Table 1.
Characteristics of cross-sectional studies investigating relationship between inflammatory markers and vascular dementia
| Study (country) | Population | Sample size | Mean age | Inflammatory biomarkers | Covariates | Diagnostic criteria | Main results |
|---|---|---|---|---|---|---|---|
| Zhang, 2017 (China) | Subjects with VCI with no dementia, VaD and cognitively healthy (CON) |
VaD: 30 Mild VCI: 30 CON: 30 |
65.7 y | CRP, IL-6, TNF-α [serum] | - |
VaD: MoCA, CDR, ADL and HIS MRI scan |
Higher CRP, IL-6 and TNF-α in VaD vs mild VCI or CON (p < 0.05) |
| Dukic, 2016 (Croatia) | Patients older than 60 years with AD, VaD, MCI or cognitively healthy (CON) |
VaD: 67 MCI: 48 AD: 70 CON: 50 |
73.0 y | CRP, IL-6 [serum] | - |
VaD: NINDS-AIREN criteria AD: NIA-AA 2011 criteria MCI: Petersen's criteria CT scan |
Higher IL-6 in VaD vs AD, MCI or CON (p = 0.014) Lower CRP in AD |
| Uslu, 2012 (Turkey) | Newly diagnosed, randomly chosen AD, VaD patients and or cognitively healthy (CON) |
VaD: 16 AD: 28 CON: 23 |
68.4 y | IL-6, TNF-α [serum] | - |
AD: NINCDS-ADRDA criteria VaD: NINDS- AIREN criteria |
IL-6 and TNF-α levels did not differ significantly across AD, VaD and CON |
| Li, 2010 (Germany) | Community dwelling subjects with AD, VaD, cognitive impairment, or cognitively healthy (CON) |
VaD: 16 MCI: 17 AD: 28 CON: 22 |
78.5 y | hs-CRP [serum] | - |
AD: NINCDS-ADRDA criteria VaD: NINDS- AIREN criteria MCI: Petersen's criteria |
Trend toward higher hs-CRP in all disease groups (AD, VaD, MCI) vs CON |
| Jia, 2005 (China) | Hospitalized patients with AD, VaD, or cognitively healthy cases with peripheral nerve diseases (CON) |
VaD: 38 AD: 39 CON: 35 |
64.2 y | IL-1α, IL-1β, IL-2, IL-6, TNF-α, T-tau, P-tau, Aβ1–42 [CSF] | - |
AD: NINCDS-ADRDA criteria VaD: NINDS- AIREN criteria |
Higher CSF IL-6 in AD and VaD vs CON (p < 0.01), no significant difference between AD and VaD Higher CSF TNF-α in AD vs CON (p < 0.01), and lower vs VaD (p < 0.01) |
| Wada-Isoe, 2004 (Japan) | Patients with AD, VaD, CVND, and other neurological disorders without cognitive impairment (CON) |
VaD: 11 AD: 26 CVND: 11 CON: 21 |
69.0 y | IL-6 [CSF] | - |
AD: DSM-III-R, NINCDS-ADRDA criteria and HIS ≤ 4 VaD: DSM-III-R, ADDTC criteria and HIS ≥ 7 CT scan or MRI and SPECT |
Higher CSF IL-6 in VaD vs AD (p < 0.01) or CON (p < 0.01) |
| Paganelli, 2002 (Italy) | Community dwelling subjects with AD, VaD or mixed dementia |
VaD: 18 AD: 36 (25 mild AD, 11 severe AD) MIX: 16 |
76.7 y | IL-1β, TNFα [serum] | - |
AD: NINCDS-ADRDA criteria VaD: NINDS- AIREN criteria CT or MRI scan |
Lower TNF-α in mild-moderate AD vs severe AD (p < 0.001), VaD (p < 0.001) and MIX (p < 0.001) Lower TNF-α/IL-1β ratio in mild-moderate AD vs VaD and MIX |
| De Luigi, 2001 (Switzerland) | Patients with different types of dementia, cognitive impairment, or cognitively healthy (CON) |
VaD: 7 AD: 44 MIX: 10 Uncertain dementia: 18 MCI: 12 CON: 42 |
Not reported | TNF-α, IL-1β, sTNF-RI, IL-1Ra, IL-10 [plasma] | - |
VaD: modified HIS > 4 AD: NINCDS-ADRDA criteria |
Higher TNF-α, sTNF-RI in VaD vs CON (p < 0.001) After LPS stimulus reduced production of TNF-α in all dementia groups and of IL-10 in VaD |
| Zuliani, 2007 (Italy) | Patients with AD, VaD, CDND, and cognitively healthy (CON) |
VaD: 80 AD: 60 CVND: 40 CON: 42 |
