Background
Methods
Search strategy
Study selection
Data extraction and critical appraisal
Statistical analysis
Results
Demographic features
Study | Year | Participants | Type of study | Gender (M/F) | MMSE | Age | Education (Years) | APOE ε4 status, pos./neg. (% pos.) | Outcome |
---|---|---|---|---|---|---|---|---|---|
Simren et al. [16] | 2020 | 318 | Cross-sectional | C: 46/53 MCI: 51/65 AD: 40/63 | C: 29.07 ± 1.26 MCI: 27.21 ± 1.82 AD: 21.07 ± 4.42 | C: 73 ± 6.14 MCI: 74.47 ± 5.89 AD: 76.35 ± 5.76 | C: 11.23 ± 4.8 MCI: 8.97 ± 4.28 AD: 7.82 ± 3.66 | C: 31/99 (31.3%) MCI: 39/107 (36.4%) AD: 58/103 (56.3%) | Plasma NFL level is increased in AD and MCI groups compared to healthy controls. NFL could be a diagnostic factor due to AD and MCI group changes |
Gerards et al. [17] | 2022 | 111 | Cross-sectional | MCI: 33/24 AD: 24/30 | MCI: 27 ± 2.1 AD: 23 ± 3.6 | MCI: 69.1 ± 9.7 AD: 74.3 ± 8.2 | C: NM MCI: 13 ± 3 AD: 12 ± 2 | NM | Measuring plasma NFL using SIMOA could be a diagnostic factor in AD and MCI groups |
Gleerup et al. [18] | 2021 | 115 | Cross-sectional | C: 11/6 MCI: 25/22 AD: 22/29 | C: 28.9 ± 0.8 MCI: 26.8 ± 3.2 AD: 22.9 ± 4.3 | C: 68.4 ± 8.3 MCI: 71.1 ± 8.2 AD: 72.7 ± 7.5 | NM | NM | There is no correlation between the level of saliva NFL and plasma NFL measured by SIMOA in AD, MCI, and healthy control groups |
Lewczuk et al. [19] | 2018 | 110 | Cross-sectional | C: 22/19 MCI: 10/25 AD: 13/21 | C: 29.3 ± 0.9 MCI: 26.7 ± 2.1 AD: 21.2 ± 3.4 | C: 52.5 ± 13.1 MCI: 71.3 ± 8.4 AD: 70.8 ± 7.6 | NM | NM | Plasma NFL is increased in AD compared to the control group, and plasma NFL could be used as a screening biomarker between groups with cognitively declined function |
Lin et al. [20] | 2018 | 234 | Cross-sectional | C: 31/28 MCI: 27/29 AD: 56/63 | C: 27.8 ± 2.1 MCI: 26.4 ± 2.3 AD: 18.6 ± 6.2 | C: 77.0 ± 6.2 MCI: 77.3 ± 5.1 AD: 76.0 ± 5.6 | C: 12.4 ± 5.0 MCI: 9.5 ± 4.8 AD: 11.0 ± 3.7 | C: 7/59 (12.1%) MCI: 13/56 (23.2%) AD: 42/119 (35.3%) | Plasma NFL may be a potential biomarker in diagnosing AD; NFL is also associated with cognitive status and cognitive function |
Sugarman et al. [21] | 2020 | 579 | Cross-sectional | C: 89/149 MCI: 77/108 AD: 88/68 | C: 29.39 ± 0.91 MCI: 28.20 ± 1.67 AD: 21.11 ± 6.17 | C: 72.38 ± 7.69 MCI: 74.99 ± 7.24 AD: 76.74 ± 8.12 | C: 16.56 ± 2.54 MCI: 15.51 ± 2.74 AD: 14.95 ± 2.95 | C: 77/235 (32.8%) MCI: 59/181 (32.6%) AD: 88/153 (57.5%) | Plasma NFL is a potential biomarker in diagnosing AD and is also very sensitive to cognitive status and decline |
Zhou et al. [22] | 2017 | 578 | Cross-sectional | C: 106/87 MCI: 133/65 AD: 97/90 | C: 29.1 ± 0.99 MCI: 26.9 ± 1.8 AD: 23.3 ± 2.1 | C: 75.7 ± 4.9 MCI: 74.5 ± 7.4 AD: 75.5 ± 7.4 | C: 16.0 ± 2.8 MCI: 15.8 ± 3.0 AD: 14.7 ± 3.1 | NM | Plasma NFL is not an accurate biomarker for diagnosing the early stages of AD |
Hall et al. [23] | 2021 | 546 | Cross-sectional | C: 87/328 MCI: 35/63 AD: 15/18 | C: 26.97 ± 2.59 MCI: 23.92 ± 3.65 AD: 16.98 ± 5.87 | 59.22 ± 6.97 65.61 ± 8.47 73.727 ± 8.80 | C: 8.353 ± 4.30 MCI: 6.370 ± 3.99 AD: 4.818 ± 4.67 | NM | Plasma NFL could be an early diagnostic factor in differentiating MCI and healthy controls in the Mexican–American population |
Wu et al. [24] | 2021 | 428 | Cross-sectional (participants recruited from 2 cohorts) | C: 45/76 MCI: 68/80 AD: 68/91 | C: 29.16 ± 1.12 MCI: 26.33 ± 2.24 AD: 16.66 ± 6.73 | C: 69.3 ± 7.1 MCI: 69.7 ± 8.8 AD: 66.9 ± 9.9 | C: 11.1 ± 3.8 MCI: 11.0 ± 3.9 AD: 8.5 ± 4.4 | C: 13/121 (10.7%) MCI: 58/148 (39.2%) AD: 82/159 (51.6%) | The level of plasma NFL is a reliable diagnostic factor in AD patients in the Chinese population |
Shim et al. [25] | 2022 | 99 | Cross-sectional | MCI: 6/31 AD: 17/45 | MCI: 21.86 ± 3.61 AD: 14.94 ± 5.51 | MCI: 77.14 ± 6.09 AD: 79.39 ± 6.66 | C: NM MCI: 7.46 ± 4.93 AD: 5.92 ± 4.76 | C: NM MCI: 11/34 (32.4%) AD: 13/46 (28.3%) | Plasma NFL level could be used as a possible biomarker in diagnosing AD, and the NFL level is also associated with cognitive decline |
