Blood Neurofilament Levels Predict Cognitive Decline across the Alzheimer’s Disease Continuum
Abstract
:1. Introduction
2. Results
2.1. Baseline Demographic, Clinical, and Plasma Biomarker Characteristics
2.2. Baseline Plasma NfL Concentration and Association with Cognitive Profile
2.3. Plasma NfL Concentration Predicts Cognitive Decline but Not Conversion to Dementia
2.4. Baseline Plasma NfL Concentration Is Associated with Regional Changes in Brain Volume
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. Ethics Approval and Consent to Participate
4.3. Plasma and CSF Sampling and Analysis
4.4. MRI Examination
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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All | AD | aMCI | naMCI | Anova | |
---|---|---|---|---|---|
Demographic characteristics | n = 350 | n = 161 | n = 141 | n = 48 | p |
Age (years) | 76.8 (6.4) | 75.9 (7.6) | 77.9 (5.3) | 76.4 (4.5) | 0.024 |
Women (%) | 208 (59) | 59.6 (96) | 55.3 (78) | 70.8 (34) | 0.167 |
BMI (kg/m2) | 24.8 (3.9) | 25.1 (4.4) | 24.7 (3.5) | 24.3 (3.6) | 0.410 |
1 or 2 APOE4 alleles (%) | 152 (43) | 50.3 (78) | 43.3 (61) | 27.1 (13) | 0.017 |
Cognitive biomarkers | |||||
MMSE (/30) | 24.6 (3.8) | 22.2 (3.5) | 26.2 (2.7) ** | 27.8 (1.9) ** | <0.0001 |
Brain morphological biomarkers | |||||
Hippocampal volume (R 1 L) (cm3) | 4.3 (1.2) | 3.9 (1.26) | 4.61 (1.19) ** | 5.06 (0.68) ** | <0.0001 |
Blood biomarkers | |||||
Creatinine (μmol/L) | 78.8 (22.7) | 79.8 (25.2) | 78.8 (21.5) | 75.3 (16.9) | 0.449 |
eGFR (mL/min/1.73 m2) | 77.2 (15.5) | 76.7 (16.1) | 77.6 (15.6) | 77.3 (12.8) | 0.414 |
Plasma Aβ1-40 (ng/L) | 270.3 (63.4) | 261.5 (68) | 279.2 (61.3) | 275.5 (47.9) | 0.038 |
Plasma Aβ1-42 (ng/L) | 37.9 (11.5) | 36.7 (11.4) | 38.6 (12.1) | 39.9 (10) | 0.018 |
Plasma Aβ1-42/Aβ1-40 ratio | 0.142 (0.04) | 0.144 (0.04) | 0.14 (0.04) | 0.146 (0.034) | 0.097 |
Plasma NfL (ng/L) | 21.3 (17.4) | 23.1 (22.7) | 20.7 (12) * | 17.1 (6.1) * | 0.009 |
CSF biomarkers | |||||
CSF Aβ1-40 (ng/L) | 7262.9 (2342.4) | 6601.5 (268.3) | 7913.8 * (278.9) | 7126.9 * (527.3) | 0.03 |
CSF Aβ1-42 (ng/L) | 680.8 (362.7) | 556.8 (37.9) | 777.6 (39.1) | 792.0 (74.3) | 0.01 |
CSF Aβ1-42/Aβ1-40 ratio | 0.095 (0.042) | 0.085 (0.004) | 0.100 ** (0.004) | 0.113 ** (0.008) | <0.001 |
NfL Tertiles | 1st | 2nd | 3rd | ||
---|---|---|---|---|---|
MCI patients per NfL tertiles | n = 117 | n = 116 | n = 117 | p | p$ |
Age (years) | 74.2 (6.1) | 76.7 (6) | 79.3 (6.2) | <0.0001 | <0.0001 |
Women (%) | 53.0 (62) | 62.9 (73) | 62.4 (73) | 0.22 | 0.55 |
BMI (kg/m2) | 25.7 (4.1) | 24.8 (3.7) | 24.1 (3.9) | 0.0019 | 0.0003 |
MMSE at baseline (/30) | 25.3 (3.3) | 25.1 (3.7) | 23.5 (4) | 0.0003 | <0.0001 |
MMSE variation over 3yrs | −0.9 (1.62) | −1 (2.47) | −1.96 (2.61) | 0.0005 | 0.0012 |
1 or 2 APOE4 alleles (%) | 45,3 (53) | 44,8 (52) | 40,2 (47) | 0.74 | 0.82 |
Hippocampal volume (R 1 L) (cm3) | 4.4 (1.25) | 4.45 (1.12) | 4.17 (1.34) | 0.19 | 0.71 |
Conversion at 3 years follow up (%) | 22.1 (15) | 23.1 (15) | 30.4 (17) | 0.52 | 0.99 |
Blood biomarkers | |||||
