Extra-Virgin Olive Oil Enhances the Blood–Brain Barrier Function in Mild Cognitive Impairment: A Randomized Controlled Trial
Abstract
:1. Introduction
2. Materials and Methods
2.1. Subjects and Study Design
2.2. Inclusion/Exclusion Criteria
2.3. Neuropsychological Evaluation
2.4. MRI Data Acquisition
2.5. N-Back Task
2.6. MRI Data Preprocessing
2.7. Task fMRI Activation Analysis
2.8. Resting-State fMRI Connectivity Analysis
2.9. Contrast-Enhanced MRI for BBB Permeability Analysis
2.10. Measurements of Plasma Aβ40, Aβ42, Tau and p-tau181, and Serum NFL Using SIMOA
2.11. Statistical Analysis
3. Results
3.1. Baseline Demographic and Clinical Characteristics
3.2. Effect of ROO and EVOO on Functional Connectivity and BBB Permeability
3.3. Functional Neuroimaging and N-Back Task
3.4. Effect of ROO and EVOO on Cognitive Measures
3.5. Effect of ROO and EVOO on Blood Biomarkers
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variable | ROO (n = 12) | EVOO (n = 13) | p Value |
---|---|---|---|
Male | 3 (25%) | 5 (38%) | |
Female | 9 (75%) | 8 (62%) | 0.47 |
Age (years) | 65.5 ± 4.4 | 67.5 ± 5.5 | 0.31 |
Bodyweight (kg) | 74.± 3 ± 12.4 | 85.1 ± 19.9 | 0.11 |
Education (years) | 15.8 ± 2.7 | 14.2 ± 3.7 | 0.25 |
MMSE | 27.83 ± 2.17 | 27.15 ± 2.64 | 0.49 |
CDR | 0.42 ± 0.19 | 0.38 ± 0.22 | 0.87 |
Functional Connection | Pair-Wise p-Values | ||||
---|---|---|---|---|---|
EVOO2 > EVOO1 | ROO2 vs. ROO1 | EVOO1 vs. ROO2 | EVOO1 vs. ROO1 | EVOO2 > ROO2 | |
L Precuneus ↔ L Parahippocampal Gyrus | 0.02 | 0.46 | 0.83 | 0.66 | 0.01 |
R Precuneus ↔ L Parahippocampal Gyrus | 0.02 | 0.41 | 0.78 | 0.50 | 0.05 |
L Postcentral Gyrus ↔ R Parahippocampal Gyrus | 0.03 | 0.93 | 0.80 | 0.77 | 0.04 |
L Postcentral Gyrus ↔ L Parahippocampal Gyrus | 0.05 | 0.76 | 0.98 | 0.80 | 0.04 |
R Postcentral Gyrus ↔ L Parahippocampal Gyrus | 0.05 | 0.31 | 0.50 | 0.91 | 0.01 |
L Lingual Gyrus ↔ L Parahippocampal Gyrus | 0.04 | 0.22 | 0.84 | 0.34 | 0.05 |
L Middle Frontal Gyrus ↔ L Parahippocampal Gyrus | 0.05 | 0.65 | 0.36 | 0.52 | 0.01 |
L Superior Parietal Lobule ↔ L Parahippocampal Gyrus | 0.04 | 0.06 | 0.52 | 0.35 | 0.01 |
BBB permeability | |||||
L Parahippocampal Gyrus | 0.00 | 0.60 | 0.69 | 0.27 | 0.00 |
R Parahippocampal Gyrus | 0.01 | 0.85 | 0.34 | 0.40 | 0.04 |
L Hippocampus | 0.03 | 0.87 | 0.15 | 0.21 | 0.05 |
R Hippocampus | 0.04 | 0.99 | 0.70 | 0.71 | 0.03 |
Variable | ROO (n = 12) | EVOO (n = 13) | ||
---|---|---|---|---|
Baseline (SD) | 6 Months (SD) | Baseline (SD) | 6 Months (SD) | |
Bodyweight (kg) | 74.3 (12.4) | 74.4 (13.1) | 85.1 (19.9) | 85.7 (21.3) |
MMSE | 27.83 (2.17) | 28.83 (1.47) | 27.15 (2.64) | 26.92 (2.78) |
CDR | 0.42 (0.19) | 0.13 (0.23) * | 0.38 (0.22) | 0.23 (0.26) * |
% with CDR 0.5 | 83% | 25% | 77% | 46% |
CDR-SOB | 2.1 (1.29) | 0.38 (0.53) *** | 1.88 (1.56) | 1.00 (1.14) *** |
WMS-IV Logical Memory | ||||
LM overall score | 16.3 (4.9) | 15.9 (4.4) | 12.5 (4.5) | 14.5 (5.3) * |
%Correct | ||||
LM I | 59.3 (18.9) | 56.3 (20.8) | 45.8 (19.6) | 52.4 (20.4) |
LM II | 55.2 (27.0) | 50.4 (17.7) | 31.5 (24.1) # | 44.9 (31.2) * |
LM II Recognition | 83.7 (12.3) | 88.1 (11.7) | 80.3 (16.2) | 82.5 (15.6) |
VR I | 37.9 (5.2) | 41.3 (3.5) * | 38.9 (6.5) | 41.2 (2.7) |
