Olea europaea-derived interventions and cognitive outcomes across cognitive aging, mild cognitive impairment, and Alzheimer's disease: a systematic review of controlled clinical studies
12 affiliations
- 1Department of Molecular Biology, Institute of Parasitology and Biomedicine “López-Neyra” (IPBLN-CSIC), Granada, Spain
- 2Unidad Docente Multiprofesional de Atención Familiar y Comunitaria, Reina Sofia University Hospital, Córdoba, Spain
- 3Microbiology and Parasitology Service, San Cecilio University Hospital, Granada, Spain
- 4Institute of Sustainable Agriculture, Spanish National Research Council, Córdoba, Spain
- 5Department of Endocrinology and Nutrition, San Cecilio University Hospital, Granada, Spain
- 6Biosanitary Research Institute of Granada (ibs.GRANADA), Granada, Spain
- 7Facultad de Ciencias de la Salud, Universidad Tecnológica Atlántico Mediterráneo—UTAMED, Málaga, Spain
- 8Department of Physiology, Faculty of Pharmacy, University of Granada, Granada, Spain
- 9Department of Nutrition and Food Sciences, Campus of Melilla, University of Granada, Melilla, Spain
- 100CIBER Physiopathology of Obesity and Nutrition (CIBERObn), Carlos III Health Institute, Madrid, Spain
- 111Department of Endocrinology and Nutrition, Virgen de las Nieves University Hospital, Granada, Spain
- 122Foundation for Biosanitary Research of Eastern Andalusia—Alejandro Otero (FIBAO), Granada, Spain
Abstract
BackgroundOlive-derived nutritional exposures range from phenolic-rich extra-virgin olive oil (EVOO) to refined oils, olive-leaf preparations, and isolated bioactives, but these matrices are frequently treated as interchangeable despite major compositional and physiological differences.ObjectiveTo systematically evaluate controlled human evidence relating oral Olea europaea-derived interventions to cognitive outcomes across cognitive aging, mild cognitive impairment (MCI), and Alzheimer's disease (AD), while distinguishing direct efficacy trials from broader dietary-pattern interventions and trials in which olive oil served as an active comparator.MethodsPubMed, Web of Science, and ClinicalTrials.gov were searched through 26 January 2026 and updated through 18 September 2026. Eligible reports contained a controlled human comparison involving an Olea-derived oral exposure or an olive-oil comparator and reported validated cognitive outcomes. Because the included studies represented different causal contrasts, intervention matrices, populations, instruments, and reporting structures, findings were synthesized narratively. Risk of bias and certainty of evidence were assessed using Cochrane RoB 2 and GRADE, respectively.ResultsThirteen reports representing 12 randomized intervention cohorts were included. Three reports directly tested an Olea-derived intervention, three evaluated EVOO within broader Mediterranean-diet interventions, and seven used olive oil primarily as the comparator for another bioactive intervention. Direct trials reported isolated, outcome-specific differences in ADAS-Cog, blood–brain barrier permeability, functional connectivity, and MMSE preservation, but these findings were inconsistent across global cognition, domain-specific measures, functional outcomes, and biological endpoints. Dietary-pattern findings could not isolate EVOO, whereas active-comparator trials estimated the effects of non-olive interventions relative to heterogeneous olive-oil controls. Three reports were judged at high risk of bias and the remaining ten raised some concerns; none was judged at low overall risk. Certainty was low to very low for most direct and dietary-pattern outcomes.ConclusionsOlea europaea-derived interventions should not be interpreted as a single therapeutic entity. Controlled evidence is sparse, heterogeneous, and predominantly of low or very low certainty. Selected studies report outcome-specific signals consistent with cognitive preservation or biological target engagement, but these findings do not establish clinical efficacy for the prevention or treatment of cognitive decline, MCI, or AD. Compositionally defined, adequately powered trials with prespecified clinically meaningful cognitive and functional outcomes are required before clinical recommendations can be made.
