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

Wallin, A.; Kapaki, E.; Boban, M.; Engelborghs, S.; Hermann, D. M.; Huisa, B.; Jonsson, M.; Kramberger, M. G.; Lossi, L.; Malojcic, B.; Mehrabian, S.; Merighi, A.; Mukaetova-Ladinska, E. B.; Paraskevas, G. P.; Popescu, B. O.; Ravid, R.; Traykov, L.; Tsivgoulis, G.; Weinstein, G.; Korczyn, A.; Bjerke, M.; Rosenberg, G.

doi:10.1186/s12883-017-0877-3

Table 1 Summary of studies on candidate CSF biomarkers for VaD, VCI and SSVD according to their discrimination power (vs. Controls and/or AD)

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

Candidate biomarker	Study [Ref]	Date	Change	HC n	NC n	VaD n	VCI n	SSVD n	AD n	Difference vs. Controls	Difference vs. AD	Sn/Sp vs. Controls	Sn/Sp vs. AD
Albumin ratio (CSF/serum)	Wallin et al. [30]	1990	↑	30	-	53	-	-	-	P < 0.001	-	-	-
	Bjerke et al [72]	2009	→	52	-	-	-	9	20	NS	NS	-	-
	Bjerke et al. [33]	2011	↑	30	-	-	-	26	30	P < 0.005	P < 0.01	-	-
	Wallin et al. [32]	2001	↑	18	-	-	-	25	-	P < 0.001	-	-	-
NSE	Blennow et al. [41]	1994	↑	33	-	19	-	-	45	P < 0.0001	NS	-	-
TNF-α	Tarkowski et al. [55]	1999	↑	25	-	33	-	-	34	P < 0.001	-	-	-
VEGF	Tarkowski et al. [56]	2002	↑	27	-	26	-	-	20	P = 0.03	NS	-	-
TGF-beta	Tarkowski et al. [56]	2002	↑	27	-	26	-	-	20	P < 0.0004	NS	-	-
YKL-40	Olsson et al. [59]	2013	↑	-	65	19	-	-	-	P < 0.05	-	-	-
MMP-9	Adair et al. [62]	2004	↑	8	-	15	-	-	30	P < 0.003	P < 0.0001	-	-
MMP-9	Bjerke et al. [33]	2011	↑	30	-	-	-	26	30	P < 0.05	P < 0.05	-	-
MMP-10	Bjerke et al. [33]	2011	↑	30	-	-	-	26	30	P < 0.005	NS	-	-
MMP-2	Bjerke et al. [33]	2011	→	30	-	-	-	26	30	NS	NS	-	-
MMP-3	Bjerke et al. [33]	2011	→	30	-	-	-	26	30	NS	NS	-	-
TIMP-1	Ohrfelt et al. [57]	2011	↑	52	-	-	-	7	15	P = 0.01	-	-	-
	Ohrfelt et al. [57]	2011	↑	52	-	-	-	8	24	P = 0.03	-	-	-
	Bjerke et al. [33]	2011	↑	30	-	-	-	26	30	P < 0.05	P < 0.005	-	-
TIMP-2	Bjerke et al. [33]	2011	→	30	-	-	-	26	30	NS	NS	-	-
NF-L	Wallin et al. [32]	2001	↑	18	-	-	-	25	-	P < 0.001	-	Sn 68% Sp 85%	-
	Bjerke et al. [72]	2009	↑	52	-	-	-	9	20	P < 0.001	NS	-	-
	Bjerke et al. [33]	2011	↑	30	-	-	-	26	30	P < 0.0001	P < 0.05	-	-
MBP	Bjerke et al. [33]	2011	↑	30	-	-	-	26	30	P < 0.0001	P < 0.005	-	-
Sulfatide	Fredman et al. [85]	1992	↑	19	-	20	-	-	43	P < 0.0001	P < 0.0001	-	-
Total tau (τ_T)	Wallin et al. [32]	2001	→	18	-	-	-	25	-	NS	-	Sn 85% Sp 36%	-
	Paraskevas et al. [103]	2009	↑	68	_-	23	-_	-_	92	P < 0.05	P < 0.05	-_	Sn 80% Sp 86%
	Bjerke et al. [72]	2009	→	52	-	-	-	9	20	NS	P < 0.005	-	-
	Bjerke et al. [33]	2011	↑	30	-	-	-	26	30	P < 0.005	NS	-	-
Phospho-tau (τ_p-181)	Paraskevas et al. [103]	2009	→	68	-_	23	_-	-_	92	NS	P < 0.01	-_	Sn 84% Sp79%
	Bjerke et al. [72]	2009	→	52	-	-	-	9	20	NS	P < 0.005	-	-
	Bjerke et al. [33]	2011	→	30	-	-	-	26	30	NS	P < 0.05	-	-
Aβ₄₂	Paraskevas et al. [103]	2009	→	68	_-	23	-_	_-	92	NS	NS	-_	Sn 73% Sp 70%
	Bjerke et al. [72]	2009	↓	52	-	-	-	9	20	P < 0.05	P < 0.005	-	-
	Bjerke et al. [33]	2011	↓	30	-	-	-	26	30	P < 0.001	NS	-	-
Aβ₄₂, τ_T, τ_p-181 (combination)	Paraskevas et al. [103]	2009	↑	68	-_	23	-_	_-	92	NS	P < 0.01	_-	Sn 87% Sp 89%
sAPP_β	Bjerke et al. [77]	2014								Correlation with WML	-	-	-

VaD Vascular Dementia, VCI Vascular Cognitive Impairment, SSVD Subcortical Small Vessel Disease, AD Alzheimer’s disease, HC Healthy Controls, NC Neurological Controls, Sn/Sp Sensitivity/Specificity, n number of controls/patients, ↓ reduced levels, ↑ increased levels, → no difference vs. controls, − not included, NS Not Significant

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