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Supplementary Table 1. Example of literature search strategy using EMBASE database. # Searches Results [Question: Do patients with Alzheimer’s Disease have peripheral inflammatory 1 0 factors or cerebrospinal fluids that are different from healthy controls?] 2 [Concept 1: Alzheimer Disease] 0 3 Alzheimer Disease/ 138188 4 Alzheimer*.tw,kw. 138322 5 3 or 4 166124 6 [Concept 2: Inflammatory Factors] 0 7 exp cytokine/ 1105934 8 exp acute phase protein/ 7978 9 Kynurenine 4260 10 Kyurenic Acid/ 3089 11 exp quinolinic acid derivative/ 115 12 indoleamine 2,3 dioxygenase 3696 13 exp cell adhesion molecule/ 28825 14 exp immunoglobulin 413921 15 exp adipocytokine 9480 16 exp vasculotropin 74251 17 (interleukin* or IL*).tw,kw. 1350378 18 (acute-phase protein* or acute phase protein*).tw.kw. 7174 ((Tumour Necrosis Factor* or tnf* or tumour necrosis factor*) adj2 19 152399 alpha).tw,kw. 20 ((interferon or IFN) adj2 gamma).tw,kw. 33062 (CCL or MCP 1 or monocyte chemoattractant protein 1 or monocyte 21 27633 chemotactic protein 1).tw,kw.

(chemokine* adj2 (ccl2 or ccl 2 or ccl3* or ccl 3 or ccl10 or ccl 10 or ccl11 or 22 3084 ccl 11 or ip 10 or cxcl10 or cxcl 10)).tw,kw. 23 (monocyte chemoattractant protein or monocyte chemotactic protein).tw,kw. 12960 24 (macrophage inflammatory protein adj2 1 alpha).tw,kw. 316 25 (Macrophage Colony-Stimulating Factor or MCSF or m-csf or csf-m).tw,kw. 20113 26 ((Transforming Growth Factor or tgf) adj2 beta.tw,kw. 56538 27 (Vascular Endothelial Growth Factor or VEGF).tw,kw. 81022 28 (CRP or c reactive protein or c-reactive protein or protein c-reactive).tw,kw. 88037 29 (adipokine* or adipocytokine*).tw,kw. 13638 30 Fibrinogen*.tw,kw. 57034 31 (acid* adj2 (kynurenic or quinolinic)).tw,kw. 4385 32 kynureni*.tw,kw. 5974 33 (cell adhesion molecule* or ICAM or VCAM).tw,kw. 46648 34 (cytokine* or quinolinic or immunoglobulin*).tw,kw. 515430 35 or/7-34 2748049 36 [Concept 3: Limit Ifs to peripheral & CSF] 0 37 exp Biological Marker/ and peripher*.tw,kw. 7701 38 Cerebrospinal Fluid/ 106021 39 exp Plasma/ 163145 40 exp Serum/ 257277 41 (peripher* and (biomarker* or marker*)).tw,kw. 49477 42 (plasma* or serum or sera).tw,kw. 2092590 43 ((cerebro spinal or cerebrospinal) adj2 fluid*).tw,kw. 87976 44 or/37-43 2276221 45 5 and 35 and 44 2560 46 [Limit to Specific Study Types] 0 47 exp “types of study”/ 2.3E+07 48 exp “sensitivity and specificity”/ 232591 49 exp diagnostic error/ 67770 50 statistical model 119498 51 exp prognosis/ 533028 52 exp morbidity/ 267272 53 exp mortality/ 783633 54 exp survival/ 737466 55 prognos*.tw. 614388 56 predict*.tw. 1352019 57 course*.tw. 720715 58 diagnosed.tw. 596300 59 cohort*.tw. 497611 60 death.tw. 710298 61 (evaluation adj1 (study or studies)).mp. 25295 62 (validation adj1 (study or studies)).mp. 59613 63 (likelihood: or likelihood ratio:).mp. 123175 64 exp immunoassay/ 427273 ((enzyme-linked immunosorbent or enzyme linked immunosorbent or 65 74169 multiplex) adj3 (assay or analysis)).tw,kw. (((plasma or TNF* or tumor necrosis factor*) adj2 (level* or concentration*)) 66 121740 and compare*).tw. 67 or/47-66 2.4E+07 68 45 and 67 2498 69 [Limit to Human] 0 70 exp animal/ not (exp human/ and exp animal/) 4782503 71 68 not 70 2160

Supplementary Table 2. Characteristics of included studies.

Alzheimer's Disease Study Study Characteristics Methodology Healthy Control Demographics Demographics