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BibTeX
@article{jimenezlozano2026olea,
title = {{Olea europaea-derived interventions and cognitive outcomes across cognitive aging, mild cognitive impairment, and Alzheimer's disease: a systematic review of controlled clinical studies}},
author = {Sandra Jiménez-Lozano and Diego Peña-Guzmán and Alberto Badillo-Carrasco and Daniel Pérez-Bartivas and María Teresa Zarco-Martín and María Teresa Zarco-Martín and María Teresa Zarco-Martín and Alfonso Varela-Lopez and Daniel Hinojosa-Nogueira and Daniel Hinojosa-Nogueira and Jose M. Romero-Márquez and Jose M. Romero-Márquez and Jose M. Romero-Márquez},
journal = {Frontiers in Nutrition},
year = {2026},
month = nov,
doi = {10.3389/fnut.2026.1981425},
url = {https://doi.org/10.3389/fnut.2026.1981425},
note = {CC BY},
}
RIS
TY - JOUR
TI - Olea europaea-derived interventions and cognitive outcomes across cognitive aging, mild cognitive impairment, and Alzheimer's disease: a systematic review of controlled clinical studies
AU - Sandra Jiménez-Lozano
AU - Diego Peña-Guzmán
AU - Alberto Badillo-Carrasco
AU - Daniel Pérez-Bartivas
AU - María Teresa Zarco-Martín
AU - María Teresa Zarco-Martín
AU - María Teresa Zarco-Martín
AU - Alfonso Varela-Lopez
AU - Daniel Hinojosa-Nogueira
AU - Daniel Hinojosa-Nogueira
AU - Jose M. Romero-Márquez
AU - Jose M. Romero-Márquez
AU - Jose M. Romero-Márquez
PY - 2026
DA - 2026/11/04
JO - Frontiers in Nutrition
DO - 10.3389/fnut.2026.1981425
UR - https://doi.org/10.3389/fnut.2026.1981425
AB - BackgroundOlive-derived nutritional exposures range from phenolic-rich extra-virgin olive oil (EVOO) to refined oils, olive-leaf preparations, and isolated bioactives, but these matrices are frequently treated as interchangeable despite major compositional and physiological differences.ObjectiveTo systematically evaluate controlled human evidence relating oral Olea europaea-derived interventions to cognitive outcomes across cognitive aging, mild cognitive impairment (MCI), and Alzheimer's disease (AD), while distinguishing direct efficacy trials from broader dietary-pattern interventions and trials in which olive oil served as an active comparator.MethodsPubMed, Web of Science, and ClinicalTrials.gov were searched through 26 January 2026 and updated through 18 September 2026. Eligible reports contained a controlled human comparison involving an Olea-derived oral exposure or an olive-oil comparator and reported validated cognitive outcomes. Because the included studies represented different causal contrasts, intervention matrices, populations, instruments, and reporting structures, findings were synthesized narratively. Risk of bias and certainty of evidence were assessed using Cochrane RoB 2 and GRADE, respectively.ResultsThirteen reports representing 12 randomized intervention cohorts were included. Three reports directly tested an Olea-derived intervention, three evaluated EVOO within broader Mediterranean-diet interventions, and seven used olive oil primarily as the comparator for another bioactive intervention. Direct trials reported isolated, outcome-specific differences in ADAS-Cog, blood–brain barrier permeability, functional connectivity, and MMSE preservation, but these findings were inconsistent across global cognition, domain-specific measures, functional outcomes, and biological endpoints. Dietary-pattern findings could not isolate EVOO, whereas active-comparator trials estimated the effects of non-olive interventions relative to heterogeneous olive-oil controls. Three reports were judged at high risk of bias and the remaining ten raised some concerns; none was judged at low overall risk. Certainty was low to very low for most direct and dietary-pattern outcomes.ConclusionsOlea europaea-derived interventions should not be interpreted as a single therapeutic entity. Controlled evidence is sparse, heterogeneous, and predominantly of low or very low certainty. Selected studies report outcome-specific signals consistent with cognitive preservation or biological target engagement, but these findings do not establish clinical efficacy for the prevention or treatment of cognitive decline, MCI, or AD. Compositionally defined, adequately powered trials with prespecified clinically meaningful cognitive and functional outcomes are required before clinical recommendations can be made.
SN - 2296-861X
ER -