VR II | 41.3 (2.9) | 40.2 (4.6) | 42.8 (0.8) | 42.4 (2.2) |
VR II Recognition | 3.8 (1.2) | 3.8 (1.4) | 2.2 (1.5) # | 3.7 (1.6) * |
Blood biomarkers (pg/mL) | ||||
Aβ40 | 265 (40) | 256 (43) | 260 (86) | 259 (75) |
Aβ42 | 12.2 (2.0) | 11.1 (1.9) | 11.2 (3.1) | 10.3 (2.7) |
Aβ42/Aβ40 | 0.047 (0.004) | 0.044 (0.005) * | 0.044 (0.009) | 0.040 (0.007) ** |
Tau | 1.30 (0.42) | 1.40 (0.46) | 1.95 (0.91) # | 1.76 (0.74) |
p-Tau181 | 2.19 (0.70) | 1.85 (0.56) | 3.67 (2.94) | 2.97 (2.08) * |
p-Tau/t-Tau | 1.88 (0.95) | 1.53 (0.89) ** | 1.91 (1.03) | 1.62 (0.75) * |
NFL | 16.2 (4.5) | 16.8 (4.1) | 21.8 (9.3) | 23.0 (10.2) * |
ROO (n = 12) | EVOO (n = 13) | ||||
---|---|---|---|---|---|
Mean a (SD) | p | Mean a (SD) | p | 95% CI for Difference of Differences | |
MMSE | 1.00 (2.73) | 0.23 | −0.23 (1.54) | 0.60 | (−0.583, 3.044) |
CDR | −0.291 (0.257) | 0.0024 | −0.154 (0.240) | 0.039 | (−0.344, 0.068) |
WMS-IV | |||||
Overall score | −0.323 (5.068) | 0.83 | 2.034 (4.347) | 0.05 | (−5.897, 1.182) |
LM-I | −3.036 (20.9) | 0.63 | 6.615 (14.9) | 0.13 | (−24.573, 5.272) |
LM-II | −4.786 (29.17) | 0.58 | 13.451 (20.77) | 0.038 | (−39.056, 2.582) |
LM-IIR | 4.375 (9.80) | 0.15 | 2.244 (18.57) | 0.67 | (−10.321, 14.591) |
VR I | 3.333 (5.10) | 0.04 | 2.308 (4.35) | 0.08 | (−2.887, 4.938) |
VR II | −1.167 (4.43) | 0.38 | −0.385 (2.43) | 0.58 | (−3.706, 2.142) |
VR IIR | 0.0 (1.13) | 1.00 | 1.462 (1.81) | 0.013 | (−2.721, −0.202) |
ROO (n = 12) | EVOO (n = 13) | ||||
---|---|---|---|---|---|
Mean a (SD) | p | Mean a (SD) | p | 95% CI for Differences of Differences | |
Aβ40 | −8.835 (59.6) | 0.63 | −1.150 (56.8) | 0.94 | (−57.038, 41.669) |
Aβ42 | −1.29 (1.85) | 0.07 | −0.901 (2.15) | 0.158 | (−2.235, 1.456) |
Tau | 0.098 (0.42) | 0.46 | −0.180 (0.69) | 0.368 | (−0.220, 0.770) |
p-Tau 181 | −0.344 (0.66) | 0.12 | −0.698 (1.18) | 0.05 | (−0.476, 1.184) |
Aβ42/Aβ40 ratio | −0.0034 (0.004) | 0.041 | −0.0036 (0.004) | 0.007 | (−0.003, 0.004) |
p-Tau/Tau ratio | −0.347 (0.251) | 0.001 | −0.286 (0.446) | 0.039 | (−0.376, 0.253) |
NFL | 0.553 (2.25) | 0.43 | 1.206 (1.91) | 0.042 | (−2.414, 1.109) |
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Kaddoumi, A.; Denney, T.S., Jr.; Deshpande, G.; Robinson, J.L.; Beyers, R.J.; Redden, D.T.; Praticò, D.; Kyriakides, T.C.; Lu, B.; Kirby, A.N.; et al. Extra-Virgin Olive Oil Enhances the Blood–Brain Barrier Function in Mild Cognitive Impairment: A Randomized Controlled Trial. Nutrients 2022, 14, 5102. https://doi.org/10.3390/nu14235102
Kaddoumi A, Denney TS Jr., Deshpande G, Robinson JL, Beyers RJ, Redden DT, Praticò D, Kyriakides TC, Lu B, Kirby AN, et al. Extra-Virgin Olive Oil Enhances the Blood–Brain Barrier Function in Mild Cognitive Impairment: A Randomized Controlled Trial. Nutrients. 2022; 14(23):5102. https://doi.org/10.3390/nu14235102
Chicago/Turabian StyleKaddoumi, Amal, Thomas S. Denney, Jr., Gopikrishna Deshpande, Jennifer L. Robinson, Ronald J. Beyers, David T. Redden, Domenico Praticò, Tassos C. Kyriakides, Bonian Lu, Anna N. Kirby, and et al. 2022. "Extra-Virgin Olive Oil Enhances the Blood–Brain Barrier Function in Mild Cognitive Impairment: A Randomized Controlled Trial" Nutrients 14, no. 23: 5102. https://doi.org/10.3390/nu14235102