Exclud Exclud Exclu ed ed Gen ded Age Patient Anti- Alzheimer' % der Psych % BMI BMI Mat s with inflam s Disease Plasma/ Age MMS Age m MM Mat iatric Assay Type N mal (kg/ N (kg/ ched Inflam matory Diagnostic Serum (yrs) E (yrs) al SE ched Illnes e m2) m2) (y/n) matory Medica Criteria e (y/n) ses Diseas tions (y/n) e (y/n) (y/n) Al- 17.37 26.66 khateeb, 5 70.7 ± 37 ± 68.9 ± 66 ± 2014 n n y n n DSM-IV Spectroscopy serum 2 7.62 % 3.49 N/A 50 7.11 % 2.78 N/A Al- 14.9 25.19 khateeb, NINCDS- Colorimetric 4 71.5 ± 63 ± 68.46 61 ± 2015 n n y n n ADRDA Method serum 0 9.11 % 5.57 N/A 41 ± 8.13 % 2.61 N/A Alsadany NINCDS- , 2012 ADRDA, 2 72.2 ± 44 12.56 72.8 ± 48 27.8 y y y n y DSM-IV ELISA plasma 5 5.9 % ± 5.8 N/A 25 4.1 % ± 4.4 N/A Altstiel, NINCDS- 7 74.9 N/ 71.0 ± N/ 1995 y n n y n ADRDA ELISA serum 7 ±9.8 A N/A N/A 48 8.6 A N/A N/A Alvarez, NINCDS- serum 25.95 33.89 1996 ADRDA, and 2 66.6 ± 50 ± 65.6 ± 45 ± y n n n n DSM-IV RIA, ELISA plasma 0 6.4 % 5.39* N/A 20 5.8 % 1.28* N/A Alvarez, NINCDS- 1 2007 ADRDA, 4 75.25 30 68.86 33 n n y n n DSM-IV ELISA serum 1 ± 8.59 % N/A N/A 30 ± 8.77 % N/A N/A Angelop oulos, NINCDS- 5 72 ± N/ 59.2 ± N/ 2008 n n n y n ADRDA ELISA serum 6 8.6 A N/A N/A 16 9.1 A N/A N/A Araga, DSM-III- 5 78.5 ± 14 7.5 ± 77.0 ± 19 29.4 1991 n n n n n R ELISA serum 0 6.4 % 7.1 N/A 37 7.3 % ± 1.0 N/A Bai, NINCDS- ELISA, 7 81 ± 53 4.0 ± 78 ± 63 27 ± 2013 y y n y n ADRDA Spectroscopy plasma 6 37 % 13.0 N/A 40 33 % 2.0 N/A Balldin, 1 2012 NINCDS- Multiplex 2 76.72 38 22.3± 19 70.47 65 29.4 n n n n n ADRDA ELISA serum 4 ± 7.80 % 4.1 N/A 6 ± 8.81 % ± 0.9 N/A Baraczka 3 61.8 ± N/ 62 ± N/ , 1995 y n n n n N/A N/A Serum 2 9.4 A N/A N/A 10 5.9 A N/A N/A Baranow Neuropsyc ska-Bik, hological 2008 Assessmen t and 5 73.19 16.05 72.85 0 n y n n n Imaging ELISA plasma 7 ± 4.09 0% ± 6.3 N/A 67 ± 5.64 % N/A N/A Baranow 24.5 25.9 ska-Bik, NINCDS- 5 73.9 ± 17.9 ± 72.7 ± 0 ± 2015 y n n n n ADRDA RIA plasma 8 4.6 0% ± 5.7 3.6 42 6.3 % >27 4.0 Belkhelf 2 76.8 ± 56 18 ± 44 29 ± a, 2014 n n n y n N/A ELISA plasma 5 6.53 % 6 N/A 9 73 ± 7 % 2 N/A Bermejo, NINCDS- 4 79.7 ± N/ 80.4 ± N/ 2008 y n y n n ADRDA ELISA plasma 5 0.9 A N/A N/A 28 2.0 A N/A N/A Biella, NINCDS- Multiplex 3 76.8 ± 30 74.7 ± 48 2013 n n n n n ADRDA ELISA serum 3 7.5 % N/A N/A 23 8.6 % N/A N/A NINCDS- Bigalke, ADRDA, 4 74.3 ± 46 19.9 ≥30 67.3 ± 51 29.4 2011 y n y n n DSM-IV ELISA plasma 1 9.1 % ± 4.6 6 37 10.2 % ± 0.6 ≥30 Quantibody Human Cytokine NINCDS- Antibody ADRDA, Array, 1 Bjorkqvi DSM-III- Electrochemol 4 73.7 ± 71 21 ± 17 77.25 77 29 ± st, 2012 n n n n n R uminescence plasma 2 5.9 % 0.4 N/A 4 ± 6.8 % 0.1 N/A Blum- Degen, NINCDS- 1 65 ± 82 61 ± 50 1995 n n n n n ADRDA ELISA plasma 1 3.58 % N/A N/A 12 4.15 % N/A N/A ELISA, 1 23.2 23.5 Bozluolc NINCDS- Immunonephel 4 73.0 ± 46 16.29 ± 73.1 ± 52 27.5 ± ay, 2016 y y y y n ADRDA ometry serum 5 9.9 % ± 3.9 3.1 25 10.6 % ± 1.7 3.2 serum Bonaccor and 1 78.4 ± 20 75.6 ± 53 so, 1998 n n y n n DSM-II-R ELISA, HPLC plasma 5 10.3 % N/A N/A 15 9.1 % N/A N/A Bonotis, NINCDS- 4 75.84 21 15.8 71.23 48 28.33 2008 y n y y y ADRDA ELISA serum 9 ± 6.17 % ± 5.8 N/A 21 ± 4.4 % ± 1.3 N/A Borroni, NINCDS- 2002 ADRDA, serum DSM-IV- ELISA, Clauss and 3 68.2 ± 43 22.1 71.0 ± 40 27.9 y y y n n R Method plasma 0 10.3 % ± 5.6 N/A 30 8.8 % ± 1.3 N/A Cacabelo NINCDS- s, 1991 ADRDA, 70.05 18.8 32.62 DSM-III- 1 ± N/ ± 57.8 ± N/ ± n n y n n R RIA serum 6 11.04 A 8.7* N/A 8 7.3 A 2.50* N/A NINCDS- ADRDA, Cacabelo DSM-III- 1 66.16 N/ 66.37 N/ s, 1993 n n n n n R RIA serum 8 ± 8.89 A N/A N/A 8 ± 4.42 A N/A N/A Cacabelo NINCDS- s, 1994 ADRDA, 19.35 33.2 DSM-III- 1 67.5 ± 43 ± 65.9 ± 50 ± n n y n n R ELISA serum 4 8.2 % 7.4* N/A 12 8.5 % 1.82* N/A Cestari, NINCDS- Multiplex 