Table 3 The systematic review of the level changes for inflammatory markers on PD non-motor symptoms.
From: A systematic review and meta-analysis of inflammatory biomarkers in Parkinson’s disease
No. | Author | Year | Sample source | Assay type | Sample size | Age | Markers | Scale | Summary |
|---|---|---|---|---|---|---|---|---|---|
Cognitive impairment | |||||||||
1 | Selikhova, M. V. | 2002 | Plasma | ELISA | 27 | 69.7 (8.9) | IL-6 | MMSE | No significant associations. |
2 | Dufek, M. | 2009 | serum | CLIA | 29 | 68.2 (5.4) | TNF-α | MMSE | No significant associations. |
3 | Menza, M. | 2010 | Plasma | ELISA | NA | NA | IL, TNF-α | MMSE | TNF-α was significantly correlated with cognition. |
4 | Scalzo, P. | 2010 | Serum | ELISA | 44 | NA | IL-6 | MMSE | Higher levels of IL-6 were associated with poor cognitive function. |
5 | Hassin-Baer, S. | 2011 | Plasma | CLIA | 73 | 68.8 (11.5) | CRP | MMSE | No significant associations. |
6 | Lee, H. W. | 2011 | Plasma | ELISA | 66 | 65.8 (8.8) | PTX3 | MMSE, CDR | No significant associations. |
7 | Lindqvist, D. | 2013 | CSF | MSD | 71 | 64.1 (10.5) | CRP, IL, TNF-α, chemokines | MMSE | MMSE score correlated significantly with IL-6 levels. |
8 | Rocha, N. P. | 2014 | Plasma | ELISA | 40 | 68.7 (10.1) | STNFR1, STNFR2 | MMSE, FAB | STNFR1 was a significant predictor for FAB score. |
9 | Rocha, N. P. | 2014 | Plasma | ELISA | 78 | 76.3 (5.0) | chemokines | MMSE | CXCL10 was associated with cognitive status. |
10 | Yu, S. Y. | 2014 | CSF | ELISA | 26 | 57.4 (10.8) | IL, TNF-α, INF-γ | MoCA | Negative correlation between MoCA score and IL-6. |
11 | Jiang, Q. W. | 2015 | Plasma | ELISA | 59 | 64.4 (8.1) | CCL3, CCL4 | MMSE | No significant associations. |
12 | Park, S. J. | 2015 | Serum | NA | 112 | 72.9 (5.7) | CRP | Diagnose | No significant associations. |
13 | Wennstrom, M. | 2015 | CSF | ELISA | 61 | 68.4 (9.2) | YKL-40 | MMSE | Negative correlation of CSF YKL-40 to MMSE. |
14 | Hall, S. | 2016 | CSF | ELISA | 63 | 64.7 (9.4) | YKL-40 | MMSE | An increase in YKL-40 correlated with worsening of cognitive function as measured by letter fluency. |
15 | Lue, L. F. | 2016 | Plasma | Multiplex | 74 | 73.1 (1.3) | Cytokines, chemokines | Diagnose | A 14-protein panel with age served as discriminants of PD dementia. |
CDR | Significant associations of TNF-α, IL-2, CCL7, IL-17, CCL26, CCL13, IL-16 and BDNF. | ||||||||
MMSE | Significant associations of IL-1β. | ||||||||
AVLT-A7 | Significant associations of CCL2, IL-17R, CCL11. | ||||||||
16 | Williams-Gray, C. H. | 2016 | Serum | V-PLEX | 230 | 66.4 (9.5) | IFN-γ, IL, TNF-α, CRP | MMSE | IFN-γ, TNF-α, IL-6, and CRP levels were associated with lower MMSE scores, while IL-1β and IL-2 were correlated with faster rate of cognitive decline. |
17 | Hall, S. | 2018 | CSF | MSD | 131 | 64.9 (10.6) | CRP, SAA, YKL-40, CCL2 | Diagnose | CRP and SAA were higher in patients with PD dementia. The levels of CCL2 in CSF were lower in PD dementia. |
18 | Karpenko, M. N. | 2018 | Serum | ELISA | 117 | 65 (57-73) | IL, TNF-α | MMSE | The serum level of TNF-α was significantly lower in PD patients with MCI. |
19 | Kim, R. | 2018 | Serum | MSD | 58 | 62.4 (8.1) | IL, TNF-α, CRP | MoCA | No significant associations. |
20 | Moghaddam, H. S. | 2018 | CSF | NA | 109 | 69.7 (6.5) | CRP | MoCA | A significant correlation was observed. |
21 | Rocha, N. P. | 2018 | Plasma | CBA | 40 | 68.7 (10.1) | IL, TNF, IFN-γ | MMSE | Higher TNF/IL-10 ratios were associated with worse cognitive performance. |
22 | Veselý, B. | 2018 | Serum | CLIA | 47 | 65 (7.8) | IL-6 | MMSE | No significant associations. |
