Olea europaea-derived interventions and cognitive outcomes across cognitive aging, mild cognitive impairment, and Alzheimer's disease: a systematic review of controlled clinical studies

Background Olive-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. Objective To 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. Methods PubMed, 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. Results Thirteen 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. Conclusions Olea 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.