76.4 y | IL-6, TNF-α, IL-1β, IL-10 [serum] | Age, gender, coronary heart disease, diabetes, hypertension, smoking, and alcohol consumption |
AD: NINCDS-ADRDA criteria VaD: NINDS- AIREN criteria CT scan |
Higher IL-1β in VaD, AD, and CDND vs CON (p < 0.005) Higher TNF-α in VaD and AD vs CON (p < 0.05), and in VaD vs AD (p < 0.03) Higher IL-6 in VaD vs AD (p < 0.03) |
| Tarkowski, 1999 (Sweden) | Patients with AD, VaD or cognitively healthy (CON) |
AD: 34 VaD: 33 CON: 55 (25 with CSF assessment) |
66.7 y | TNF-α, IL-1β, IL-6 [serum and CSF] | - |
AD: according definition of “pure” AD by Wallin et al. (1994) VaD: NINDS- AIREN criteria CT scan |
Higher TNF-α in the CSF of AD (p = 0.006) and VaD patients (p = 0.001) vs CON No difference in TNF-α serum level between AD, VaD and CON Higher TNF-α in CSF than in the sera in patients with AD (p = 0.039) and with VaD (p = 0.007) Higher serum IL-6 in VaD vs CON (p < 0.0001) and vs CSF IL-6 (p = 0.002) No difference in CSF and serum IL-6 and IL-1β levels between AD and VaD |
| Wehr, 2019 (Poland) | Patients with different types of dementia, or cognitively healthy (CON) |
AD: 166 VaD: 85 MIX: 149 CON: 180 |
73.3 y | IL-6, hs-CRP, chitotriosidase activity, paraoxonase-1 [serum] | - |
AD: NINCDS-ADRDA criteria VaD: NINDS- AIREN criteria CT or MRI scan |
Higher IL-6 in the whole dementia group and in the VaD, MIX groups vs CON Higher hs-CRP in the VaD group Higher chitotriosidase activity in VaD and MIX but not in AD |
| Vishnu, 2017 (India) | Patients with different types of dementia or cognitive impairment |
AD: 41 VaD: 11 MCI: 11 Mild VCI: 5 |
- | Fibrinogen, D-dimer, IL-6, CRP [plasma] | - |
AD: Dubois criteria, VaD: DSM IV criteria MCI/mild VCI: NIA-AA criteria MRI, FDG-PET and CSF biomarkers |
No difference in IL-6 and CRP between AD and VaD Higher fibrinogen in VaD Higher D-dimer levels in VaD |
| Mancinella, 2009 (Italy) | Patients with different types of dementia, or cognitively healthy (CON) |
AD: 35 VaD: 64 CON: 99 |
83.5 y | Fibrinogen, hs-CRP [plasma] | - |
AD: NINCDS-ADRDA criteria VaD: NINDS- AIREN criteria CT or MRI scan |
Higher hs-CRP in dementia group vs control and in AD vs VaD |
Abbreviations: AD Alzheimer’s disease, ADDTC Alzheimer’s Disease Diagnostic and Treatment Centers, ADL activities of daily living scale, CDR clinical dementia rating, CON controls, CRP c-reactive protein, CSF cerebrospinal fluid, CT computed tomography, CVND cerebrovascular disease but without dementia, FDG-PET 18fluoro-2-deoxyglucose positron emission tomography, IL interleukin, HIS Hachinski Ischemic Scale, hs-CRP high sensitive c-reactive protein, MCI mild cognitive impairment, MIX mixed dementia, MoCA montreal cognitive assessment, MRI magnetic resonance imaging, NIA-AA National Institute on Aging-Alzheimer’s Association, NINCDS-ADRDA National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and related Disorders Association, NINDS-AIREN National Institute of Neurological Disorders and Stroke–Association Internationale pour la Recherche et l’Enseignement en Neurosciences, SCI subjective cognitive impairment, SPECT single photon emission computed tomography, sTNF-RI soluble tumor necrosis factor receptor type I, TNF tumor necrosis factor, VaD vascular dementia, VCI vascular cognitive impairment