2 77.68 40 75.33 33 2016 y y y n n ADRDA Assay serum 5 ± 6.03 % N/A N/A 21 ± 5.75 % N/A N/A Chakraba 10.27 22.0 29.10 23.4 rti, 2014 6 66.97 55 ± 2 ± 64.75 57 ± 8 ± y y y n n DSM-IV ELISA serum 0 ± 6.36 % 3.77 2.20 60 ± 4.40 % 0.72 1.59 Chao, NINCDS- Murine 2 71.35 50 70.1 ± 50 1994a n n n n n ADRDA Bioassay serum 2 ± 2.23 % N/A N/A 22 2.1 % N/A N/A Chao, Autopsy 33 33 1994b y y n n n confirmed Bioassay serum 6 83 ± 3 % N/A N/A 6 71 ± 5 % N/A N/A Chen, 22.6 24.6 2012 NINCDS- 4 70.19 49 19.7 ± 66.9± 50 30± ± n n n y y ADRDA ELISA serum 3 ± 11 % ± 6.2 3.1 22 6.7 % 0 3.2 Chen, National 2014 Institute on Aging- Alzheimer' s Associatio 5 76.6 ± 30 11.4 76.6 ± 30 23.1 y y n n n n Criteria ELISA serum 3 6.7 % ± 4.0 N/A 53 6.7 % ± 3.7 N/A Chiappel NINCDS- 3 li, 2006 ADRDA, 1 76.24 32 32 55 n n n n n DSM-II-R Biochip Array plasma 7 ± 7.77 % N/A N/A 0 73 ± 5 % N/A N/A Choi, NINCDS- Multiplex 1 73.5 ± 18 68.5 ± 38 2008 n n y y y ADRDA Assay serum 1 4.0 % N/A N/A 13 7.2 % N/A N/A 24.9 25.5 Ciabatto NINCDS_ ELISA, 4 43 17 ± ± 39 29 ± ± ni, 2007 y y y y n ADRDA Immunoassay plasma 4 73 ± 8 % 4 1.6 44 75 ± 7 % 1 1.7 Cojocaru Neuropsyc , 2011 hological 70.43 70.17 Assessmen 4 ± 43 ± 47 n n n n n t ELISA serum 7 10.82 % N/A N/A 47 10.64 % N/A N/A Corsi, NINCDS- 2011 ADRDA, DSM-III- 7 75.6 ± 39 73.4 ± 33 n n n n n R Biochip Array plasma 2 7.2 % N/A N/A 6 1.1 % N/A N/A Davis, DSM-IV- 2007 TR, Immunoassay, serum 16.67 27.52 NINCDS- Immunoturbid and 1 N/ ± 69.5 ± N/ ± n n n n n ADRDA metric Assay plasma 9 N/A A 1.47 N/A 46 0.95 A 0.45 N/A Davis, Immunoassay, 2009 DSM-IV- Immunoturbid TR, metric Assay, serum 27.52 NINCDS- Spectrophotom and 1 N/ 16.67 N/ ± y n n n n ADRDA etry plasma 8 N/A A ±1.47 N/A 51 77 A 0.45 N/A De Luigi, NINCDS- 4 N/ N/ 2001 n n n y n ADRDA ELISA plasma 4 N/A A N/A N/A 12 N/A A N/A N/A De Luigi, NINCDS- 5 N/ N/ 2002 y n n y n ADRDA ELISA plasma 8 N/A A N/A N/A 47 N/A A N/A N/A Dekosky, NINCDS- 2003 ADRDA, 3 17.17 28.83 DSM-III- 5 74.19 29 ± 11 68.34 36 ± y n n y y R RIA plasma 9 ± 0.42 % 0.29 N/A 3 ± 0.89 % 0.11 N/A NINCDS- Devcic, ADRDA, 5 80.9 ± N/ 15.6 10 56.52 N/ 27.4 2014 y n n n y DSM IV ELISA serum 5 6.4 A ± 4.4 N/A 4 ± 7.22 A ± 1.7 N/A Diniz, NINCDS- 3 75.8 ± 39 19.4 69.1 ± 17 29 ± 2010 n n n n n ADRDA ELISA serum 1 6.6 % ± 3.6 N/A 64 5.6 % 1 N/A Dursun, 7 70.29 N/ 16.8 66.49 N/ 28.7 2015 y n n y y DSM-IV ELISA plasma 4 ± 7.26 A ± 5.2 N/A 53 ± 8.45 A ± 1.5 N/A Dziedzic, NINCDS- whole 1 56 58 2003 n n y n y ADRDA ELISA blood 8 62.4 % 9 - 20 N/A 12 64.3 % ≥28 N/A 1 Edwards, NINCDS- Multiplex 2 76.1 ± 29 13 71.2 ± 31 2014 n n n n n ADRDA Assay serum 9 8.6 % N/A N/A 7 9.2 % N/A N/A 17.9 El Sayed, NINCDS- 6 71.1 ± 46 +/1 69.8 ± 60 28.4 2009 y y y n n ADRDA ELISA serum 5 3.2 % 3.8 N/A 20 3.1 % ±2.7 N/A Eriksson, 25.2 2011 NINCDS- 9 81.6 ± 20 24 ± 20 81.3 ± 38 ± n n n n n ADRDA ELISA serum 7 5.3 % N/A 3.1 5 5.6 % N/A 4.3 Faria, NINCDS- 5 76.2 ± 34 74.3 ± 23 2014 y n y y n ADRDA ELISA plasma 0 5.7 % N/A N/A 56 5.7 % N/A N/A Fenoglio, 1 28.35 2004 NINCDS- 2 75 ± N/ 16.8 71.5 ± N/ ± y n n n n ADRDA ELISA serum 2 9.73 A ± 4.7 N/A 83 10.28 A 0.61 N/A Fillit, NINCDS- 2 N/ N/ 1991 y n n n n ADRDA ELISA serum 4 N/A A N/A N/A 9 N/A A N/A N/A Fischer, NINCDS- Immunoradio 1997 ADRDA, metric Assay, 4 79.9 ± N/ 7.5 ± 79.5 ± N/ 27.9 y n y y n DSM-II-R RIA plasma 1 10.3 A 7.8 N/A 19 9.1 A ± 1.4 N/A Forlenza, NINCDS- 5 76.3 ± 17 19.3 69.09 35 29.2 2009 n n n n n ADRDA ELISA serum 8 6.5 % ± 3.7 N/A 31 ± 6.7 % ± 1.0 N/A Galimber 18.6 28.8 ti, 2006 NINCDS- 9 79.1 ± 26 ± 71.5 ± 29 ± y n n n n ADRDA ELISA serum 4 0.72 % 1.23 N/A 24 2 % 1.20 N/A Geppert, NINCDS- 2010 ADRDA, DSM-III- 2 59 N/ y n y n n R ELISA plasma 2 63.54 % N/A N/A 19 N/A A N/A N/A Gezen- 