]}

Lossi, L. ^{[10
]}

Malojcic, B. ^{[3
]}

Mehrabian, S. ^{[11
]}

Merighi, A. ^{[10
]}

Mukaetova-Ladinska, E. B. ^{[12
]}

Paraskevas, G. P. ^{[2
]}

Popescu, B. O. ^{[13
]}

Ravid, R. ^{[14
]}

Traykov, L. ^{[11
]}

Tsivgoulis, G. ^{[15
]}

Weinstein, G. ^{[16
]}

Korczyn, A. ^{[17
]}

Bjerke, M.

Rosenberg, G. ^{[18
]}

机构：

[1] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden

[2] Univ Athens, Med Sch, Eginit Hosp, Dept Neurol 1, Athens, Greece

[3] Univ Zagreb, Med Sch, Univ Hosp Ctr Zagreb, Dept Neurol, Zagreb, Croatia

[4] Hosp Network Antwerp ZNA Middelheim & HogeBeuken, Memory Clin, Antwerp, Belgium

[5] Hosp Network Antwerp ZNA Middelheim & HogeBeuken, Dept Neurol, Antwerp, Belgium

[6] Univ Antwerp, Inst Born Bunge, Reference Ctr Biol Markers Dementia, Dept Biomed Sci, Antwerp, Belgium

[7] Univ Hosp Essen, Dept Neurol, Essen, Germany

[8] Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA

[9] Univ Med Ctr Ljubljana, Dept Neurol, Ljubljana, Slovenia

[10] Univ Turin, Dept Vet Sci, Turin, Italy

[11] Med Univ, Univ Hosp Alexandrovska, Dept Neurol, Sofia, Bulgaria

[12] Newcastle Univ, Inst Neurosci, Campus Ageing & Vital, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England

[13] Carol Davila Univ Med & Pharm, Sch Med, Colentina Clin Hosp, Dept Neurol, Bucharest, Romania

[14] Brain Bank Consultants, Amsterdam, Netherlands

[15] Univ Athens, Sch Med, Dept Neurol 2, Attikon Hosp, Athens, Greece

[16] Univ Haifa, Sch Publ Hlth, Haifa, Israel

[17] Tel Aviv Univ, Sackler Sch Med, Dept Neurol, Tel Aviv, Israel

[18] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA

[19] Univ Gothenburg, Dept Neuropsychiat, Sahlgrenska Univ Hosp, Sahlgrenska Acad,Inst Neurosci & Physiol,Memory C, Wallinsgatan 6, SE-43141 Molndal, Sweden

来源：

BMC NEUROLOGY | 2017年 / 17卷

关键词：

Vascular cognitive impairment; Subcortical small vessel disease; Biomarkers; Blood; CSF; Alzheimer's disease; Mixed type dementia; Dementia; WHITE-MATTER LESIONS; CEREBROSPINAL-FLUID TAU; BRAIN-BARRIER FUNCTION; CENTRAL-NERVOUS-SYSTEM; ACUTE ISCHEMIC-STROKE; VON-WILLEBRAND-FACTOR; C-REACTIVE PROTEIN; ALZHEIMERS-DISEASE; MATRIX METALLOPROTEINASES; NEUROFILAMENT PROTEIN;

D O I：

10.1186/s12883-017-0877-3

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页数：12

共 157 条

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