Mattsson et al. [6] | 2017 | 570 | Prospective Case–control | C: 106/87 MCI: 132/65 AD: 94/86 | C: 29.1 ± 1 MCI: 26.9 ± 1.8 AD: 23.2 ± 2.1 | C: 75.9 ± 4.9 MCI: 74.7 ± 7.5 AD: 75.3 ± 7.3 | C: 16.0 ± 2.9 MCI: 15.8 ± 3.0 AD: 14.7 ± 3.1 | C: 50/193 (25.9%) MCI: 103/197 (52.3%) AD: 123/180 (68.3%) | Plasma NFL level is elevated in AD patients as compared to the control group. Hence, plasma NFL is correlated with cognitive decline, and plasma NFL is an accurate biomarker in diagnosing AD |
Parvizi et al. [26] | 2022 | 167 | Cross-sectional | C: 20/24 MCI: 34/29 AD: 24/36 | C: NM MCI: 26.66 ± 2.27 AD: 19 ± 6.83 | C: 62.16 ± 10.49 MCI:69 ± 14.03 AD: 69.36 ± 12,53 | NM | NM | Plasma NFL is a predictive factor in diagnosing AD |
Wang et al. [27] | 2022 | Cohort 1: 40 | Cohort | C: 11/9 AD: 8/12 | C: 28.83 ± 1.59 AD: 15.25 ± 6.98 | C: 56.58 ± 4.98 AD: 56.58 ± 4.18 | C: 10 ± 2.39 AD: 9.08 ± 0.59 | C: 1/20 (5%) AD: 6/30 (30%) | Plasma NFL changes was significant in AD compared to healthy controls |
Wang et al. [27] | 2022 | Cohort 2: 40 | Cohort | C: 9/11 MCI: 7/13 | C: 28.5 ± 2.39 MCI: 25.41 ± 2.59 | C: 56.91 ± 8.17 MCI: 62.41 ± 11.36 | C: 9.25 ± 5.38 MCI: 9.66 ± 3.19 | C: 2/20 (12%) MCI: 7/20 (44%) | MCI group had a higher plasma NFL concentration compared to healthy controls |
Frank et al. [28] | 2022 | 569 | Cross-sectional | C: 87/148 MCI: 86/67 AD: 76/105 | C: 29.39 ± 0.91 MCI: 28.20 ± 1.68 AD: 21.12 ± 6.21 | C: 72.38 ± 7.69 MCI: 74.96 ± 7.25 AD: 76.82 ± 8.13 | C: 16.56 ± 2.54 C: 15.52 ± 2.77 AD: 14.95 ± 2.95 | C: 77/235 (33%) MCI: 60/181 (33%) AD: 89/153 (58%) | In AD diagnosis, elevated plasma NFL concentration was correlated with a higher conditional odds ratio. In contrast, NFL concentration was not associated with an MCI diagnosis |
Asken et al. [29] | 2022 | Cohort1: 50 | Cross-sectional | NM | NM | NM | NM | NM | Plasma NFL concentration in MCI was lower compared to control group |
Asken et al. [29] | 2022 | Cohort2: 71 | Cross-sectional | NM | NM | NM | NM | NM | AD patients had lower level of NFL compared to MCI patients |
Characteristics of the included studies
NFL plasma concentration in MCI vs control
NFL plasma concentration in AD vs control
NFL plasma concentration in MCI vs AD
Risk of bias across studies
Study name | Q1 | Q2 | Q3 | Q4 | Q5 | Q6 | Q7 | Q8 | Yes % | Risk of bias |
---|---|---|---|---|---|---|---|---|---|---|
Hall et al. | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | 100% | Low |
Simren et al. | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | 100% | Low |
Gerards et al. | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | 100% | Low |
Shim et al. | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | 100% | Low |
Gleerup et al. | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | 100% | Low |
Lewczuk et al. | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | 100% | Low |
Lin et al. | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | 100% | Low |
Sugarman et al. | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | 100% | Low |
Wu et al. | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | 100% | Low |
Zhou et al. | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | 100% | Low |
Frank et al. | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | 100% | Low |
Parvizi et al. | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | 100% | Low |
Asken et al. | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | 100% | Low |
Study | Q1 | Q2 | Q3 | Q4 | Q5 | Q6 | Q7 | Q8 | Q9 | Yes % | Risk of bias |
---|---|---|---|---|---|---|---|---|---|---|---|
Mattsson et al. | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | 100% | Low |
Study | Q1 | Q2 | Q3 | Q4 | Q5 | Q6 | Q7 | Q8 | Q9 | Q10 | Q11 | Yes % | Risk of bias |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Wang et al. | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | No | No | Yes | 81% | Low |