7 70.42 N/ 16.9 67.24 N/ 28.7 Ak, 2013 y n n y y DSM-IV ELISA serum 6 ± 3.73 A ± 5.1 N/A 50 ± 8.20 A ± 1.5 N/A Gubandr ELISA, 2 80.73 52 78.07 50 u, 2013 n n n n n N/A Immunoassay serum 1 ± 5.70 % N/A N/A 10 ± 5.61 % N/A N/A Hare, Immunoturbidi 3 66.8 ± 50 74 ± 50 2016 y y n n n N/A metric Assay plama 6 4.8 % N/A N/A 34 7.1 % N/A N/A NINCDS- Hernanz, ADRDA, 2 73.2 ± 40 73.5 ± 50 2007 n n n n n DSM IV ELISA, HPLC serum 5 7.1 % N/A N/A 44 3.2 % N/A N/A NINCDS- ADRDA, Hertze, DSM-III- 9 35 19 ± 24 ± 22 29 ± 27 ± 2014 n n n n n R ELISA, RIA plasma 2 76 ± 7 % 4 4 72 75 ± 7 % 2 5 Huang, DSM-IV- 2 73.1 ± 50 17.5 63 ± 68 2012 n n n n n TR ELISA plasma 8 9.4 % ± 5.9 N/A 19 5.6 % N/A N/A Huang, NINCDS- 3 71.7 ± 42 73.3 ± 41 2013 y y n n n ADRDA ELISA serum 1 8.2 % N/A N/A 29 7.5 % N/A N/A Huang, NINCDS- 1 2016 ADRDA, 1 75.18 46 15.6 73.2 ± 56 26.3 y n n y y DSM IV ELISA plasma 0 ± 6.71 % ± 6.2 N/A 50 6.2 % ± 2.1 N/A Johansso 23 23.4 23.8 n, 2013 3 74.33 47 (19- ± 74.33 50 28.5 ± y n n n n DSM-IV ELISA serum 2 ± 4.66 % 25) 0.87 20 ± 6.38 % ± 0.5 0.7 Johnston, 1 25.6 2014 NINCDS- 1 58 23.6 ± 75.2 ± 52 28.9 27 ± n n n n n ADRDA Immunoassay plasma 2 75 ± 8 % ± 1.9 3.8 58 5.8 % ± 1.1 4.1 Juraskov 1 a, 2010 2 33 24 n n n n n N/A ELISA serum 9 80 % N/A N/A 58 83.5 % N/A N/A Kalman, NINCDS- 1997 ADRDA, 28.6 DSM-III- 4 73.46 37 9.8 ± 72.9 ± 25 ± y y n y n R ELISA serum 1 ± 6.48 % 8.0 N/A 24 4.27 % 1.47 N/A Kamer, NINCDS- 29.3 2009 ADRDA, 1 N/ 19.5 N/ ± n n y n n DSM IV Immunoassay plasma 8 N/A A ± 5.2 N/A 16 N/A A 0.77 N/A 22.0 23.4 Khemka, 6 66.97± 53 10.27 2 ± 64.75 57 29.10 8 ± 2014 y y y n n DSM-IV ELISA serum 0 6.36 % ±3.77 2.20 60 ± 4.40 % ±.72 1.59 Kim, NINCDS- 22.7 24.7 2011 ADRDA, 1 75.9 ± 50 15.9 ± 75.5 ± 48 27.9 ± n n n n n DSM-IV ELISA plasma 8 6.0 % ± 6.1 2.3 21 1.3 % ± 1.6 2.0 Kim, DSM-IV- 2 74.8 ± 70 18 ± 74.8 ± 67 26.5 2012 n n n y n TR ELISA serum 0 6.4 % 4.9 N/A 18 6.7 % ± 1.5 N/A Kim, 15.3 22.2 27.77 23.3 2015 DSM-IV- 4 76.94 18 ± ± 74.08 42 ± 4 ± n n y y y TR ELISA serum 9 ± 6.80 % 3.65 2.6 26 ± 4.15 % 1.63 3.04 Kim, NINCDS- 5 N/ N/ 2016 n n y n n ADRDA ELISA serum 6 N/A A N/A N/A 24 N/A A N/A N/A Kizilarsl NINCDS- angolu, ADRDA, 3 79.86 50 26.7 74.22 34 26.7 2015 n n n y y DSM-IV ELISA serum 8 ± 5.55 % N/A ±3.4 32 ± 7.21 % N/A ±2.9 Laske, NINCDS- 2008 ADRDA, 3 70.5±8 40 23.6± 69.9±1 67 28.4 n n y n n DSM-IV ELISA plasma 0 .2 % 1.6 N/A 30 1.1 % ±1.6 N/A NINCDS- Laske, ADRDA, 5 72.1 ± 40 23.0 69.4 ± 50 28.7 2009 y n y n n DSM-IV ELISA plasma 0 8.0 % ± 3.2 N/A 50 10.3 % ± 1.3 N/A Laske, NINCDS- 6 71.7 ± 38 20.4 70.0 ± 48 29.2 2011 y n y n n ADRDA ELISA serum 5 8.3 % ± 4.2 N/A 50 8.1 % ± 0.8 N/A Laske, NINCDS- 4 72.4 ± 43 23.1 71.8 ± 50 28.7 2013 y n y y n ADRDA ELISA serum 0 8.2 % ± 3.0 N/A 40 3.7 % ± 0.9 N/A RIA, 18.06 27.53 Lawlor, NINCDS- Immunonephel 1 74.94 29 ± 68.47 20 ± 1996 n n n y n ADRDA ometry serum 7 ± 5.34 % 4.71 N/A 15 ± 6.84 % 1.25 N/A Lee, ELISA, 25.0 25.0 2008 NINCDS- Multiplex 1 82.7 ± 30 ± 71.4 ± 32 ± n n y n y ADRDA ELISA plasma 0 8.4 % N/A 6.1 19 5.3 % N/A 4.1 Lepara, Immunoassay, 4.53 23.7 28.33 25.3 2009 NINCDS- Immunonephel 3 79.96 67 ± 1 ± 77.53 87 ± 1 ± y n n y n ADRDA ometry serum 0 ± 0.95 % 0.62 1.03 30 ± 0.96 % 0.25 0.54 MMSE, ADAS- Cog, 1 20.37 Leung, CERAD, Multiplex 1 76.2 ± 33 ± 11 72.3 ± 46 29 ± 2013 n n n n n CDR ELISA plasma 7 6.09 % 4.68 N/A 2 6.72 % 1.21 N/A NINCDS- Leyhe, ADRDA, 1 70.8 ± 21 23.5 68 ± 42 28.5 2009 n n y n n DSM-IV ELISA plasma 9 2.0 % ± 0.4 N/A 45 1.5 % ± 0.2 N/A NINCDS- ADRDA, Licastro, DSM-III- 3 70.8 ± N/ N/ 1995 n n y y n R ELISA, RIA serum 0 3.8 A N/A N/A 16 76 ± 1 A N/A N/A NINCDS- Licastro, ADRDA, 1 36 12 ± 60 26 ± 1996 n n n y y DSM-II-R ELISA, RIA serum 1 75 ± 2 % 0.6 N/A 