Background: Fruits are an important source of flavonoids, and greater intake of dietary flavonoids in older adults has been shown to be associated with decreased risk of dementia. It is unclear whether this relationship is similar or different between younger adults and older adults., Objectives: We examined for associations between midlife and late-life intake of flavonoid-rich fruits and incident dementia. We hypothesized that greater total cumulative intake of flavonoid-rich fruits in midlife and late-life adults would be associated with reduced risk of all-cause dementia., Design: Longitudinal, cohort study design., Setting: Framingham Heart Study, which is a longitudinal, multi-generational community-based cohort based in Framingham, Massachusetts, USA., Participants: Participants from the Framingham Heart Study Offspring cohort were included (n = 2,790) who attended the fifth core exam between 1991 to 1995, and were dementia-free and at least 45 years of age at that time, as well as had valid food frequency questionnaires from the fifth to ninth core exams., Measurements: Consumption of fruits with high flavonoid content or are important contributors to overall flavonoid intake was collected via food frequency questionnaire. Flavonoid-rich fruits from the food frequency questionnaire included raisins or grapes, prunes, bananas, fresh apples or pears, apple juice or cider, oranges, orange juice, grapefruit, grapefruit juice, strawberries, blueberries, and peaches, apricots, or plums. Dementia ascertainment was based on a multidisciplinary consensus committee, and included all-cause dementia and Alzheimer's disease dementia diagnoses based on research criteria. Cox models were used to examine associations between cumulative fruit intake and incident dementia, stratified by midlife (45-59 years; n = 1,642) and late-life (60-82 years; n = 1,148)., Results: Greater cumulative total fruit intake in midlife, but not late-life, was significantly associated with a 44% decreased risk of all-cause dementia (HR = 0.56; 95% CI = 0.32 - 0.98; p = 0.044). Decreased risk of all-cause dementia was also associated with higher intake of apples or pears in midlife and late-life, as well as higher intake of raisins or grapes in midlife only, and higher intake of oranges, grapefruit, blueberries, and peaches, apricots, or plums in late-life only., Conclusions: Among participants from the Framingham Heart Study, greater overall consumption of flavonoid-rich fruits in midlife was associated with reduced risk of dementia, though intake of specific fruits in midlife and late-life may have a protective role against developing dementia. These findings may help to inform future recommendations on when dietary interventions may be most beneficial to healthy brain aging across the life course., Competing Interests: PMD has received research grants from the National Institute on Aging, DARPA, DOD, ONR, Salix, Avanir, Avid, Cure Alzheimer’s Fund, Karen L. Wrenn Trust, Steve Aoki Foundation, US Highbush Blueberry Council, and advisory fees from UMethod, Clearview, Lumos, Otsuka, Lundbeck, Compass, Sermo, Nutricia, and Transposon. PMD is a co-inventor of patents for the diagnosis or treatment of Alzheimer’s disease and a patent for infection detection. PMD owns shares in several biotechnology companies whose products are not discussed here. PMD serves on boards of health systems and advocacy groups. RA is a scientific advisor to Signant Health, and a consultant to Biogen and the Davos Alzheimer’s Collaborative (DAC). RA is also Director of the Global Cohort Development program for DAC. PHH has received research grants from the Alzheimer’s Association, National Institute on Aging, and US Highbush Blueberry Council. All other authors report no conflicts of interest.