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July 28, 2021
Letter to the Editor

Long-term Dietary Flavonoid Intake and Subjective Cognitive Decline in US Men and Women

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Tian-Shin Yeh, MD, PhD https://orcid.org/0000-0002-2266-8920, Changzheng Yuan, ScD, Alberto Ascherio, MD, DrPH, Bernard A. Rosner, PhD, Walter C. Willett, MD, DrPH, and Deborah Blacker, MD, ScDAuthors Info & Affiliations
September 7, 2021 issue
97 (10) e1041-e1056
https://doi.org/10.1212/WNL.0000000000012454
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Abstract

Objective

To prospectively examine the associations between long-term dietary flavonoids and subjective cognitive decline (SCD).

Methods

We followed 49,493 women from the Nurses' Health Study (NHS) (1984–2006) and 27,842 men from the Health Professionals Follow-Up Study (HPFS) (1986–2002). Poisson regression was used to evaluate the associations between dietary flavonoids (flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, polymeric flavonoids, and proanthocyanidins) and subsequent SCD. For the NHS, long-term average dietary intake was calculated from 7 repeated semiquantitative food frequency questionnaires (SFFQs), and SCD was assessed in 2012 and 2014. For the HPFS, average dietary intake was calculated from 5 repeated SFFQs, and SCD was assessed in 2008 and 2012.

Results

Higher intake of total flavonoids was associated with lower odds of SCD after adjustment for age, total energy intake, major nondietary factors, and specific dietary factors. In a comparison of the highest vs the lowest quintiles of total flavonoid intake, the pooled multivariable-adjusted odds ratio (OR) of 3-unit increments in SCD was 0.81 (95% confidence interval [CI] 0.76, 0.89). In the pooled results, the strongest associations were observed for flavones (OR 0.62 [95% CI 0.57, 0.68]), flavanones (0.64 [0.58, 0.68)]), and anthocyanins (0.76 [0.72, 0.84]) (p trend <0.001 for all groups). The dose-response curve was steepest for flavones, followed by anthocyanins. Many flavonoid-rich foods such as strawberries, oranges, grapefruits, citrus juices, apples/pears, celery, peppers, and bananas, were significantly associated with lower odds of SCD.

Conclusion

Our findings support a benefit of higher flavonoid intakes for maintaining cognitive function in US men and women.

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Letters to the Editor
2 September 2021
Author Response: Long-term Dietary Flavonoid Intake and Subjective Cognitive Decline in US Men and Women
Tian-Shin Yeh, Postdoctoral Research Fellow | Harvard T.H. Chan School of Public Health
Changzheng Yuan, Research Professor | School of Public Health, Zhejiang University, Hangzhou, China
Alberto Ascherio, Professor of Epidemiology and Nutrition | Harvard T.H. Chan School of Public Health
Bernard A. Rosner, Professor in the Department of Biostatistics | Harvard T.H. Chan School of Public Health
Walter C. Willett, Professor of Epidemiology and Nutrition | Harvard T.H. Chan School of Public Health
Deborah Blacker, Professor in the Department of Epidemiology | Harvard T.H. Chan School of Public Health, MGH

We thank Dr. Abe for the response to our article.1 However, we noticed that the studies mentioned in the comment actually showed that higher intake of flavonoids was associated with lower risk of cardiovascular disease,2 cancers,3 stroke,4 and depression.5

Also, we are not recommending a specific intake of flavonoids, but rather suggesting daily intake of flavonoid-rich foods.

Disclosure

The authors report no relevant disclosures. Contact [email protected] for full disclosures.  

References

  1. 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 [published online ahead of print, 2021 Jul 28]. Neurology. 2021;10.1212/WNL.0000000000012454.
  2. Wang X, Ouyang YY, Liu J, Zhao G. Flavonoid intake and risk of CVD: a systematic review and meta-analysis of prospective cohort studies. Br J Nutr. 2014;111(1):1-11. doi:10.1017/S000711451300278X
  3. Chang H, Lei L, Zhou Y, Ye F, Zhao G. Dietary Flavonoids and the Risk of Colorectal Cancer: An Updated Meta-Analysis of Epidemiological Studies. Nutrients. 2018;10(7):950. Published 2018 Jul 23. doi:10.3390/nu10070950
  4. Gao Q, Dong JY, Cui R, et al. Consumption of flavonoid-rich fruits, flavonoids from fruits and stroke risk: a prospective cohort study [published online ahead of print, 2021 Jan 29]. Br J Nutr. 2021;1-8. doi:10.1017/S0007114521000404
  5. Chang SC, Cassidy A, Willett WC, Rimm EB, O'Reilly EJ, Okereke OI. Dietary flavonoid intake and risk of incident depression in midlife and older women. Am J Clin Nutr. 2016;104(3):704-714. doi:10.3945/ajcn.115.124545
22 August 2021
Reader Response: Long-term Dietary Flavonoid Intake and Subjective Cognitive Decline in US Men and Women
Kazuo Abe, Neurology | Hyogo College of Medicine Hospital