10 77 ± 3 % 0.7 N/A NINCDS- ADRDA, Licastro, DSM-III- 2 N/ N/ 1997 n n y y n R ELISA, RIA serum 0 73 ± 1 A N/A N/A 10 75 ± 3 A N/A N/A Licastro, NINCDS- 2000a ADRDA, 1 DSM-III- 1 N/ 14 ± 14 N/ n n n n n R ELISA plasma 8 74 ± 1 A 0.8 N/A 4 83 ± 1 A >26 N/A Licastro, NINCDS- 2000b ADRDA, 1 DSM-III- 4 37 15 ± 39 n n n y n R ELISA plasma 5 75 ± 1 % 1 N/A 51 78 ± 2 % >26 N/A Licastro, NINCDS- 2001a ADRDA, 1 DSM-III- 1 N/ 15 ± 14 N/ n n n y n R ELISA, RIA plasma 5 75 ± 1 A 1 N/A 0 82 ± 2 A >26 N/A Licastro, NINCDS- 2001b ADRDA, DSM-III- 1 55 10 ± 18 n n n y y R RIA N/A 1 78 ± 2 % 2 N/A 11 74 ± 2 % <26 N/A Licastro, NINCDS- 2003 ADRDA, 3 DSM-IV- 3 33 39 76 ± 22 n n n n n R ELISA plasma 2 71±8 % N/A N/A 3 14 % N/A N/A Lieberma DSM-III- 5 46 70 ± 57 n, 1995 n n n n n R RIA serum 7 80 ± 8 % N/A N/A 67 10 % N/A N/A Lindberg NINCDS- 28.8 , 2005 ADRDA, 1 73.6 ± 33 8.5 ± 58.1 ± 55 ± n n y y n DSM-IV ELISA serum 2 2.45 % 0.91 N/A 11 2.23 % 0.26 N/A Liu, NINCDS- 5 68.57± 50 10 71.18± 55 2016 n n n n n ADRDA Immunoassay serum 6 10.84 % N/A N/A 0 10.77 % N/A N/A 1 Llano, NINCDS- Multiplex 0 74.6 ± 58 23.6 75.1 ± 52 28.9 2013 n n n n n ADRDA ELISA plasma 9 8 % ± 1.9 N/A 58 5.8 % ± 1.2 N/A Maes, 1 78.4 ± 20 75.6 ± 53 1999 y n y n n DSM-IV ELISA serum 5 10.3 % <16 N/A 15 9.1 % N/A N/A NINCDS- Malaguar ADRDA, 12.8 nera, DSM-IV- 4 73.2 ± 40 ± 73.5 ± 50 29.7 2006 n n n y y R ELISA plasma 0 7.08 % 3.02 N/A 30 3.24 % ± 0.4 N/A Mancinel fribrino la. 2009 gen - NINCDS- Immunonephel plasma, ADRDA, ometry, Clauss CRP - 6 83.4 ± 66 83.01 35 n n n y n DSM-IV Method serum 4 0.87 % N/A N/A 99 ± 0.6 % N/A N/A Mansoori NINCDS- , 2010 ADRDA, 7 66.4 ± 68 17.2 64.0 ± 64 n n n n n DSM-IV ELISA serum 4 9.2 % ± 4.6 N/A 13 8.4 % >24 N/A 18.8 Markstei NINCDS- 9 77 ± 42 +-/- 72.1 ± 47 28.4 ner, 2011 n n n n n ADRDA ELISA plasma 6 0.8 % 0.6 N/A 19 1.3 % ± 0.3 N/A 25.5 26.2 Markstei NINCDS- Multiplex 3 36 20 ± ± 71 ± 57 29 ± ± ner, 2014 n n y y n ADRDA ELISA plasma 3 81 ± 1 % 0.8 5.9 23 1.4 % 0.2 6.3 Mateo, NINCDS- 5 57 79.8 ± 45 2007 y y n n n ADRDA ELISA serum 1 78 ± 6 % N/A N/A 66 8.1 % N/A N/A Matsubar NINCDS- RIA, Laser 2 40 52.7 ± 40 a, 1989 n n n n n ADRDA Nephelometry serum 0 80.3 % N/A N/A 77 14.76 % N/A N/A Matsubar NINCDS- 3 45 43 a, 1990 n n n n n ADRDA RIA serum 8 76.1 % N/A N/A 89 57.2 % N/A N/A NINCDS- 1 McIlroy, ADRDA, 0 78 ± 33 10 78.3 ± 33 2000 y y n n n DSM-IV RIA serum 8 6.1 % 15.2 m 8 5.9 % ≥29 N/A Mizrahi, NINCDS- 6 74.1 ± 45 17.7 74.6 ± 45 28.8 2003 y y n n n ADRDA Immunoassay plasma 4 7.9 % ± 6.8 N/A 64 6.9 % ± 1.1 N/A Mocali, NINCDS- 1 73.5 ± N/ 70 ± N/ 2004 y n n y n ADRDA Western Blot plasma 8 7.04 A N/A N/A 40 4.5 A N/A N/A Motta, NINCDS- 5 72.2 ± 47 15.7 72.5 ± 50 29.6 2007 n n n y y ADRDA, ELISA plasma 1 6.91 % ± 2.7 N/A 20 2.38 % ± 0.5 N/A DSM-IV- R Nagao, NINCDS- 2 78.4 ± 37 33 78.4 ± 33 1992 n n n n y ADRDA RIA serum 7 4.8 % N/A N/A 3 6.3 % N/A N/A NINCDS- 2 28.5 Nielsen, ADRDA, 6 71 ± 32 19 ± 72.75 38 ± 2007a n n n n n DSM-IV ELISA plasma 0 25.34 % 4.9 N/A 34 ± 6.46 % 0.95 N/A ELISA, Multiplex ELISA, NINCDS- Rocket 2 Nielson, ADRDA, Immunoelectro 5 74.7 ± 33 21.4 72.4 ± 38 29.1 2007b y n n n n DSM phoresis plasma 8 6.3 % ± 5.0 N/A 37 7.5 % ± 1.0 N/A 1 29.3 O'Bryant NINCDS- Multiplex 9 75.8 ± 50 20.7 17 70.7 ± 86 ± , 2010 n n n n n ADRDA Immunoassay serum 2 8.2 % ± 5.6 N/A 4 8.2 % 0.91 N/A serum O'Bryant NINCDS- Electrochemilu & 7 76.1 ± 30 19.1 71.2 ± 32 29.6 , 2016 n n y n n ADRDA minescence plasma 9 8.6 % ± 6.4 N/A 65 9.2 % ± 0.7 N/A Ozturk, NINCDS- 2 77.7 ± 31 10.9 64.7 ± 48 24.5 2007 n n y n n ADRDA ELISA plasma 9 8.3 % ± 7.0 N/A 23 8.5 % ± 1.7 N/A Mass spectroscopy, 17.92 24.24 Park, NINCDS- Immunoturbidi 8 77.83 46 ± 11 69.93 42 ± 2014 n n n