{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:43:34Z","timestamp":1792035814735,"version":"4.4.0"},"reference-count":52,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Auburn University Presidential Awards for Interdisciplinary Research (PAIR)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Mild cognitive impairment (MCI) and early Alzheimer\u2019s disease (AD) are characterized by blood\u2013brain barrier (BBB) breakdown leading to abnormal BBB permeability ahead of brain atrophy or dementia. Previous findings in AD mouse models have reported the beneficial effect of extra-virgin olive oil (EVOO) against AD, which improved BBB and memory functions and reduced brain amyloid-\u03b2 (A\u03b2) and related pathology. This work aimed to translate these preclinical findings to humans in individuals with MCI. We examined the effect of daily consumption of refined olive oil (ROO) and EVOO for 6 months in MCI subjects on BBB permeability (assessed by contrast-enhanced MRI), and brain function (assessed using functional-MRI) as the primary outcomes. Cognitive function and AD blood biomarkers were also assessed as the secondary outcomes. Twenty-six participants with MCI were randomized with 25 participants completed the study. EVOO significantly improved clinical dementia rating (CDR) and behavioral scores. EVOO also reduced BBB permeability and enhanced functional connectivity. While ROO consumption did not alter BBB permeability or brain connectivity, it improved CDR scores and increased functional brain activation to a memory task in cortical regions involved in perception and cognition. Moreover, EVOO and ROO significantly reduced blood A\u03b242\/A\u03b240 and p-tau\/t-tau ratios, suggesting that both altered the processing and clearance of A\u03b2. In conclusion, EVOO and ROO improved CDR and behavioral scores; only EVOO enhanced brain connectivity and reduced BBB permeability, suggesting EVOO biophenols contributed to such an effect. This proof-of-concept study justifies further clinical trials to assess olive oil\u2019s protective effects against AD and its potential role in preventing MCI conversion to AD and related dementias.<\/jats:p>","DOI":"10.3390\/nu14235102","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T03:57:28Z","timestamp":1669867048000},"page":"5102","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Extra-Virgin Olive Oil Enhances the Blood\u2013Brain Barrier Function in Mild Cognitive Impairment: A Randomized Controlled Trial"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9792-7766","authenticated-orcid":false,"given":"Amal","family":"Kaddoumi","sequence":"first","affiliation":[{"name":"Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA"},{"name":"Center for Neuroscience, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Thomas S.","family":"Denney","sequence":"additional","affiliation":[{"name":"Center for Neuroscience, Auburn University, Auburn, AL 36849, USA"},{"name":"Auburn University MRI Research Center, Department of Electrical & Computer Engineering, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7471-5357","authenticated-orcid":false,"given":"Gopikrishna","family":"Deshpande","sequence":"additional","affiliation":[{"name":"Center for Neuroscience, Auburn University, Auburn, AL 36849, USA"},{"name":"Auburn University MRI Research Center, Department of Electrical & Computer Engineering, Auburn University, Auburn, AL 36849, USA"},{"name":"Department of Psychological Sciences, Auburn University, Auburn, AL 36849, USA"},{"name":"Alabama Advanced Imaging Consortium, Birmingham, AL 36849, USA"},{"name":"Key Laboratory for Learning and Cognition, School of Psychology, Capital Normal University, Beijing 100037, China"},{"name":"Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore 560030, India"},{"name":"Centre for Brain Research, Indian Institute of Science, Bangalore 560012, India"},{"name":"Department of Heritage Science and Technology, Indian Institute of Technology, Hyderabad 502285, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7389-3047","authenticated-orcid":false,"given":"Jennifer L.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Center for Neuroscience, Auburn University, Auburn, AL 36849, USA"},{"name":"Auburn University MRI Research Center, Department of Electrical & Computer Engineering, Auburn University, Auburn, AL 36849, USA"},{"name":"Department of Psychological Sciences, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J.","family":"Beyers","sequence":"additional","affiliation":[{"name":"Auburn University MRI Research Center, Department of Electrical & Computer Engineering, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Redden","sequence":"additional","affiliation":[{"name":"Biomedical Affairs and Research, Edward Via College of Osteopathic Medicine, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Pratic\u00f2","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Center at Temple, Lewis Katz School of Medicine Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tassos C.","family":"Kyriakides","sequence":"additional","affiliation":[{"name":"Yale School of Public Health, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonian","family":"Lu","sequence":"additional","affiliation":[{"name":"Auburn University MRI Research Center, Department of Electrical & Computer Engineering, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna N.","family":"Kirby","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology and Preventive Medicine and Public Health, Edward Via College of Osteopathic Medicine, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren T.","family":"Beck","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Via College of Osteopathic Medicine, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy D.","family":"Merner","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.tins.2005.02.001","article-title":"Neurovascular mechanisms of Alzheimer\u2019s neurodegeneration","volume":"28","author":"Zlokovic","year":"2005","journal-title":"Trends Neurosci."},{"key":"ref_2","first-page":"197","article-title":"Evidence of endothelial dysfunction in the development of Alzheimer\u2019s disease: Is Alzheimer\u2019s a vascular disorder?","volume":"3","author":"Kelleher","year":"2013","journal-title":"Am. 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