Creatinine (μmol/L) | 73 (13.1) | 76.8 (17.7) | 86 (30.7) | <0.0001 | <0.0001 |
eGFR (mL/min/1.73 m2) | 83.1 (11.6) | 77.9 (14.4) | 70.8 (17.2) | <0.0001 | <0.0001 |
Plasma Aβ1-40 (ng/L) | 250.7 (51.8) | 272.4 (56.3) | 287.1 (74.3) | <0.0001 | 0.0058 |
Plasma Aβ1-42 (ng/L) | 35.6 (10.4) | 38 (11.7) | 40 (12) | 0.0046 | 0.21 |
Plasma Aβ1-42/Aβ1-40 ratio | 0.145 (0.041) | 0.142 (0.041) | 0.142 (0.036) | 0.61 | 0.39 |
Plasma NfL (ng/L) | 11.6 (2.4) | 17.8 (2.2) | 34.2 (24.8) | <0.0001 | <0.0001 |
MMSE Decline/Year | t-Test | ||||||
---|---|---|---|---|---|---|---|
Tertiles | 1 | 2 | 3 | 1 vs. 2 | 1 vs. 3 | 2 vs. 3 | |
Plasma NfL | Mean | −0.92 | −0.973 | −1.991 | 0.8518 | 0.0003 | 0.0030 |
SD | 1.6291 | 2.4495 | 2.6228 | ||||
Plasma Aβ1-42/Aβ1-40 ratio | Mean | −1.144 | −1.593 | −1.093 | 0.1587 | 0.8664 | 0.1115 |
SD | 2.2044 | 2.3968 | 2.1411 |
All MCI | MCI NConv | MCI Conv | |||
---|---|---|---|---|---|
Demographic characteristics | n = 189 | n = 142 | n = 47 | p | p$ |
Age (years) | 77.5 (5.2) | 76.9 (4.9) | 79.3 (5.5) | 0.007 | NA |
Women (%) | 59.3 (112) | 59.1 (84) | 59.6 (28) | 0.96 | NA |
BMI (kg/m2) | 24.6 (3.5) | 24.6 (3.5) | 24.7 (3.5) | 0.91 | 0.69 |
1 or 2 APOE4* alleles | 60.8 (115) | 31.7 (45) | 61.7 (29) | 0.0002 | NA |
Cognitive biomarkers | |||||
MMSE (/30) | 26.6 (2.6) | 27.1 (2.4) | 25 (2.7) | <0.0001 | <0.0001 |
Brain morphological biomarkers | |||||
Hippocampal volume (R 1 L) (cm3) | 4.72 (1.1) | 4.92 (1.01) | 4.08 (1.15) | <0.0001 | <0.0001 |
Blood biomarkers | |||||
eGFR (mL/min/1.73 m2) | 77.6 (14.9) | 76.8 (15.7) | 79.6 (12.2) | 0.28 | 0.068 |
Plasma Aβ1-40 (ng/L) | 278.2 (58) | 276.8 (52.7) | 283.3 (74.7) | 0.54 | 0.80 |
Plasma Aβ1-42 (ng/L) | 38.9 (11.6) | 39.8 (11.3) | 35.7 (12.1) | 0.05 | 0.04 |
Plasma Aβ1-42/Aβ1-40 ratio | 0.142 (0.039) | 0.146 (0.039) | 0.127 (0.032) | 0.008 | 0.011 |
Plasma NfL (ng/L) | 19.8 (10.9) | 20 (11.8) | 19.2 (7.4) | 0.66 | 0.36 |
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Lehmann, S.; Schraen-Maschke, S.; Vidal, J.-S.; Blanc, F.; Paquet, C.; Allinquant, B.; Bombois, S.; Gabelle, A.; Delaby, C.; Hanon, O., on behalf of the BALTAZAR Study Group. Blood Neurofilament Levels Predict Cognitive Decline across the Alzheimer’s Disease Continuum. Int. J. Mol. Sci. 2023, 24, 17361. https://doi.org/10.3390/ijms242417361
Lehmann S, Schraen-Maschke S, Vidal J-S, Blanc F, Paquet C, Allinquant B, Bombois S, Gabelle A, Delaby C, Hanon O on behalf of the BALTAZAR Study Group. Blood Neurofilament Levels Predict Cognitive Decline across the Alzheimer’s Disease Continuum. International Journal of Molecular Sciences. 2023; 24(24):17361. https://doi.org/10.3390/ijms242417361
Chicago/Turabian StyleLehmann, Sylvain, Susanna Schraen-Maschke, Jean-Sébastien Vidal, Frédéric Blanc, Claire Paquet, Bernadette Allinquant, Stéphanie Bombois, Audrey Gabelle, Constance Delaby, and Olivier Hanon on behalf of the BALTAZAR Study Group. 2023. "Blood Neurofilament Levels Predict Cognitive Decline across the Alzheimer’s Disease Continuum" International Journal of Molecular Sciences 24, no. 24: 17361. https://doi.org/10.3390/ijms242417361