n n ADRDA metric Assay serum 9 ± 6.65 % 5.08 N/A 8 ± 5.89 % 3.84 N/A NINCDS- ADRDA, ELISA, 1 25.5 28.7 Porcellin DSM-IV- Immunonephel 9 79.17 25 16.3 ± 83 46 28 ± ± i, 2008 n n n n n R ometry plasma 5 ± 8.3 % ± 5.9 4.9 0 73 ± 6 % 1 4.5 NINCDS- ADRDA, 2 Porcellin DSM-III- 9 75.14± N/ 14 71.64± N/ i, 2013 n n n n n R ELISA plasma 1 7.97 A N/A N/A 8 4.70 A N/A N/A 2 Qin, NINCDS- Antibody 0 71.1 ± 55 26 72.3 ± 23 2015 y y n n n ADRDA Assay plasma 5 7.9 % N/A N/A 2 7.3 % N/A N/A NINCDS- Reale, ADRDA, 3 73.8 ± 53 19.2 72.7 ± 46 25.7 2012 n n n n n DSM ELISA plasma 8 5.5 % ± 3.9 N/A 39 4.8 % ± 3.2 N/A 1 Rembach NINCDS- Mass 8 74 ± 42 16.7 69 70 ± 31 28.8 , 2013 n n n n n ADRDA spectroscopy serum 6 9.4 % ± 7.0 N/A 5 6.9 % ± 1.3 N/A NINCDS- Rentzos, ADRDA, 2 61.5 ± 60 60.8 ± 67 2004 n n n n n DSM ELISA serum 5 8.7 % N/A N/A 15 8.9 % N/A N/A Rentzos, NINCDS- 2 45 20.2 53 29.3 2007 n n n y y ADRDA ELISA serum 0 74 ± 7 % ± 2.4 N/A 15 70 ± 8 % ± 0.3 N/A 20.43 21.14 Richards NINCDS- 6 79.62 57 ± 75.56 37 ± on, 2013 n n n y y ADRDA ELISA serum 6 ± 6.48 % 4.07 N/A 35 ± 7.61 % 4.33 N/A 8 Ritchie, Immunoturbidi 2 78 ± 365 16 78 ± 37 2016 y y n n n DSM-IV metric Assay N/A 1 5.94 0% N/A 40 5.94 % N/A N/A Rodrigue z- Rodrigue NINCDS- 6 76.1 ± 21 80.7 ± 17 z, 2007 y y n n n ADRDA ELISA serum 3 8.1 % N/A N/A 77 7.7 % >28 N/A NINCDS- Rota, ADRDA, 3 71 ± 40 16 ± 69 ± 60 29 ± 2006 n n n y n DSM-IV RIA serum 0 6.03 % 4.36 N/A 25 8.60 % 0.84 N/A Sandwich Rubio- chemiluminesc Perez, NINCDS- ent 4 76.5 ± 27 23 2013 n n n y n ADRDA immunoassay serum 8 3.5 % <23 N/A 52 79±4 % >26 N/A NINCDS- Scacchi, ADRDA, Immunonephel 8 86.1 ± 24 15 83.8 ± 42 2001 n n n n n DSM-III ometry plasma 5 3.8 % N/A N/A 6 3.2 % N/A N/A Scacchi, NINCDS- Immunonephel 9 85.8 ± 24 15 83.9 ± 41 2002 y n n n n ADRDA ometry serum 3 3.8 % N/A N/A 7 3.1 % N/A N/A Shibata, NINCDS- 1 70.5 ± N/ 69.1 ± N/ 2002a n n n n n ADRDA ELISA plasma 5 9.6 A N/A N/A 26 9.4 A N/A N/A Shibata, NINCDS- 1 N/ N/ 2002b y n n n n ADRDA ELISA plasma 6 N/A A N/A N/A 13 N/A A N/A N/A Singh, NINCDS- 2 73 ± 45 64 ± 29 1997 y y n n n ADRDA ELISA plasma 2 10 % N/A N/A 17 13 % N/A N/A 20.71 25.5 29.38 26.5 Smith, NINCDS- 3 77.1 ± 50 ± ± 76.6 ± 50 ± ± 2011 y n n n n ADRDA ELISA plasma 4 6.8 % 2.58 5.1 34 6.0 % 0.65 7.1 NINCDS- 21.6 22.2 Solerte, ADRDA, 2 76.5 ± 45 ± 40 ± 2000 n n n n n DSM-III ELISA Serum 2 5.5 % 6-16 1.2 15 77 ± 6 % N/A 1.5 5 17.63 28.86 Song, NINCDS- Blood 3 75.86 38 ± 11 74.47 68 ± 2015b n n n n y ADRDA measurements serum 2 ± 7.94 % 5.68 N/A 9 ± 9.4 % 1.19 N/A NINCDS- Sousa, ADRDA, 5 76.2 ± 34 74.3 ± 26 2014 n n n n n DSM-IV ELISA plasma 0 5.7 % N/A N/A 50 5.7 % N/A N/A Spectrophotom NINCDS- etry, Squitti, ADRDA, Immunoturbidi 4 75.6 ± 26 18.6 71.1 ± 55 28.1 2005 n n n y n DSM metric Assay serum 7 7.7 % ± 4.7 N/A 44 11 % ± 1.3 N/A 73.67 Squitti, NINCDS- Spectrophotom 2 ± N/ 19 ± 76.1 ± N/ 28 ± 2008 y y n n n ADRDA etry serum 5 12.58 A 5 N/A 25 6.4 A 1 N/A Sun, NINCDS- 6 70.1 ± 28 22.6 68.9 ± 46 29.6 2014 y n y n n ADRDA Western Blot plasma 4 8.9 % ± 3.6 N/A 50 6.8 % ± 0.6 N/A Talebi, 4 72.1 ± 48 70.8 ± 48 2008 y y n n n DSM ELISA serum 0 7.9 % N/A N/A 40 7.7 % N/A N/A Dementia with Tarkows instrument 3 63 ± 41 65 ± N/ ki, 1999 n n n n n al deficits ELISA serum 4 5.83 % N/A N/A 25 10 A N/A N/A Tarkows NINCDS- ELISA, Bio- 89 N/ ki, 2001 n n n n n ADRDA assay serum 9 63 ± 3 % N/A N/A 30 N/A A N/A N/A 22.0 22.6 Teixeira, NINCDS- 4 75.4 ± 34 17.9 ± 68.7 ± 20 28.9 ± 2013 n n n n n ADRDA ELISA serum 1 7.9 % ± 4.2 32.2 51 5.6 % ± 1.4 3.2 NINCDS- ADRDA 20.24 28.41 Teunisse and DSM- 3 73 ± 41 ± 68 ± 57 ± n, 2003 n n y y n IV ELISA serum 4 10 % 4.975 N/A 61 6.7 % 1.697 N/A 1 Teunisse 0 51 19 ± 24 ± 60 25 ± n, 2015 y n y n