Study Finds Cognitive Decline Lowest in Those with Lots of Flavenols in Diet Interview with:

Thomas M Holland, MD, MSAssistant Professor Rush Institute for Health Aging Rush College of Medicine & Rush College of Health Sciences

Dr. Holland

Thomas M Holland, MD, MS
Assistant Professor
Rush Institute for Health Aging
Rush College of Medicine & Rush College of Health Sciences What is the background for this study?

Response: My late mentor Martha Clare Morris, ScD had published a manuscript investigating leafy green intake, and the nutrients found therein, and cognition. I wanted to take this thought a step further and investigate the potential association bioactives, found in vegetables, like leafy greens, has to cognition. Further, this is a continuation of the research I published in the green journal in 2020 associating flavonols to incident Alzheimer’s dementia. This study extends the understanding that flavonols are not only beneficial for the most detrimental outcome of Alzheimer’s dementia (in decreasing the risk), but also advantageous in mitigating components of the, clinical syndrome i.e. decreasing the rate of cognitive decline. What are the main findings?

green-leafy-vegetables-flavenolsResponse:  For total flavonols, the standardized units presented mean that if a person has the highest level of intake of flavonols vs the lowest, that is equivalent to a 32% reduction in the rate of cognitive decline.

In other words, in our study population those that consumed the highest level of flavonols (an average of 7 servings of dark leafy greens/week or one serving of dark leafy greens/day) versus the lowest had a 32% decrease in their rate of cognitive decline. What should readers take away from your report?

Response: The overarching take away I would want to state is It is never too early, or too late to start making healthy lifestyle changes, especially when it comes to diet. The research presented here adds to the ever-growing body of evidence that what we eat matters. A diet diverse in fruits and vegetables is critical for both cognitive and physical functioning. A robust, lifestyle is necessary for ones continued health and overall well-being, especially their brain health.

Eat your fruits and vegetables, particularly dark leafy greens, and drink some tea every now and again. A healthy diet that contains various fruits and vegetables is critical for continued health, especially brain health. It is generally known that the vitamins and minerals found in these food items are important. But, now we are understanding that it’s the entire composition of the food, inclusive of bioactives, like flavonols, that render these foods as beneficial. As our knowledge of cognitive decline and the disease process of Alzheimer’s dementia expands, and we recognize that it is multi-factorial we should prepare ourselves as best we can with multiple, scientifically based tools to help stave off the progression with an eye toward the ultimate goal of prevention.

I want to preface this with a statement. It is recognized that changing of any kind is difficult. Our relationship with food is unique in that we don’t inherently see food as good or bad although we do designate foods as healthy (good) and unhealthy (bad.) With that, there are modification we can make to better ourselves both physically and cognitively to work towards a long, healthy, and functional life. Goal-setting, resolve, and support are important for success.

Ideal foods to consume are dark leafy greens and other vegetables, nuts, berries, beans, whole grains, fish, poultry, and extra virgin olive oil or equivalent oil. What recommendations do you have for future research as a results of this study?

olive-oil-flavenols-nutritionResponse: In the flavonoid realm specifically, we initially want to confirm these findings through other prospective cohort studies, specifically a more diverse population wherein we can generalize our findings to the public at large. Thereafter, a clinical trial in which we could establish effect would be quite valuable and informative. Also, although we believe that the beneficial association we found is due to the antioxidant and anti-inflammatory properties of flavonols, it is imperative to elucidate through what specific biologic mechanisms flavonols are working in our bodies.  Further, determining how flavonols are metabolized once taken in through the diet, traverse the blood stream, and cross the blood brain barrier to actually function in the brain is necessary to accurately assess the need of foods in our diet that contain these bioactives. What is the mechanism of how these dietary flavonols are potentially impacting brain health:

Response: Through various biochemical reactions, free radicals and reactive oxygen species can cause cellular, and eventually, organ level damage. We call this damage to the cells in our bodies, oxidative stress. When we ingest foods that contain antioxidants like flavonols or vitamin E, those antioxidants act as reducing agents and essentially “destroy” those free radicals and prevent further cellular damage.

Flavonols also have anti-inflammatory properties. Although inflammation is a natural process in our bodies, necessary for multiple immune responses, sustained or over-activation of our immune system can cause damage. Dietary intake of foods that contain nutrients and bioactives with anti-inflammatory properties can potentially prevent the over-activation or continued response of inflammatory cells and thus avoid cellular damage.

The authors report no disclosures pertaining to this work.


Thomas Monroe Holland, Puja Agarwal, Yamin Wang, Klodian Dhana, Sue E. Leurgans, Kyla Shea, Sarah L Booth, Kumar Rajan, Julie A. Schneider, Lisa L. Barnes. Association of Dietary Intake of Flavonols With Changes in Global Cognition and Several Cognitive Abilities. Neurology, 2022; 10.1212/WNL.0000000000201541 DOI: 10.1212/WNL.0000000000201541

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Last Updated on November 26, 2022 by Marie Benz MD FAAD