Flavonoid-Rich Foods, Dementia Risk, and Interactions With Genetic Risk, Hypertension, and Depression

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Flavonoid-Rich Foods, Dementia Risk, and Interactions With Genetic Risk, Hypertension, and Depression

Amy Jennings, PhD¹; Alysha S. Thompson, MSci¹; Anna Tresserra-Rimbau, PhD^1,2,3; et al Joshua K. O’Neill, MSci¹; Claire Hill, PhD¹; Nicola P. Bondonno, PhD^1,4,5; Tilman Kühn, PhD^1,6,7; Aedín Cassidy, PhD¹

Author Affiliations Article Information

JAMA Netw Open. 2024;7(9):e2434136. doi:10.1001/jamanetworkopen.2024.34136

Key Points

Question  What is the association of a flavonoid-rich diet with dementia risk among UK adults?

Findings  In this cohort study of 121 986 UK Biobank participants, those with the highest adherence to a flavonoid-rich diet, specifically intakes of tea, red wine, and berries, had a lower risk of dementia. Reductions were more pronounced in participants with a high genetic risk, hypertension, and depressive symptoms.

Meaning  These findings suggest that increasing(Means nothing useful!) daily consumption of flavonoid-rich foods may lower dementia risk, especially in populations at high risk.

Abstract

Importance  A composite score of flavonoid-rich foods (flavodiet) may provide a clear public health message regarding the range of foods with the potential to lower dementia risk.

Objective  To examine associations of flavodiet score and intakes of flavonoid subclasses with dementia risk according to genetic risk and presence of depression and hypertension.

Design, Setting, and Participants  This prospective, population-based cohort study included dietary data from adults aged 40 to 70 years in the UK Biobank, recruited between 2006 and 2010, with a mean (SD) follow-up of 9.2 (1.5) years. The data analyses were conducted from September 1 to 30, 2023.

Exposure  Flavodiet score adherence and intake of flavonoid subclasses derived from 24-hour computerized dietary assessments.

Main Outcome and Measures  The main outcome was incident all-cause dementia and interactions with genetic risk, hypertension, and depressive symptoms using multivariable Cox proportional hazards regression models.

Results  The sample included 121 986 participants (mean [SD] age, 56.1 [7.8] years; 55.6% female; 882 with incident dementia). Comparing the highest with lowest quintile of flavodiet score, consuming 6 additional servings per day of flavonoid-rich foods was associated with a lower risk of dementia among all participants (adjusted hazard ratio [AHR], 0.72; 95% CI, 0.57-0.89), those at high genetic risk (AHR, 0.57; 95% CI, 0.42-0.78), and those with depressive symptoms (AHR, 0.52; 95% CI, 0.33-0.81) after multivariable adjustment. The greatest risk reduction was observed in participants consuming at least 2 of the following per day: 5 servings of tea, 1 serving of red wine, and 0.5 servings of berries, compared with those who did not achieve any of these intakes (AHR, 0.62; 95% CI, 0.46-0.84). Higher intakes of flavonoid subclasses, including anthocyanins, flavan-3-ols, flavonols, and flavones, of which tea, red wine, and berries are the main contributors, supported these findings, showing inverse associations with dementia risk.

Conclusions and Relevance  In this cohort study, high adherence to a flavonoid-rich diet score was associated with a lower risk of dementia, with reductions more pronounced in individuals with a high genetic risk, hypertension, and depressive symptoms. These findings suggest that simple dietary changes of increasing intakes of commonly consumed flavonoid-rich foods and drinks may lower dementia risk.

 Introduction

The worldwide prevalence of dementia continues to increase, with estimations of more than 50 million people living with dementia in 2020 and projections of 10 million new cases each year as population aging continues to accelerate.¹ Currently, there is no effective treatment for dementia, so preventive interventions to improve health and quality of life and reduce social and economic costs, currently estimated at £39.4 billion in the UK alone,² are a major public health priority.

While nonmodifiable risk factors, particularly age and genetics, contribute substantially to the development of dementia, evidence from cohort studies has shown that modifiable risk factors, such as diet, play an important role in prevention. Higher adherence to plant-based diets has been associated with a 21% lower risk of developing cognitive disorders and a 40% lower risk of Alzheimer disease,³ with diets rich in healthy plant-based foods showing the strongest associations with lower dementia risk.⁴ Flavonoids, a group of polyphenolic compounds found in plant-derived foods and beverages, such as fruits, vegetables, tea, red wine, and dark chocolate, have also been associated with a lower risk of dementia.^5,6 There is evidence that higher intakes of berries and tea specifically are associated with a lower risk of dementia and cognitive decline.^7-9 Mechanisms proposed for the neuroprotective influence of dietary flavonoids and their downstream metabolites include reducing neuroinflammation¹⁰; improving cerebrovascular blood flow, with many flavonoid metabolites able to permeate the blood-brain barrier and mediate the microbiome-gut-brain axis¹¹; and modulating major neuronal signal transduction pathways associated with synaptic plasticity.¹² Flavonoids have also been associated with risk factors for dementia, including hypertension and depression. Studies have reported inverse associations between flavonol, flavone, and flavanone intakes and depression risk.¹³ Furthermore, higher intakes of anthocyanins, polymers, and, specifically, the proanthocyanidin component of the flavan-3-ol polymer class have been associated with lower blood pressure.¹⁴

Identifying flavonoid-rich foods associated with improved health outcomes may aid in formulating dietary recommendations valuable for both intervention research and public health initiatives. As the major food sources of flavonoids are similar in different regions,^15,16 developing a composite score of flavonoid-rich foods may provide an opportunity to deliver a clear public health message on the range of foods with the potential to lower dementia risk.¹⁷

The aims of this study were therefore to investigate the associations between (1) our novel flavodiet score and (2) intakes of flavonoid subclasses and dementia risk. In addition, we examined these associations according to genetic risk for dementia and presence of depression and hypertension. We hypothesized that higher(Means nothing useful!) intakes of berries and tea and, subsequently, intakes of anthocyanins and flavan-3-ols would be associated with lower dementia risk.

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