I was interested in the article by Yeh and others.1 A lot of studies have been published concerning the associations between diet and subjective cognitive decline (SCD). This study is based on a follow-up assessment spanning over 20 years, which is strongly persuasive. The authors conclude that many flavonoid-rich foods are significantly associated with lower odds of SCD. Their conclusion seems reasonable—however, previous studies suggest that higher flavonoid intake increases risk for cerebrovascular diseases or cancers.2,3 Other research reports that higher dietary flavonoid intake can be associated with decreased overall body composition in younger women.4 In older populations, dietary flavonoid intake may also increase risk of depression.5

Considering these merits and demerits of dietary flavonoid intake, appropriate intake should be suggested.

Disclosure

The author reports no relevant disclosures. Contact [email protected] for full disclosures.  

References

  1. 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 [published online ahead of print, 2021 Jul 28]. Neurology. 2021;10.1212/WNL.0000000000012454.
  2. Wang X, Ouyang YY, Liu J, Zhao G. Flavonoid intake and risk of CVD: a systematic review and meta-analysis of prospective cohort studies. Br J Nutr. 2014;111(1):1-11. doi:10.1017/S000711451300278X
  3. Chang H, Lei L, Zhou Y, Ye F, Zhao G. Dietary Flavonoids and the Risk of Colorectal Cancer: An Updated Meta-Analysis of Epidemiological Studies. Nutrients. 2018;10(7):950. Published 2018 Jul 23. doi:10.3390/nu10070950
  4. Gao Q, Dong JY, Cui R, et al. Consumption of flavonoid-rich fruits, flavonoids from fruits and stroke risk: a prospective cohort study [published online ahead of print, 2021 Jan 29]. Br J Nutr. 2021;1-8. doi:10.1017/S0007114521000404
  5. Chang SC, Cassidy A, Willett WC, Rimm EB, O'Reilly EJ, Okereke OI. Dietary flavonoid intake and risk of incident depression in midlife and older women. Am J Clin Nutr. 2016;104(3):704-714. doi:10.3945/ajcn.115.124545

Information & Authors

Information

Published In

Neurology®
Volume 97 • Number 10 • September 7, 2021
Pages: e1041-e1056
PubMed: 34321362

Copyright

© 2021 American Academy of Neurology.

Publication History

Received: February 7, 2021
Accepted: June 10, 2021
Published online: July 28, 2021
Published in print: September 7, 2021

Permissions

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Study Funding

This work was supported by grants from the NIH (UM1 CA186107, UM1 CA 167552).

