In our previous blogs we have touched upon a couple aspects of how diet can impact neurological function and risk for diseases like Alzheimer’s. As interdisciplinary studies are becoming increasingly more common, we are discovering even more ways that diet and exercise impact our overall health, genetics, and cognitive functioning. Today we will be focusing on a recent study suggesting that consumption of dietary flavonols, a class of molecules found in a variety of fruits and vegetables, might reduce risk for Alzheimer’s disease (AD) and improve cognitive functioning. In fact, if you read our blog regularly you may already know about one flavonoid (of which flavonols are a subclass), resveratrol, which is the predicted cause behind the “French Paradox”. If you aren’t familiar with the French Paradox you can read about it (and much more) on our blog at centerforcognitivehealth.com.
Flavonols (and flavonoids) are a subclass of molecules called polyphenols, given their name for the many phenol rings that make up their chemical structure. Because of this shape, they act as antioxidants and many have powerful anti-inflammatory properties. In animal studies flavonols improve memory and learning and decrease the severity of AD pathology including decreased deposition of beta-amyloid plaques and neurofibrillary tangles with reduced microgliosis. Recent research by the Rush Memory and Aging Project (MAP) has attempted to determine if these effects are generalizable to human models, focusing on four common flavonols: kaempferol, quercetin, myricetin, and isorhamnetin.
MAP began this study in 1997, taking a community of elderly volunteers with no known history of dementia, and began giving them yearly clinical neurological exams and comprehensive food frequency questionnaires (FFQ). They parsed apart the effect of diet on AD-induced dementia onset over the course of the next several years. As of 2018, 921 out of 1,920 participants were randomized in the study excluding individuals with possible AD diagnoses at screening and those with missing data. At each annual evaluation, the participants were given 19 cognitive tests later reviewed by a blinded neuropsychologist. A diagnostic classification for each individual was determined by a neurologist, geriatrician, and geriatric nurse practitioner. When analyzing these results, they took care to account for APOE genotyping, years of schooling, participation in cognitively stimulating activities, physical activity, depressive symptoms, and hypertension to control for any possible confounding variables causing cognitive dysfunction outside of dementia itself. Lastly, they analyzed the FFQ data based on the USDA’s Database for the Flavonoid Content of Selected Foods to determine each participant’s average flavonoid intake.
Among the 921 participants who did not have dementia at the beginning of the study, 220 developed AD dementia during the follow-up period (average follow-up period was 6.2 years), with a mean age of 81.2 years at onset. Statistical analysis of all this data determined that dietary intake of flavonols were significantly predictive of a 48% decreased risk for AD. In terms of the specific flavonols, isorhamnetin and myricetin were associated with a 38% decreased risk and kaempferol was associated with a 50% decreased risk. Quercetin showed no significant effect on AD risk. Considering that these flavonols frequently co-occur in fruits and vegetables, they also modeled them all simultaneously to determine if one or more of the statistically significant effects were simply due to presence of another flavonol. As it turned out, only kaempferol had an independent association with AD risk. In essence this means that the protective effects of the other flavonols discussed in this study were only present when they co-occurred with the presence of kaempferol, suggesting that kaempferol was the most (and possibly the only) effective biomodulator.
Kaempferol is abundant in leafy greens. As a general trend, it is clear that modifying one’s diet to include more fruits and vegetables of all kinds is likely to improve both general and cognitive health. However, with the rise of genomic testing, if you or someone you know becomes aware of an increased likelihood of AD it may be worth emphasizing intake of leafy greens and incorporating things like salad, broccoli, or peas into your culinary repertoire regularly. Additionally, while little research has been done on diet’s effect on symptomatic progression of those already suffering from AD, the antioxidant activity of flavonols like kaempferol may also be able to slow the disease progression. Hopefully, more research will be done on this particular topic in the future, but even if this is not the case, in this study those in the highest quintile of flavonol intake also had reduced risk of diabetes, hypertension, and stroke compared to the lowest quintile providing a serious possibility for increased quality of life overall.