Dietary (Poly)phenol Intake, Inflammatory Biomarkers, and Mild Cognitive Impairment in Italian Adults

Dietary (poly)phenols have been proposed to protect against age-related cognitive decline through antioxidant, anti-inflammatory, and neuroprotective mechanisms. However, evidence specifically addressing mild cognitive impairment (MCI) remains limited. This study investigated the association between habitual dietary (poly)phenol intake, cognitive status, and circulating inflammatory biomarkers in older adults.

In this cross-sectional study, Italian adults aged ≥65 years attending a memory clinic underwent standardized neuropsychological assessment for MCI diagnosis. Habitual dietary intake was assessed using a validated food frequency questionnaire, and dietary (poly)phenol intake was estimated using the Phenol-Explorer database. Plasma transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) concentrations were measured by ELISA. Logistic regression analyses were performed to evaluate associations between quartiles of (poly)phenol intake and MCI after adjustment for energy intake, age, sex, education, and smoking status.

Participants without MCI reported significantly higher intakes of total (poly)phenols and several subclasses, including flavonoids, anthocyanins, flavanones, flavones, hydroxycinnamic acids, and lignans. Higher intakes of flavanones, flavones, lignans, hesperetin, naringenin, lariciresinol, matairesinol, and pinoresinol were positively associated with cognitive performance. Individuals in the highest quartile of total (poly)phenol intake had substantially lower odds of MCI (adjusted OR = 0.08; 95% CI: 0.01-0.62), with similar inverse associations observed for flavonoids (OR = 0.16; 95% CI: 0.02-0.92), lignans (OR = 0.18; 95% CI: 0.04-0.89), flavones (OR = 0.18; 95% CI: 0.04-0.87), naringenin (OR = 0.19; 95% CI: 0.04-0.92), lariciresinol (OR = 0.18; 95% CI: 0.04-0.89), matairesinol (OR = 0.19; 95% CI: 0.04-0.93), and pinoresinol (OR = 0.16; 95% CI: 0.03-0.82), when compared to the lowest quartile. Total (poly)phenol intake was not associated with circulating inflammatory biomarkers, although biochanin A and caffeic acid were inversely associated with TNF-α concentrations.

Higher habitual intake of selected dietary (poly)phenols, particularly flavonoids and lignans, was associated with a lower likelihood of MCI and better cognitive performance in older adults. However, the absence of consistent associations with inflammatory biomarkers does not support inference regarding an anti-inflammatory mechanism. Given the observational design, small sample size, and multiple statistical comparisons, these findings should be considered exploratory and hypothesis-generating. Prospective studies and randomized controlled trials are needed to confirm these associations and clarify the underlying biological pathways.