Objective: To prospectively examine the associations between long-term dietary flavonoids and subjective cognitive decline (SCD).

Methods: We followed 49,493 women from the Nurses’ Health Study (NHS) (1984-2006) and 27,842 men from the Health Professionals Follow-up Study (HPFS) (1986-2002). Poisson regression was used to evaluate the associations between dietary flavonoids (flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, polymeric flavonoids, and proanthocyanidins) and subsequent SCD. For the NHS, long-term average dietary intake was calculated from seven repeated food frequency questionnaires (SFFQs), and SCD was assessed in 2012 and 2014. For the HPFS, average dietary intake was calculated from five repeated SFFQs, and SCD assessed in 2008 and 2012.

Results: Higher intake of total flavonoids was associated with lower odds of SCD after adjusting for age, total energy intake, major non-dietary factors, and specific dietary factors. Comparing the highest versus the lowest quintiles of total flavonoid intake, the pooled multivariable-adjusted odds ratios (ORs) (95% CIs) of 3-unit increments in SCD was 0.81 (0.76, 0.89). In the pooled results, the strongest associations were observed for flavones (OR=0.62 [0.57, 0.68]), flavanones (0.64 [0.58, 0.68)]), and anthocyanins (0.76 [0.72, 0.84]) (p trend <0.0001 for all groups). The dose-response curve was steepest for flavones, followed by anthocyanins. Many flavonoid-rich foods, such as strawberries, oranges, grapefruits, citrus juices, apples/pears, celery, peppers, and bananas, were significantly associated with lower odds of SCD.

Conclusion: Our findings support a benefit of higher flavonoid intakes for maintaining cognitive function in US men and women.