23 | Green, H. F. | 2019 | Plasma | SIMOA | 63 | 69.9 (8.1) | IL, TNF-α, TGF-β | MoCA | IL-17A was negatively correlated with MoCA score. |
24 | King, E. | 2019 | Serum | MSD | 112 | 69.5 (6.7) | TNF‐α, IL, IFN‐γ, CRP | MoCA | IL‐8 was significantly higher in PD without MCI. |
25 | Chatterjee, K. | 2020 | Serum | ELISA | 27 | 62.5 (7.7) | IL-1β, NLRP3 | MMSE, DRS-2 | No significant associations. |
26 | Kiçik, A. | 2020 | Serum | ELISA | 61 | NA | NLRP3, IL-1β, IL-18 | Diagnose | PD-MCI patients displayed significantly reduced serum IL-1β and IL-18 levels. |
27 | Martin-Ruiz, C. | 2020 | Serum | MSD | 154 | 67 (60-82) | CRP, IL-6 | MMSE, MoCA | Levels of CRP and IL-6 were significantly raised in PD-MCI cases. |
28 | Santaella, A. | 2020 | CSF | ELISA | 46 | 57.5 (10.0) | CCL2 | MMSE | No significant associations. |
29 | Bartl, M. | 2021 | CSF | ELISA | 252 | 61 (9.8) | GFAP, S100β, YKL-40, sTREM2 | MoCA | The MoCA score showed a significant negative correlation with GFAP, S100, YKL-40 and sTREM2. |
30 | Galper, J. | 2021 | Plasma | Bio-Plex | 75 | 62.4 (1.2) | TNF-α, IL, chemokines, PDGF | MoCA | MoCA score significantly negatively correlated to IL-17RA, CXCL10, CCL3, and CCL18, and positively correlated to PDGF. |
31 | Lerche, S. | 2022 | CSF | Multiplex | 68 | - | ICAM-1, IL, CCL2, TNF-α | MoCA | Higher CSF levels of IL-8 and CCL2 were associated with lower MoCA scores. |
32 | Li, Y. Y. | 2022 | Plasma | MSD | 76 | 62.2 (7.5) | Chemokines, IL-8 | MMSE | An increase in CCL15 levels was associated with an increased MMSE score. |
Depression and anxiety | |||||||||
1 | Selikhova, M. V. | 2002 | Plasma | ELISA | 27 | 69.7 (8.9) | IL-6 | BDI | Significant positive association. |
STAI | No significant associations. | ||||||||
2 | Menza, M. | 2010 | Plasma | ELISA | NA | NA | IL, TNF-α | HAMD | TNF-α was significantly correlated with depression. |
3 | Pålhagen, S. | 2010 | CSF | EIAs | 25 | 64.9 (8.4) | IL-6 | HAMD MADRS | No significant associations. |
4 | Lindqvist, D. | 2012 | Serum | MSD | 86 | 64.2 (10.8) | CRP, IL-6, IL-2R, TNF-α | HADS | TNF-α and sIL-2R were positively correlated with HAD depression scores. |
TNF-α and sIL-2R were positively correlated with HAD anxiety scores. | |||||||||
5 | Lindqvist, D. | 2013 | CSF | MSD | 71 | 64.1 (10.5) | CRP, IL-6, TNF-α, chemokines | HADS | HADS depression score correlated positively with CRP and MCP-1 and IP-10. |
6 | Rocha, N. P. | 2014 | Plasma | ELISA | 78 | 76.3 (5.0) | chemokines | BDI | No significant associations. |
7 | Jiang, Q. W. | 2015 | Plasma | ELISA | 59 | 64.4 (8.1) | CCL3, CCL4 | HAMD | MIP-1α was correlated with depression in early PD. |
8 | Li, Z. J. | 2016 | Serum | ELISA | 65 | 64.6 (8.2) | IL-6, IL-18, TNF-α, CRP | HAMD | Serum IL-6, IL-1β, TNF-α and CRP were significantly higher. |
9 | Wang, X. M. | 2016 | Blood | ELISA | 62 | 65.0 (7.2) | IL-1β, IL-6, INF-γ, CRP, sIL-2R | HAMD | HAMD scores were positively correlated with the levels of TNF-α, CRP and sIL-2R of PD patients. |
HAMA | HAMA scores were positively correlated with the levels of TNF-α, CRP and sIL-2R of PD patients. | ||||||||
10 | Hall, S. | 2018 | CSF | MSD | 131 | 64.9 (10.6) | CRP, SAA, YKL-40, CCL2 | HADS | Increased depressive symptoms correlated with CRP and SAA. |
11 | Karpenko, M. N. | 2018 | Serum | ELISA | 117 | 65 (57-73) | IL, TNF-α | HADS | A direct correlation was only found between the level of serum IL-10 and depression. |
HADS | A correlation was found between the level of serum IL-10 and anxiety. | ||||||||
12 | Veselý, B. | 2018 | Serum | CLIA | 47 | 65 (7.8) | IL-6 | MADRS | Patients with higher IL-6 at baseline showed worse depression scores at 2 years. |
