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Diet high in flavonols inversely associated with Alzheimer’s dementia

Natalia Reoutova
06 Feb 2020

A community-based prospective study of 921 older adults finds evidence that a diet high in flavonols, particularly kaempferol and isorhamnetin, may be protective against the development of Alzheimer’s dementia.

Participants of the Rush Memory and Aging Project (MAP) in the highest quintile of total flavonol intake had a 48 percent lower rate of developing Alzheimer’s dementia vs those in the lowest in the basic-adjusted model, which included the covariates of age, sex, education, APOE ɛ4, late-life cognitive activity, and physical activity (hazard ratio [HR], 0.52; 95 percent confidence interval [CI], 0.33 to 0.84; ptrend=0.006). [Neurology 2020;94:1-8] 

“We focused on flavonols because their biochemical composition likely makes them particularly effective antioxidants,” explained the researchers. [Biol Chem 2002;383:503-519; J Nat Prod 2000;63:1035-1042]

Among the flavonol constituents, isorhamnetin, kaempferol, and myricetin were each associated with a reduction in the rate of incident Alzheimer’s dementia, with reductions of 38 percent (HR, 0.62; 95 percent CI, 0.39 to 0.98; ptrend=0.02), 50 percent (HR, 0.50; 95 percent CI, 0.31 to 0.79; ptrend=0.002), and 38 percent (HR, 0.62; 95 percent CI, 0.40 to 0.97; ptrend=0.03), respectively, for persons in the fifth vs first quintiles of intake. “However, the findings for quercetin were not statistically significant,” noted the researchers.

The top food item contributors to isorhamnetin were pears, olive oil, wine, and tomato sauce; kale, beans, tea, spinach, and broccoli for kaempferol; tea, wine, kale, oranges, and tomatoes for myricetin; while tomatoes, kale, apples, and tea were the main sources of quercetin.

“In secondary analyses, we further adjusted for BMI and depression, covariates that may be both risk factors and clinical sequelae of Alzheimer’s dementia,” wrote the researchers. [Curr Alzheimer Res 2012;9:646-663] “The [protective] effect estimates for flavonols in these models were either materially unchanged or increased.” 

The researchers also explored potential effect modification in the observed associations by age (≤80 years, >80 years), sex, education (≤12 years, >12 years), and APOE ɛ4 status in the basic-adjusted model. “The only statistically significant modification of effect was by sex, such that the association of total flavonol intake was stronger in men (Q5 vs Q1: HR, 0.24; 95 percent CI, 0.08 to 0.76) than in women (Q5 vs Q1: HR, 0.59; 95 percent CI, 0.35 to 0.99),” they reported. 

“Animal studies have demonstrated that dietary flavonols improved memory and learning and decreased severity of Alzheimer disease neuropathology, including β-amyloid, tauopathy, and microgliosis. Furthermore, two previous human studies reported that high levels of flavonoid intakes are associated with lower risk of Alzhemier’s dementia,” wrote the researchers. [Food Chem 2012;135:2702-2707; Neuropharmacology 2015;93:134-145; JAMA2002;287:3223-3229; Eur J Epidemiol 2000;16:357-363] 

The current study represents the first in humans to specifically investigate the flavonol subclass, which is the most abundant dietary flavonoid.

While the study had a number of limitations, such as potential recall bias while completing a food frequency questionnaire, an almost exclusively white population, and the possible dietary changes in participants with subclinical Alzheimer’s dementia, its strengths, which included a prospective design, structured annual neurological and major lifestyle factor assessments, standardized diagnostic criteria for Alzheimer’s dementia, and a long follow-up period (up to 12 years) lend validity to the findings.

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