Palmitoylethanolamide/Luteolin Supplementation in Older Adults Undergoing Cardiac Surgery

Postoperative Cognitive Dysfunction (POCD) is a common complication after surgery, particularly among older adults. It is characterized by cognitive impairment, reduced functional independence, and decreased quality of life. Growing evidence suggests that neuroinflammation plays a relevant role in POCD development and persistence. Palmitoylethanolamide (PEA) is an endogenous lipid mediator involved in the regulation of neuroinflammatory processes through the modulation of non-neuronal cells, while luteolin is a flavonoid with well-known antioxidant properties. Under conditions of prolonged neuroinflammation, endogenous PEA levels may be insufficient to adequately counteract pro-inflammatory signaling, making exogenous administration necessary. In this context, exogenous micronized and ultramicronized PEA (mPEA and umPEA) supplementation has been shown to modulate cognitive and executive functions, working memory, language, and activities of daily living. Moreover, the combination of umPEA and luteolin (PEALut) may produce synergistic effects by modulating neuroinflammation and supporting neuronal function. This study aims to evaluate whether postoperative administration of co-ultramicronized PEA and luteolin (700 mg + 70 mg in 10 mL), added to standard of care, may contribute to the mitigation of POCD in older adults undergoing elective cardiac surgery, compared to standard care alone.

Inclusion Criteria: * Age ≥ 65 years * Both genders * Undergoing elective aortic or mitral valve replacement/reconstruction with or without coronary artery bypass grafting (CABG), at the Cardiac Surgery Unit of IRCCS San Gerardo dei Tintori Foundation (Monza, Italy) * Prognosis quoad vitam ≥ 3 months * Availability of a formal or informal caregiver who can assist the participant in taking the prescribed dose and following the visit schedule * Any concomitant therapy should be stable * Written informed consent obtained prior to randomization (from the participant or caregiver if the participant is unable to sign but clearly expresses the will to participate) Exclusion Criteria: * Severe dementia diagnosis * Preoperative clinical diagnosis of delirium * Other treatments/medications that may improve cognition * Current treatment with m/umPEA or PEALut (Glialia®), or its use within 90 days prior to enrollment * Contraindications to the use of PEALut, including allergy to excipients contained in the supplement and previous adverse reactions to PEALut * Other clinical conditions or situations that could interfere with the study or prevent optimal participation, as judged by the researchers