A diet rich in flavonols is associated with slower cognitive decline

Flavonoids are polyphenolic compounds found in plants and in large quantities in fruits and vegetables in particular. These compounds are best known for their anti-inflammatory and antioxidant properties. Flavonoids have been associated in several previous studies with slowing age-related cognitive decline and dementia. However, few studies have attempted to identify which flavonoid subclasses and individual molecules are most active in protecting brain health. A recently published American study provides some answers by evaluating the effect of the intake of total flavonols and individual flavonols (kaempferol, quercetin, myricetin, isorhamnetin) on the cognitive performance of the elderly.

The study was conducted among 961 participants from the city of Chicago in the United States, aged 60 to 100, who were part of the Rush Memory and Aging Project cohort, and who were followed for 6.9 years on average. The participants, whose average age was 81 at the start of the study, were mostly female (75%), Caucasian (98%), and had an average of 15 years of schooling. Participants’ diet was assessed using a validated semi-quantitative questionnaire, and dietary flavonol intake was inferred from the collected data. The participants’ cognitive performance was assessed annually with a battery of 19 standardized tests.

A higher dietary intake of total flavonols and individual flavonols was associated with a lower rate of overall cognitive decline and several cognitive domains. A higher intake of total flavonols was associated with a slower decline in episodic memory (memories of personal events), semantic memory (memory of facts and concepts), perceptual speed, and working memory (short-term memory), but had no effect on visuospatial construction ability (understanding and representation of space in 2 and 3 dimensions).

Analysis of individual flavonols indicates that higher intakes of kaempferol and quercetin are associated with slower cognitive decline. In contrast, myricetin and isorhamnetin were not associated with an effect on global cognitive decline. Kale, beans, tea, spinach and broccoli were the foods highest in kaempferol among those consumed in this study. Tomatoes, kale, apples and tea were the foods highest in quercetin in this study.

The mechanisms underlying this favourable association are not yet well understood. The study authors suggest that the anti-inflammatory properties of flavonols may decrease the amplitude or duration of neuroinflammation. In addition, the antioxidant properties of flavonols could reduce or even prevent cell damage caused by oxidative stress, which generates reactive oxygen derivatives (free radicals, oxygenated ions, peroxides).

An earlier study by the same group of researchers reported that green leafy vegetables (spinach, kale, collard greens, lettuce) and certain constituents including kaempferol were associated with slowing overall cognitive decline. The authors concluded that “eating about one serving per day of green leafy vegetables and foods high in phylloquinone, lutein, nitrate, folate, α-tocopherol, and kaempferol may help slow cognitive decline with age.”

The protective role of certain flavonols on cognition has been demonstrated in animal models. Thus, quercetin supplementation improves memory and learning in transgenic mice used as an animal model of Alzheimer’s disease. In another study, kaempferol and myricetin improved memory and learning and reduced oxidative stress in mice used as a model of Alzheimer’s disease.

The prospective design of the American study does not make it possible to establish a causal link between dietary flavonol intake and cognition. Randomized clinical trials would confirm the role of flavonols on cognitive performance and, in the longer term, the prevention of cognitive decline associated with age. This type of study would also make it possible to clarify the dose-response relationship for optimal brain health. In any case, the study also has several strong points: a large number of participants, duration of the study, robust measurement of cognition by the 19 cognitive tests, validated questionnaires. The results were adjusted to minimize residual confounders, since it is possible that a higher dietary intake of flavonols is an indirect effect of a healthier diet. Among the limitations of this study are: self-reported food intake is subject to recall bias; because of their advanced age, participants are at risk of mild cognitive impairment that could cause errors when answering food questionnaires; there remains a possibility of reverse causation (cognitive decline may have altered participants’ eating habits). According to the authors, additional analyses (sensitivity analyses), however, indicate that reverse causation is unlikely.

The results of this study suggest that the consumption of fruits and vegetables (especially green leafy vegetables) in the elderly may not only help them maintain good health in general, but also delay or prevent cognitive decline. However, more studies are needed to confirm and better understand how flavonols slow cognitive and memory decline.