Authors

Affiliations & Disclosures

Tian-Shin Yeh, MD, PhD https://orcid.org/0000-0002-2266-8920
From the Departments of Epidemiology (T.-S.Y., A.A., W.W., D.B.), Nutrition (T.-S.Y., A.A., W.W., C.Y.), and Biostatistics (B.R.), Harvard T.H. Chan School of Public Health, Harvard University; Channing Division of Network Medicine (T.-S.Y., A.A., W.W., C.Y., B.R.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; School of Public Health (C.Y.), Zhejiang University, Hangzhou, China; Department of Medicine (B.R.), Harvard Medical School; and Department of Psychiatry (D.B.), Massachusetts General Hospital, Harvard Medical School, Boston.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
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1.
NONE
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1.
NONE
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Changzheng Yuan, ScD
From the Departments of Epidemiology (T.-S.Y., A.A., W.W., D.B.), Nutrition (T.-S.Y., A.A., W.W., C.Y.), and Biostatistics (B.R.), Harvard T.H. Chan School of Public Health, Harvard University; Channing Division of Network Medicine (T.-S.Y., A.A., W.W., C.Y., B.R.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; School of Public Health (C.Y.), Zhejiang University, Hangzhou, China; Department of Medicine (B.R.), Harvard Medical School; and Department of Psychiatry (D.B.), Massachusetts General Hospital, Harvard Medical School, Boston.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
British Journal of Nutrition, statistical editor, 2017-2019
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
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Alberto Ascherio, MD, DrPH
From the Departments of Epidemiology (T.-S.Y., A.A., W.W., D.B.), Nutrition (T.-S.Y., A.A., W.W., C.Y.), and Biostatistics (B.R.), Harvard T.H. Chan School of Public Health, Harvard University; Channing Division of Network Medicine (T.-S.Y., A.A., W.W., C.Y., B.R.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; School of Public Health (C.Y.), Zhejiang University, Hangzhou, China; Department of Medicine (B.R.), Harvard Medical School; and Department of Psychiatry (D.B.), Massachusetts General Hospital, Harvard Medical School, Boston.
Disclosure
Scientific Advisory Boards:
1.
University of Rochester - Scientific Advisory Board of NIH-funded study
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NorthShore University HealthSystem, Evanston IL, 2019. Honorarium for talk on neurodegenerative diseases. University of Oslo, Norway. Honorarium as PhD defense opponent.
Editorial Boards:
1.
1) Journal of Parkinson Disease, Editorial board
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH R01 NS073633; 2011-2017; Role: PI DoD W81XWH-14-1-0131; 2014-2019; Role: PI NIH R01 NS045893; 2013-2018; Role: PI NIH 1U01NS-90259; 2015-2020; Role: PI of subcontract NIH R01 NS089619-01A1; 2015-2020; Role: PI NIH R01 NS097723; 2016-2021; Role: Co-Investigator NIH R01 NS103891; 2018-2023; Role: PI CDMRP MS170116; 2018-2021; Role: PI
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
ALS Association; 2019-2020; Role: PI
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
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1.
NONE
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1.
NONE
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Bernard A. Rosner, PhD
From the Departments of Epidemiology (T.-S.Y., A.A., W.W., D.B.), Nutrition (T.-S.Y., A.A., W.W., C.Y.), and Biostatistics (B.R.), Harvard T.H. Chan School of Public Health, Harvard University; Channing Division of Network Medicine (T.-S.Y., A.A., W.W., C.Y., B.R.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; School of Public Health (C.Y.), Zhejiang University, Hangzhou, China; Department of Medicine (B.R.), Harvard Medical School; and Department of Psychiatry (D.B.), Massachusetts General Hospital, Harvard Medical School, Boston.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Walter C. Willett, MD, DrPH
From the Departments of Epidemiology (T.-S.Y., A.A., W.W., D.B.), Nutrition (T.-S.Y., A.A., W.W., C.Y.), and Biostatistics (B.R.), Harvard T.H. Chan School of Public Health, Harvard University; Channing Division of Network Medicine (T.-S.Y., A.A., W.W., C.Y., B.R.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; School of Public Health (C.Y.), Zhejiang University, Hangzhou, China; Department of Medicine (B.R.), Harvard Medical School; and Department of Psychiatry (D.B.), Massachusetts General Hospital, Harvard Medical School, Boston.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
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1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
(1) Nutritional Epidemiology, Third Edition, textbook. Oxford University Press, 2013. received <$5000 over last 2 years (2) Eat, Drink, and Healthy: The Harvard Medical School Guide to Healthy Eating, second edition. Simon and Schuster, 2017. < $2,000
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Breast Cancer Research Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
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NONE
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Deborah Blacker, MD, ScD
From the Departments of Epidemiology (T.-S.Y., A.A., W.W., D.B.), Nutrition (T.-S.Y., A.A., W.W., C.Y.), and Biostatistics (B.R.), Harvard T.H. Chan School of Public Health, Harvard University; Channing Division of Network Medicine (T.-S.Y., A.A., W.W., C.Y., B.R.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; School of Public Health (C.Y.), Zhejiang University, Hangzhou, China; Department of Medicine (B.R.), Harvard Medical School; and Department of Psychiatry (D.B.), Massachusetts General Hospital, Harvard Medical School, Boston.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Experimental Gerontology, Member of Editorial Board, 2004-
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1)NINDS, U24 NS100591, 2016-present, co-I; (2) NIMH, T32MH017119, co-PI or co-PI 2006-present; (3) NIA, P30 AG062421, 2018-present, Core leader/co-leader; (4) NIA, P01 AG036694, 2010-present, Core leader; (5) NIA, U01 AG032984 2009-present, site PI; (6) NIA R01 AG058063 2016-present, co-I; (7) NIA R01 AG062282,2018-present, co-I; (8) NIA, R01AG063975 2019-present, co-I; (9) R01AG048351, 2015-19, co-I;(10) NIA, R01 MH091448-09S1, 2018-19, site PI; (11) NIA, 2P01AG032952, 2018-present, co-I; (12) NIA, U01AG045390, 2014-2019, co-I; (13) R01 AG062282, 2020-present, co-I
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author

Notes

Correspondence Dr. Willett [email protected]
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

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