Long-term dietary flavonoid intake and risk of Alzheimer's disease and related dementias in the Framingham Offspring Cohort

Authors: SHISHTAR, ESRA - Tufts University; ROGERS, GAIL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BLUMBERG, JEFFREY - Tufts University; AU, RHODA - Boston University; JACQUES, PAUL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/25/2020
Publication Date: 4/22/2020
Citation: Shishtar, E.A., Rogers, G.T., Blumberg, J.B., Au, R., Jacques, P.F. 2020. Long-term dietary flavonoid intake and risk of Alzheimer's disease and related dementias in the Framingham Offspring Cohort. American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/nqaa079.
DOI: https://doi.org/10.1093/ajcn/nqaa079

Interpretive Summary: Dementia is regarded as one of the most significant public health challenges largely affecting adults over 65 years. Alzheimer's disease (AD) is the most common form of dementia, making up about 60-80% of its cases. Currently, 5.8 million Americans are living with AD and by 2050, that is projected to escalate to 14 million. Given the absence of effective drug treatments to treat dementia, extensive efforts are being made to identify modifiable risk factors that may lower the risk of developing dementia. Of the factors studied to date, diet high in fruits and vegetables presents significant promise. Such diets are rich in plant metabolites (phytonutrients) called flavonoids that have been linked to cognitive health in acute and short-term intervention studies but there are no well-designed long-term studies of flavonoids and risk of AD and other dementia. The aim of this study was to help fill this gap by assessing the long-term association between flavonoid intakes and risk of dementia and AD. Over an average follow-up of 19.6 years among 2809 participants, we observed that participants with the lowest intakes of total flavonoids and 4 types of flavonoids had significantly higher dementia and AD risks relative to those with moderate or high intakes. Our findings suggest that higher long-term intakes of flavonoids may have promising effects on dementia and AD risk.

Technical Abstract: Background: Prospective evidence on the protective effects of flavonoid intake on dementia and Alzheimer's disease (AD) risk is mixed, though previous observational studies are limited by misclassification of usual dietary flavonoid intake. Objective: To examine the prospective relationship between total and 6 classes of dietary flavonoid intake and risk of dementia/AD while addressing the limitations of earlier observational studies on this relationship. Design: We used data from the Framingham Heart Study Offspring Cohort at exams 5 through 9. Participants were free of dementia and had a valid food frequency questionnaire at baseline. Flavonoid intakes were updated at each exam to represent the cumulative average of intakes across the 5 exams, and were expressed as natural logarithms to handle their non-linear relationship with the outcomes dementia/AD. Cox proportional hazards regression was used to estimate the hazard ratios (HR) for the prospective association between the flavonoid intakes and incidence of dementia/AD, which demonstrates the relative risk for a proportional difference in intake. We used the ratio of the 75th to the 25th percentile of intake to determine the relative difference for each flavonoid class. Results: Mean baseline age was 59.2 years, and 52% of the participants were females. Over an average follow-up of 19.6 years among 2809 participants, there were 201 dementia events of which 165 were AD. After multivariate and dietary adjustments, total flavonoids and the 4 flavonoid classes, flavonols, flavan-3-ols, anthocyanins, and flavonoid polymers, were significantly inversely associated with dementia risk (flavonols, HR=0.69;P=0.001; flavan-3-ols, HR=0.76;P=0.007; anthocyanins, HR=0.63;P<0.001; flavonoid polymers, HR=0.68;P<0.001; total flavonoids, HR=0.77; P=0.01). The same pattern of associations was seen with AD. Conclusions: Our findings imply that higher long-term intakes of flavonoids may have promising effects on dementia and AD risk, with the greatest potential benefits for increased flavonoid intakes in individuals with lower levels of intake.