Dietary flavonols and risk of Alzheimer's dementia

Authors: HOLLAND, THOMAS - Rush University Medical Center; AGARWAL, PUJA - Rush University Medical Center; WANG, YAMIN - Rush University Medical Center; LEURGANS, SUE - Rush University Medical Center; BENNETT, DAVID - Rush University Medical Center; BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MORRIS, MARTHA CLARE - Rush University Medical Center

Submitted to: Neurology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/14/2020
Publication Date: 1/19/2020
Citation: Holland, T.M., Agarwal, P., Wang, Y., Leurgans, S.E., Bennett, D.E., Booth, S.L., Morris, M. 2020. Dietary flavonols and risk of Alzheimer's dementia. Neurology. 94(16):e1749-1756. https://doi.org/10.1212/WNL.0000000000008981.
DOI: https://doi.org/10.1212/WNL.0000000000008981

Interpretive Summary: Flavonoids are a class of bioactive compounds in plants that have numerous functions including known antioxidant and anti-inflammatory properties and have been proposed as compounds of interest in dementia prevention. The flavonol subclass of flavonoids have high antioxidant and anti-inflammatory properties, yet few studies have examined their relations to risk of Alzheimer's dementia. The purpose of this study was to determine whether dietary intake of flavonols is associated with Alzheimer's dementia. The study was conducted among 921 participants of the Rush Memory and Aging Project, which is an ongoing study since 1997 in approximately 40 Chicago area retirement communities and public housing. Participants complete annual neurological evaluations, and since 2004, they also complete annual dietary assessments using a validated food frequency questionnaire. For this study, we excluded those without a baseline food frequency questionnaire, less than two neurological evaluations and those with a diagnosis of probable Alzheimer's dementia at baseline dietary assessment. Among the 921 participants, who were on average 81 years old and predominantly female, 220 developed Alzheimer's dementia. Participants with the highest intake of total flavonols had less incident Alzheimer's dementia when adjusted for common demographic and genetic factors known to increase risk for Alzheimer's dementia. Kaempferol, myricetin and isorhamnetin were individual flavols, the intake of which was associated with less Alzheimer's dementia. In contrast, the flavol quercetin was not associated with Alxzheimer's dementia. In summary, higher dietary intakes of flavonols may be associated with reduced risk of developing Alzheimer's dementia.

Technical Abstract: Importance: Flavonoids are a class of bioactive compounds in plants that have numerous functions including known antioxidant and anti-inflammatory properties, and have been proposed as compounds of interest in dementia prevention. The flavonol subclass is particularly potent in these properties yet few studies have examined their relations to risk of Alzheimer's dementia. Objective: To determine whether dietary intake of flavonols is associated with Alzheimer's dementia. Design: The study was conducted among participants of the Rush Memory and Aging Project an ongoing (1997-present) prospective cohort study. Participants completed annual neurological evaluations over a mean of 6.1 years (SD=3.3). Since 2004 annual dietary assessments using a validated food frequency questionnaire are also obtained on enrolled participants. Setting: Community-based cohort of older persons dwelling in approximately 40 Chicago area retirement communities and public housing. Participants: This study included 921 MAP participants. We excluded those without a baseline food frequency questionnaire, less than two neurological evaluations and those with a diagnosis of probable Alzheimer's dementia at baseline dietary assessment. Exposure: Dietary intake of flavonols, derived from the food frequency questionnaire. Main Outcomes: Incident Alzheimer's dementia by quintile of dietary intake of flavonols. Results: Among the 921 initially non-demented MAP participants in the analyzed sample, 220 developed Alzheimer's dementia. The mean age of the sample was 81.2 years (SD=7.2), with the majority (n=691, 75%) being female. Participants with the highest intake of total flavonols had higher levels of education and more participation in physical and cognitive activities. In Cox proportional hazard models, dietary intakes of flavonols was inversely associated with incident Alzheimer's dementia in models adjusted for age, sex, education, APOE-epsilon4, and participation in cognitive and physical activities. Hazard ratios for the fifth versus first quintiles of intake were 0.52, 95% confidence interval (CI): 0.33, 0.84 for total flavonol, 0.49 (95% CI: 0.31, 0.77) for kaempferol, 0.62 (95% CI: 0.4, 0.97) for myricetin, and 0.62 (95% CI: 0.39, 0.98) for isorhamnetin. Quercetin was not associated (HR = 0.69, 95% CI: 0.43, 1.09). Conclusion and Relevance: Higher dietary intakes of flavonols may be associated with reduced risk of developing Alzheimer's dementia.