13 | Ahmadi Rastegar, D. | 2019 | Serum | Multiplex | 65 | NA | IL, G-CSF, chemokines, TNF-α, FGF basic, VEGF | GDS | Fourteen cytokines positively correlated with the fold change in geriatric depression scale over the 2-year time period. |
14 | Green, H. F. | 2019 | Plasma | SIMOA | 63 | 69.9 (8.1) | IL, TNF-α, TGF-β | HADS | No significant associations. |
HADS | IL-17A was positively correlated with the anxiety subscale of HADS. | ||||||||
15 | Lian, T. H. | 2020 | CSF | ELISA | 86 | 62.2 (9.5) | TNF-α | HAMD | TNF-α played an important role in PD depression. |
16 | Zhu, Y. | 2021 | Serum | ELISA | 46 | 69.5 (9.6) | IL-6, TNF-α, sLAG3 | HAMD | No significant associations. |
HAMA | Serum TNF-α and sLAG3 positively correlated with HAMA. | ||||||||
Sleep disorders | |||||||||
1 | Menza, M. | 2010 | Plasma | ELISA | NA | NA | IL, TNF-α | PSQI | No significant associations. |
2 | Hassin-Baer, S. | 2011 | Plasma | Chemical | 73 | 68.8 (11.5) | CRP | Self-reported | No significant associations. |
3 | Lindqvist, D. | 2012 | Serum | MSD | 86 | 64.2 (10.8) | CRP, IL, TNF-α | SCOPA-S | No significant associations. |
4 | Hu, Y. | 2015 | CSF | ELISA | 84 | NA | NO, H2O2, IL-1β, TNF-α | RBDSQ | Enhanced RBDSQ scores with elevated levels of NO and IL-1β in the CSF of patients with PD. |
5 | Jiang, Q. W. | 2015 | Plasma | ELISA | 59 | 64.4 (8.1) | CCL3, CCL4 | RBDSQ | CCL3 was correlated with RBD in early PD. |
6 | Hu, Y. | 2021 | CSF/Serum | ELISA | 139 | NA | IL-1β, TNF-α | EDS | ESS scored higher as IL-1β concentration in CSF elevated in patients with PD. |
7 | Mo, M. S. | 2021 | CSF | ELISA | 80 | 63.6 (8.5) | sTREM2 | PDSS | PD patients with a moderate or severe sleep disorder had a significantly increased concentration of sTREM2 in their CSF. |
8 | Kaminska, M. | 2022 | Serum | Multiplex | 66 | 64.6 (9.8) | IL, TNF-α, BDNF | Polysomnography | IL-6 was associated with some polysomnographic characteristics. |
ESS | No significant associations. | ||||||||
9 | Wang, L. X. | 2022 | Blood | NA | 93 | 61 (51-68) | CRP | NA | CRP levels served as biomarkers and predicted the prognosis of PD patients with RBD. |
10 | Yuan, Y. | 2022 | CSF/Serum | EIA | 13 | NA | TNF-α | RBDQ | No significant associations. |
Fatigue | |||||||||
1 | Lindqvist, D. | 2012 | Serum | MSD | 86 | 64.2 (10.8) | CRP, IL-6, TNF-α, chemokines | FACIT | TNF-α and sIL-2R were positively correlated with FACIT scores. |
2 | Lindqvist, D. | 2013 | CSF | MSD | 71 | 64.1 (10.5) | CRP, IL-6, TNF-α, chemokines | FACIT | FACIT score correlated negatively with CRP, CXCL10, and CCL2. |
3 | Pereira, J. R. | 2016 | Serum | ELISA | 44 | 65.1 (10.9) | IL-6, STNFR1, STNFR2 | PFS | Fatigued PD patients have elevated IL-6 serum levels when compared with non-fatigued patients. |
4 | Hall, S. | 2018 | CSF | MSD | 131 | 64.9 (10.6) | CRP, SAA, YKL-40, CCL2 | FACIT | Increased fatigue symptoms correlated with CRP and SAA. |
Neuropsychiatric symptoms | |||||||||
1 | Hassin-Baer, S. | 2011 | Plasma | Chemical | 73 | 68.8 (11.5) | CRP | PPRS, AS, BDI | No significant associations. |
2 | Sawada, H. | 2014 | Plasma | - | 111 | 69.7 (7.8) | CRP | PPQ-A | Subclinical elevations of CRP levels might be an independent risk for hallucinations/illusions. |
3 | Wang, Y. H. | 2015 | Plasma | Nephelometric | 62 | 65.8 (9.3) | CRP, IL-6 | PPQ-B | The levels of IL-6 and CRP were significantly higher in hallucination group. |
Autonomic function | |||||||||
1 | Jiang, Q. W. | 2015 | Plasma | ELISA | 59 | 64.4 (8.1) | CCL3, CCL4 | SCOPA-AUT | No significant associations. |