n N/A RIA serum 0 63 ± 6 % 5 3 65 58 ± 7 % N/A 2 ELISA, Thambis Western Blot, etty, NINCDS- Quantitative 7 76.0 ± 35 20.9 73.1 ± 45 29 ± 2011 n n n n n ADRDA Immunoassay plasma 9 6 % ± 4.6 N/A 95 7 % 1.2 N/A Theodor 27.1 28.1 opoulou, NINCDS- 2 72.61 37 11.3 ± 68.16 43 ± 2012 y n y y n ADRDA RIA serum 7 ± 4.68 % ± 9.7 4.0 23 ± 7.20 % N/A 4.2 1 Tisato, Colorimetric 6 79 ± 27 73.33 32 2016 n n y n y N/A Method plasma 5 5.98 % N/A N/A 56 ± 9.13 % N/A N/A 24.6 25.5 Uslu, NINCDS- 2 68.39 36 19 ± 8 ± 66.17 38 26.25 6 ± 2012 n n n n n ADRDA ELISA serum 8 ± 6.74 % 1 4.03 26 ± 9.45 % ± 1.1 2.33 Van Duijn, NINCDS- 9 N/ N/ 1990 y y n n n ADRDA Bio-assay serum 7 N/A A N/A N/A 79 N/A A N/A N/A 1 Villarreal NINCDS- Multiplex 3 81.9 ± 46 16.2 76.5 ± 35 28.3 , 2016 n n n n n ADRDA Assay serum 5 9.2 % ± 4.0 N/A 77 6.7 % ± 1.8 N/A ELISA, 18.65 27.0 28.58 28.7 Vurgun, NINCDS- Immunonephel 4 33 ± 2 ± 30 ± 6 ± 2013 n n n n n ADRDA ometry serum 0 N/A % 7.49 4.16 40 N/A % 1.55 5.30 Wang, 1 64 54 2002 n n y n n N/A ELISA serum 1 59-74 % N/A N/A 13 51-77 % N/A N/A 3 Wang, NINCDS- 9 74.1 ± 28 11 68.9 ± 36 2002b n n y n n ADRDA RIA plasma 7 8.9 % N/A N/A 8 9.3 % N/A N/A NINCDS- Wang, ADRDA, 9 73.7 ± 56 17.8 73.7 ± 46 28.5 2014 n n y n n DSM-IV ELISA plasma 7 9.4 % ± 7.5 N/A 22 8.4 % ± 1.3 N/A 21.3 22.6 Waragai, 6 78.8 ± 33 18.9 ± 76.0 ± 55 28.0 ± 2016 y n n n n N/A ELISA serum 3 6.1 % ± 2.4 3.8 62 7.9 % ± 2.3 2.2 1 19.21 18.8 29.42 19.9 Warren, NINCDS- 4 77.38 45 ± ± 19 70.42 63 ± ± 2012 n n n n n ADRDA N/A serum 8 ± 8.3 % 6.22 4.7 8 ± 8.89 % 0.88 4.8 1 20.5 21.9 Watanab NINCDS- Radioimmuno 0 76 11 ± ± 22 76 ± 56 28 ± ± e, 2005 y y n n n ADRDA assay serum 6 79 ± 7 % 7 2.9 7 10 % 1 4.2 Fluorescein Xue, NINCDS- isothiocyanate 5 74.5 ± 64 16.9 71.7 ± 60 29.4 2012 y y y y n ADRDA antibodies plasma 6 9.8 % ± 2.8 N/A 20 8.9 % ± 0.5 N/A serum Yamamo NINCDS- Immunonephel and 6 31 13 ± 21 ± 53 27 ± 22 ± to, 2005 y y n y n ADRDA ometry plasma 1 80 ± 6 % 8 3 32 77 ± 5 % 2 3 NINCDS- ADRDA, 1 Yang, DSM-III- Radioimmuno 1 73.2±2 52 12 74.3±2 52 2009 y y n n n R assay serum 2 .5 % N/A N/A 1 .8 % N/A N/A 2 Yarchoa 0 74.5 ± 42 22.8 11 69.9 ± 32 28.9 n, 2013 n n n n n N/A ELISA plasma 3 7.7 % ± 4.5 N/A 7 10.1 % ± 1.5 N/A 6.88 Yasutake NINCDS- 6 77.93 33 ± 71.1 ± 24 , 2006 y y n n n ADRDA ELISA serum 0 ± 7.04 % 6.78 N/A 33 5.8 % N/A N/A NINCDS- ADRDA, 1 64 54 Yu, 2005 n n y n n DSM-IV ELISA serum 1 59-74 % N/A N/A 13 55-76 % N/A N/A NINCDS- 13.52 28.15 ADRDA, Multiplex 5 76.42 60 ± 77 ± N/ ± Yu, 2016 y y y n n DSM-IV Assay serum 0 ± 8.88 % 5.75 N/A 40 7.46 A 1.73 N/A 27.6 25.8 Zaciragic NINCDS- Immunonephel 1 73.46 N/ 2 ± 69.93 N/ 6 ± , 2007 y n n y n ADRDA ometry serum 5 ± 9.95 A <23 1.68 15 ± 2.57 A >28 0.98 NINCDS- 1 Zhang, ADRDA, Immunoassay 8 74.23 49 73.6 ± 49 2003 y y n n y DSM-IV kit serum 0 ± 0.53 % N/A N/A 92 0.59 % N/A N/A 1 Zhang, NINCDS- 5 71.6 ± 42 13.5 12 70.2 ± 43 27.0 2013a y n n y y ADRDA ELISA plasma 3 9.2 % ± 6.8 N/A 0 7.1 % ± 2.4 N/A Zhang, NINCDS- 4 77.9 ± 41 24.4 75.4 ± 52 2013b y n n n n ADRDA ELISA plasma 1 7.7 % ± 2.1 N/A 31 9.5 % N/A N/A 22.5 23.9 Zhang, NINCDS- 9 71.7 ± 40 17.2 ± 70.2 ± 43 27.0 ± 2014 n n n n n ADRDA ELISA plasma 0 9.2 % ± 5.0 2.9 20 7.1 % ± 2.4 2.3 Western Blot, Zhu, NINCDS- Chemilumines 2 72.1 ± 46 72.7 ± 55 2015 n n n n n ADRDA cence serum 6 6.1 % N/A N/A 42 5.3 % N/A N/A Zuliani, NINCDS- 6 78.5 ± 35 16.4 72.3 ± 55 27.4 2007 n n n n n ADRDA ELISA serum 0 7.6 % ± 5.8 N/A 42 5.8 % ± 2.9 N/A Zuliani, NINCDS- 6 78.5 ± 35 16.4 74.5 ± 53 28.8 2008 n n n n n ADRDA ELISA plasma 0 7.6 % ± 5.8 N/A 30 5.1 % ± 2.9 N/A Zuliani, NINCDS- HPLC, Mass 6 78 ± 22 21.3 73 ± 33 28 ± 2011 n n n n n ADRDA spectroscopy plasma 0 5.5 % ± 3.8 N/A 40 8.7 % 2 N/A

