Long-term Dietary Flavonoid Intake and Subjective Cognitive Decline in US Men and Women

Abstract

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 7 repeated semiquantitative food frequency questionnaires (SFFQs), and SCD was assessed in 2012 and 2014. For the HPFS, average dietary intake was calculated from 5 repeated SFFQs, and SCD was assessed in 2008 and 2012.

Results: Higher intake of total flavonoids was associated with lower odds of SCD after adjustment for age, total energy intake, major nondietary factors, and specific dietary factors. In a comparison of the highest vs the lowest quintiles of total flavonoid intake, the pooled multivariable-adjusted odds ratio (OR) of 3-unit increments in SCD was 0.81 (95% confidence interval [CI] 0.76, 0.89). In the pooled results, the strongest associations were observed for flavones (OR 0.62 [95% CI 0.57, 0.68]), flavanones (0.64 [0.58, 0.68)]), and anthocyanins (0.76 [0.72, 0.84]) (p trend <0.001 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.

Figure 1. Associations and Dose-Response Relationships Between Flavonoid Subclasses and SCD

(A and B) Multivariate odds ratios (ORs) for flavonoid subclasses by quintiles in the Nurses' Health Study (NHS) and Health Professionals Follow-Up Study (HPFS). (C and D) Multivariate-adjusted dose-response relationship between flavonoid subclasses and OR of 3-unit increments in subjective cognitive decline (SCD) in the NHS and HPFS.

Figure 2. Major Food Sources of Flavonoids By Subclass^a

^aAverage for 1984 to 2006 in the Nurses’ Health Study (NHS) and 1986 to 2002 in the Health Professionals Follow-Up Study (HPFS).

Figure 3. ORs^a (95% CIs) for Associations Between Food Sources of Flavonoids and 3-Unit Increments in SCD

Multivariate model: Nurses’ Health Study (NHS): adjusted for age, total energy intake, Census tract income, education (registered nursing degrees, bachelor degree, master or doctorate degree), husband's education (high school or lower education, college, graduate school), race (White, Black, other), smoking history (never, ≤4 pack-years, 5–24 pack-years, >24 pack-years), depression, physical activity level (metabolic equivalent-hours per week, quintiles), body mass index, intakes of alcohol, postmenopausal status and hormone replacement therapy use, family history of dementia, missing indicator for subjective cognitive decline (SCD) measurement at 2012 or 2014, number of dietary assessments during 1984 to 2006, multivitamin use (yes/no), and parity (nulliparous, 1–2, >2). Health Professionals Follow-Up Study (HPFS): adjusted for age, total energy intake, smoking history (never, ≤24 pack-years, 25–44 pack-years, ≥45 pack-years), cancer (yes/no), depression, family history of dementia, elevated physical activity level (metabolic equivalent-hours per week, quintiles), and body mass index, multivitamin use (yes/no), intake of alcohol, profession (dentist, pharmacist, optometrist, osteopath, podiatrist, veterinarian), missing indicator for SCD measurement at 2008 or 2012, and number of dietary assessments during 1986 to 2002. Both cohorts also adjusted for dietary intakes of sugar-sweetened beverages, sweets/desserts, whole grains, refined grains, and animal fat. The foods were ranked starting with the lowest odds ratios (ORs) based on the meta-results of the 2 cohorts. ^aORs for every 3 servings/wk as continuous variables. CI = confidence interval.

Figure 4. Temporal Relationships Between Flavone Intake and OR^a of 3-Unit Increments in SCD

Multivariate model: Nurses’ Health Study (NHS): adjusted for age, total energy intake, Census tract income, education (registered nursing degrees, bachelor degree, master or doctorate degree), husband's education (high school or lower education, college, graduate school), race (White, Black, other), smoking history (never, ≤4 pack-years, 5–24 pack-years, >24 pack-years), depression, physical activity level (metabolic equivalent-hours per week, quintiles), body mass index, family history of dementia, vitamin C, vitamin D, and vitamin E supplementation use (yes/no), intakes of alcohol, postmenopausal status and hormone replacement therapy use, missing indicator for subjective cognitive decline (SCD) measurement at 2012 or 2014, number of dietary assessments during 1984 to 2006, multivitamin use (yes/no), parity (nulliparous, 1–2, >2), and intakes of total carotenoids, vitamin C, vitamin D, vitamin E, and long-chain omega-3 fatty acid. Health Professionals Follow-Up Study (HPFS): adjusted for age, total energy intake, smoking history (never, ≤24 pack-years, 25–44 pack-years, ≥45 pack-years), cancer (yes/no), depression, physical activity level (metabolic equivalent-hours per week, quintiles), body mass index, multivitamin use (yes/no), intake of alcohol, family history of dementia, profession (dentist, pharmacist, optometrist, osteopath, podiatrist, veterinarian), percentage of energy intake from dietary total protein (quintiles), missing indicator for SCD measurement at 2008 or 2012, number of dietary assessments during 1986–2002, and intakes of total carotenoids, vitamin C, vitamin D, vitamin E, and long-chain omega-3 fatty acid. OR = odds ratio. ^aComparing 90th to 10th percentile of flavone intake.

Figure 5. Temporal Relationships Between Strawberry Intake and OR^a of 3-Unit Increments in SCD

Multivariate model: Nurses’ Health Study (NHS): adjusted for age, total energy intake, Census tract income, education (registered nursing degrees, bachelor degree, master or doctorate degree), husband's education (high school or lower education, college, graduate school), race (White, Black, other), smoking history (never, ≤4 pack-years, 5–24 pack-years, >24 pack-years), depression, physical activity level (metabolic equivalent-hours per week, quintiles), body mass index, family history of dementia, vitamin C, vitamin D, and vitamin E supplementation use (yes/no), intakes of alcohol, postmenopausal status and hormone replacement therapy use, missing indicator for subjective cognitive decline (SCD) measurement at 2012 or 2014, number of dietary assessments during 1984 to 2006, multivitamin use (yes/no), parity (nulliparous, 1–2, >2), and intakes of sugar-sweetened beverages, sweets/desserts, whole grains, refined grains, and animal fat. Health Professionals Follow-Up Study (HPFS): adjusted for age, total energy intake, smoking history (never, ≤24 pack-years, 25–44 pack-years, ≥45 pack-years), cancer (yes/no), depression, physical activity level (metabolic equivalent-hour per week, quintiles), and body mass index, multivitamin use (yes/no), intake of alcohol, family history of dementia, profession (dentist, pharmacist, optometrist, osteopath, podiatrist, veterinarian), percentage of energy intake from dietary total protein (quintiles), missing indicator for SCD measurement at 2008 or 2012, number of dietary assessments during 1986 to 2002, and intakes of sugar-sweetened beverages, sweets/desserts, whole grains, refined grains, and animal fat. OR = odds ratio. ^aOR for every 3 servings/wk as continuous variables.