Objectives: To investigate the association of total urinary polyphenols (TUP) and total dietary polyphenols (TDP) with cognitive decline in an older population. Design: The Invecchiare in Chianti (InCHIANTI) study, a cohort study with a 3-year of follow-up. Setting: tuscany, italy. Participants: Non-demented adults aged 65 and older (N=652). Measurements: TUP and TDP concentrations were analysed at baseline using the Folin-Ciocalteu assay and a validated food frequency questionnaire, respectively. Cognition was assessed using the Mini-Mental State Examination (MMSE) and Trail Making Test (TMT) at baseline and after three years of follow-up. A substantial cognitive decline was defined as a reduction in the MMSE score of 3 or more points and as an increase of at least 29 seconds on the TMT A and 68 seconds on the TMT B (these thresholds represent the worst 10% of the distribution of decline) or as test discontinued due to multiple mistakes in TMT A and B at follow-up. Results: Higher TUP levels were associated with lower risk of substantial cognitive decline on the MMSE (odds ratio [OR] comparing extreme tertiles = 0.53; 95% confidence interval [CI] = 0.34
0.85; P-trend = 0.008) and on the TMT-A (OR = 0.52; 95 % CI = 0.28
0.96; P-trend = 0.03), but not on TMT-B in a logistic regression model that adjusted for baseline cognitive score and potential confounding factors. TDP did not affect the developing substantial cognitive decline in both tests. Conclusion: High concentrations of polyphenols, a nutritional biomarker of polyphenol intake, were associated with a lower risk of substantial cognitive decline in the older population studied over a three-year period, suggesting a protective effect against cognitive impairment.