It is well known that the incidence of Alzheimer’s disease (AD) and other types of dementia have been on the rise, but a new report presented at the recent Alzheimer’s Association International Conference (AAIC) suggests that in the next three decades, the numbers may triple.¹ Researchers estimate that more than 150 million people may be living with dementia by the year 2050, up from around 50 million now, with the highest increases in prevalence occurring in some of the world’s poorest regions.¹ With the lack of available pharmaceuticals for prevention or treatment, other methods will become critical to preventing this rise in global burden. Research has consistently shown that diet and lifestyle are effective in preventing dementia onset. Now, a new study finds that eating at least half a serving per day of foods rich in flavonoids has a substantial impact on subjective cognitive decline (SCD), a frequent dementia precursor.²

Flavonoids and Cognitive Function

In the study, published in the journal Neurology, researchers prospectively examined associations between long-term dietary intake of flavonoids (flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, polymeric flavonoids, and proanthocyanidins) and SCD in 49,493 women from the Nurses’ Health Study and 27,842 men from the Health Professionals Follow-up Study. After adjusting for age, total energy intake, major nondietary factors, and specific dietary factors, a higher intake of total flavonoids was associated with lower likelihood of self-reported SCD during follow up. Individuals in the highest quintile (about 600 mg daily on average, or about half a serving of flavonoid-rich foods) of daily consumption had about a 20% lower risk of SCD relative to peers in the lowest quintile (about 150 mg daily; OR = 0.81).²

The strongest protective associations were found for flavones (OR = 0.62), flavanones (OR = 0.64), and anthocyanins (OR = 0.76). The dose-response curve was steepest for flavones, followed
by anthocyanins.²

SCD is defined as when self-perceived cognitive decline is present but objective cognitive impairments cannot be detected, which may occur prior to clinically apparent mild cognitive impairment and dementia.³

Although some smaller studies have suggested that flavonoids may play a role in cognitive function and preventing cognitive decline,^4,5 larger trials have had mixed results.^6-11 This larger study, while it is based on subjective self reporting, provides some of the best evidence yet for the beneficial role of flavonoids
in cognitive decline.

Potential Mechanisms

Why might flavonoids have this effect? These phytochemicals are antioxidants and are well-known to reduce inflammation and oxidative stress in the body. While the exact mechanism of early cognitive impairment may differ among individuals, the progression to dementia is likely to involve inflammation and oxidative changes. Indeed, some of the other research that came out of the AAIC included the following findings, which suggests that anti-inflammatory antioxidant interventions could help prevent dementia:

• Proinflammatory diet is associated with increased risk of all-cause dementia.¹²
• A major shift in various metabolites involved in energy metabolism occurs in the 10-year period before the diagnosis of AD, including low levels of branched-chain amino acids and omega-3 fatty acids and high levels of glucose, citrate, acetone, beta-hydroxybutyrate (BHB), and acetate.¹³
• Low-dose aspirin reduces risk of all-cause dementia, especially in subjects with coronary heart disease.¹⁴
• Certain plasma biomarkers of neuronal damage and neuroinflammation are markedly elevated in hospitalized COVID-19 patients with neurologic symptoms compared to hospitalized COVID-19 patients without such symptoms, suggesting that COVID-19 may accelerate AD symptoms and pathology.¹⁵
• Data from the English Longitudinal Study of Aging (ELSA) suggest that low to moderate levels of physical activity in later life significantly mitigate the increased risk for age-related dementia.¹⁶

Clearly, environmental and lifestyle factors play a major role in dementia pathogenesis and progression. To more clearly understand the specifics, the Alzheimer’s Association has launched a two-year clinical trial, called the US Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER), to examine the effects of lifestyle on cognitive health. Most functional medicine clinicians will already recognize the importance of environment and lifestyle in dementia, and while some lifestyle changes can be easier to implement than others, ensuring just half a serving per day of foods rich in flavonoids may be a sustainable way to reduce the impact of cognitive decline and dementia in your patients.

References

1. Nichols E, Vos T. The estimation of the global prevalence of dementia from 1990-2019 and forecasted prevalence through 2050: an analysis for the Global Burden of Disease (GBD) study 2019. Alzheimer’s Association International Conference (AAIC) 2021: Poster 51496. Presented July 27, 2021. https://alz.confex.com/alz/2021/meetingapp.cgi/Paper/51496
2. Yeh TS, Yuan C, Ascherio A, Rosner B, Willett W, Blacker D. Long-term dietary flavonoid intake and subjective cognitive decline in US men and women. Neurology. Published online July 28, 2021. doi:1212/WNL.0000000000012454
3. Rabin LA, Smart CM, Amariglio RE. Subjective cognitive decline in preclinical Alzheimer’s disease. Annu Rev Clin Psychol. 2017;13:369-396. doi:1146/annurev-clinpsy-032816-045136
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   maintain and improve cognitive function over a 6 h period in young healthy adults. Nutrients.
   2019;11(11):2685. doi:3390/nu11112685
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   Arch Neurol. 2010;67(7):819-825. doi:1001/archneurol.2010.144
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   risk of late-life incident dementia: the Honolulu-Asia Aging Study. Am J Epidemiol. 2004;159(10):959-967. doi:1093/aje/kwh124
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   of flavonoids and risk of dementia. Eur J Epidemiol. 2000;16(4):357-363. doi:1023/a:1007614613771
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11.  Devore EE, Kang JH, Breteler MM, Grodstein F. Dietary intakes of berries and flavonoids in
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12.  van Lent DM, Himali JJ, Gokingco H, et al. Higher Dietary Inflammatory Index scores are associated with increased incidence of all-cause dementia in the Framingham Heart Study. Alzheimer’s Association International Conference (AAIC) 2021: Poster 55364. Presented July 28, 2021. https://alz.confex.com/alz/2021/meetingapp.cgi/Paper/55364
13.  Van Duijn CM, Li J, Arnold M, et al. Profiling the metabolome of patients with dementia in the UK Biobank. Alzheimer’s Association International Conference (AAIC) 2021: Poster 56147. Presented July 26, 2021. https://alz.confex.com/alz/2021/meetingapp.cgi/Paper/56147
14.  Nguyen TNM, Schöttker B. Low-dose acetylsalicylic use shows protective association with Alzheimer’s disease incidence: results from two large prospective cohort studies. Alzheimer’s Association International Conference (AAIC) 2021: Poster 51297. Presented July 28, 2021. https://alz.confex.com/alz/2021/meetingapp.cgi/Paper/51297
15.  Wisniewski T, Boutajangout A, Frontera J, Debure L, Vedvyas A, Faustin A. Plasma biomarkers of neurodegeneration and neuroinflammation in hospitalized COVID-19 patients with and without new neurological symptoms. Alzheimer’s Association International Conference (AAIC) 2021: Poster 57892. Presented July 29, 2021. https://alz.confex.com/alz/2021/meetingapp.cgi/Paper/57892
16.  Feter N, Leite JS, Rombaldi A. Physical activity attenuates or even eliminates the risk of all-cause dementia associated with aging in older adults: a population-based cohort study. Alzheimer’s Association International Conference (AAIC) 2021: Poster 52890. Presented July 26, 2021. https://alz.confex.com/alz/2021/meetingapp.cgi/Paper/52890