*MMSE scores were reported out of a maximum score of 35

Legend: AD = Alzheimer's Disease. NINCDS-ADRDA = National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association, DSM = Diagnostic and Statistical Manual. ELISA = enzyme-linked immunosorbent assay. HPLC = High Performance Liquid Chromatography. RIA = Radial Immunodiffusion Assay. n = no, y = yes, N/A = not available

Supplementary Table 3. Study quality and risk of bias assessment. Study quality was assessed using items from the Newcastle Ottawa Scale and the Cochrane Collaboration’s risk of bias assessment tool, addressing key methodological criteria relevant to

included studies.

trols

phicsreported

retrospective design retrospective

-

community con community

ADRDA or DSM criteria used DSM or ADRDA criteria

-

similarly aged controls aged similarly

demogra

excluded use of NSAIDs of use excluded

reported medication use reported

non

representative population representative

similar in other characteristics in similar other

medical comorbidities reported comorbidities medical

cognitively intact control group control intact cognitively

excluded medical comorbidities medical excluded

likelihoodquality high of overall

assessed for cognitive impairment cognitive for assessed

similar gender proportions in proportions controls gender similar NINCDS

Al-khateeb, 2014 + - - + + - - + + - + + + + + Al-khateeb, 2015 + - + + + - + + + - + + + + + Alsadany, 2012 + + - + + - + + + + + + + + + Altstiel, 1995 + - + + + + + + + ? + ? ? + - Alvarez, 1996 + - + + + + + + + + + + + + + Alvarez, 2007 + - - + + - + + ? + - + - - - Angelopoulos, 2008 - + - + + - - + ? + - ? - - - Araga, 1991 + - - + + - - - + + + + + + + Bai, 2013 + - + + + - + + + + + + - + + Balldin, 2012 + - - + + - - + + + + - - + + Baraczka, 1995 - - - + - - - + + + + ? - - - Baranowska-Bik, 2008 + - - + - - - - ? - + + + + - Baranowska-Bik, 2015 + - + + + - - - + ? + - + + + Belkhelfa, 2014 + - - + ? - + + + + + + + + + Bermejo, 2008 - + + + + + + + ? + + ? ? + + Biella, 2013 + - - + + - - + + + + + + + + Bigalke, 2011 + + + + + + - + + + - + + + + Bjorkqvist, 2012 + - - + + - - + + + + - + + + Blum-Degen, 1995 + + - + + - - + ? + + + + - + Bozluolcay, 2016 + - + + + - - + ? + + + + + + Bonaccorso, 1998 + - + + + - + + + + + - + - + Bonotis, 2008 + - + + + - + + + - + + + + + Borroni, 2002 + - + + + - - + + + + + + + + Cacabelos, 1991 - - + + + - - + + + - ? + + - Cacabelos, 1993 - - - + ? ? - + ? + - ? - + - Cacabelos, 1994 + + + + + - - + + + + + + + + Cestari, 2016 + - + + + - - + + + + + + + + Chakrabarti, 2014 + - + + + - - + + ? + + + + + Chao, 1994a + + - + + - - + ? - + + + + + Chao, 1994b + - - + - - - - ? + ? + ? - - Chen, 2012 + + + + + + + + + + + + + + + Chen, 2014 + + + - + - + + - + + + + + + Chiappelli, 2006 + - - + + - - + + + + - + + + Choi, 2008 + - + + + - + + ? + + + + - + Ciabattoni, 2007 + + + + + - + + + + + + + + + Cojocaru, 2011 + - + + - - - + ? + + + + - - Corsi, 2011 - - - + + - - - + ? + - - + - Davis, 2007 - - - + + - - + + + ? ? - + - Davis, 2009 - - - + + - - + + + ? ? - + - De Luigi, 2001 - - + + + - - + ? + ? ? - + - De Luigi, 2002 - - + + + - - ? ? + - - + + - Dekosky, 2003 + - + + + - + + + + + + + + + Devcic, 2014 + + + + + - + + + + - ? + + + Diniz, 2010 + - - + + + - + + + + - - + + Dursun, 2015 - - + + + - + + + + + ? + + + Dziedzic, 2003 + - + + - + + + + + + + + + Edwards, 2014 + - - + + - - + ? + + - + - + El Sayed, 2009 + - - + + - - + + + + + + + + Eriksson, 2011 + - + + + - - + ? + + - + + + Faria, 2014 + - + + + + + + ? + + - + + + Fenoglio, 2004 + - - + + - - + ? + + - - + - Fillit, 1991 - - + + + - - ? ? + - - - - - Fischer, 1997 + - + + + - - + + + + ? - + + Forlenza, 2009 + - + + + - - + + + - - - + - Galimberti, 2006 + - - + + - - + + + + + + + + Geppert, 2010 + - - + + - - + ? + + ? - + - Gezen-Ak, 2013 + - + + + - + + + + + ? + + + Gubandru, 2013 + + + + - - - + ? ? + + + - - Hare, 2016 + - - + - - - + ?` + + + + - + Hernanz, 2007 + - - + + - - + ? + + + + + ? Hertze, 2014 + + + + + - - + + + + + + + + Huang, 2012 + - - + + - - + - + + + + + + Huang, 2013 + + + + + - - + ? + + + + - + Huang, 2016 + + + + + + + + + + + + + + + Johansson, 2013 + - + + + - - + + + + + + + + Johnston, 2014 + - + - + - - + + + + + + + + Juraskova, 2010 - - + + - - - + - - + - - - - Kalman, 1997 + - - + + - - + + + + + - + + Kamer, 2009 + - + + + - - + + + - - + + + Khemka, 2014 + - + + + - - + + + + + + + + Kim, 2011 + - + - + + - + + + + + - + + Kim, 2012 + - + - + + + + + + + + + + + Kim, 2015 + - + + - + + + + + + - + + + Kim, 2016 - - + + + - - + ? + ? ? ? + - Kizilarslangolu, 2015 + - + + + - + + + + + - + + + Laske, 2008 + - + + + + - - + + + - + + + Laske, 2009 + - + + + - - + + + + + + + + Laske, 2011 + - + + + - - + + + + - + + + Laske, 2013 + - + + + - - + + + + + + + + Lawlor, 1996 + - + + + - - + + - - - + + + Lee, 2008 + - - + + - + + ? + - + + - - Lepara, 2009 + - + + + - - + + + + + + + + Leung, 2013 + - - - + - - + + + + + + + + Leyhe, 2009 + - + + + - - + + + + - + + + Licastro, 1995 - - + + + - - + ? + - ? + + - Licastro, 1996 + - - + + - - + + + + + + + + Licastro, 1997 + - - + + - - + ? + + ? + + + Licastro, 2000a - - - + + - - + + + - ? ? + - Licastro, 2000b + - + + + - - + + + + + + + + Licastro, 2001a + - + + + - - + + ? + ? ? + + Licastro, 2001b + - + + + - - + + ? + ? ? + + Licastro, 2003 + - - + + - - + ? + + - + - - Lieberman, 1995 + + + + + - - - ? ? + + + + + Lindberg, 2005 + - + + + - - + + + - + + + + Liu, 2016 + - + + + - - + + + + + - + - Llano, 2013 + - - + + - - + + + + + + + + Maes, 1999 + - + + + - - + ? + + - + + + Malaguarnera, 2006 + - + + + - + + + + + + + + + Mancinella. 2009 + + + + + + - ? ? ? + + + + + Mansoori, 2010 + - - + + - - + + + + + + + + Marksteiner, 2011 + - - + + - - + + + + + + + + Marksteiner, 2014 + - + + + - - + + - - + + + + Mateo, 2007 + - - + + - - + ? + + - + + + Matsubara, 1989 - - + + + - - - - ? - - - - - Matsubara, 1990 - - + + + - - + ? + - + + - - McIlroy, 2000 - - + + + - - + + + + + + + + Mizrahi, 2003 + - + + + - - + + - + + + + + Mocali, 2004 - - + + + - - + ? + + ? ? + + Motta, 2007 + - - + + - + + + + + + + + + Nagao, 1992 - - + + + - - + + + + - - ? ? Nielsen, 2007a + + - + + + - + + + + + + + + Nielson, 2007b + - - + + + - + + - + + + + + O'Bryant, 2010 + - - + + - - + ? + + + - + - O'Bryant, 2016 + + - + + - - + ? + + - + - + Ozturk, 2007 + - + + + - + + - + - - + + + Park, 2014 + - - + + - - + + + - - + + - Porcellini, 2008 + - - - + - - + + + + + + + + Porcellini, 2013 - - - + + - - + + + + ? + + + Qin, 2015 - - - - + - - ? ? + ? ? ? + - Reale, 2012 + - - + + - - + + + + + + + + Rembach, 2013 + - - + + - - + + + + + + + + Rentzos, 2004 + - - + + - - - ? + + + + + - Rentzos, 2007 + - - + + - + + + + + - + + + Richardson, 2013 + + - + + + + + - + + + + + + Ritchie, 2016 + - - + + + + - + + + Rodriguez-Rodriguez, 2007 + - - + + - - + + - + + + + + Rota, 2006 + - + + + - + + + + + - + + + Rubio-Perez, 2013 + - + + + - - + + + + + + + + Scacchi, 2001 + - - + + - - + ? + + - + + - Scacchi, 2002 + - - + + - - + ? + + + + - + Shibata, 2002a - - - + + - - + ? + + ? ? - - Shibata, 2002b - - - + + - - + + + + ? ? - - Singh, 1997 + - + + + + + + ? + + + + - + Smith, 2011 + + - + + - - + + + + + + + + Solerte, 2000 + - + + + + + + ? + + + + + + Song, 2015b + - + + + - + + + + + + + + + Sousa, 2014 + - - + + + + + + + + + + + + Squitti, 2005 + - + + + - - + + + + - + + + Squitti, 2008 - - + + + - - + + + + ? ? + - Sun, 2014 + - + + + - - + + + + + + + + Talebi, 2008 + - - + + - + + + + + + + + + Tarkowski, 1999 - - + + + - - + ? + + ? ? - - Tarkowski, 2001 - - + + + - - + ? + ? ? ? - - Teixeira, 2013 + + - + + + - + + + - + - + + Teunissen, 2003 + - + + + + - + + + + - + + + Teunissen, 2015 + - + + + - - - + + + + + + - Thambisetty, 2011 + - - - + - - + + + + - + + - Theodoropoulou, 2012 + - + + + - + + ? + + + + + + Tisato, 2016 + + + + - - + + + + + - + + + Uslu, 2012 + - - + + - - + + + + + + + + Van Duijn, 1990 - - - - + - - + + + + + + + + Villarreal, 2016 + + - + + - - + + + - + + + + Vurgun, 2013 + - - + + - - + + + ? + + + + Wang, 2002 - - + + - - - ? + ? + + ? - - Wang, 2002b + - - + + - - + ? + + + + - + Wang, 2014 + - + + + - - + + + + + + + + Waragai, 2016 + - + + - - - + + + + + + + + Warren, 2012 + - - - + - - + + + + + + + + Watanabe, 2005 + + + + + - - + + + + + + + + Xue, 2012 + + + + + + - + + + + + + + + Yamamoto, 2005 + + + + + - - + + + + - + + + Yang, 2009 + - - + + - - + ? + + + + - - Yarchoan, 2013 + - + + + - - + + + + + - + + Yasutake, 2006 + - - + + - - + + + - + + + + Yu, 2005 - - + + + - - + + + + + ? - ? Yu, 2016 + - + + + - - + + + + ? + + + Zaciragic, 2007 - - + + + - - + + + + ? ? + + Zhang, 2003 + - + + + + + + + + + + + + + Zhang, 2013a + - - + + + - - + + + - + + + Zhang, 2013b + - + + + - + + + + + + + + + Zhang, 2014 + + + + + + + + + + + + + + + Zhu, 2015 + - - + + - - + ? + + + ? - - Zuliani, 2007 + + + + + - + + + + + - + + + Zuliani, 2008 + + + + + - + + + + + + + + + Zuliani, 2011 + + + + + - + + + + + + + + + Legend: ‘+’ = characteristic is present. ‘-“ = characteristic not present. ? = could not be assessed.