Volume 29, Issue 10 pp. 2913-2924
ORIGINAL ARTICLE

Circulating folate concentrations and the risk of mild cognitive impairment: A prospective study on the older Chinese population without folic acid fortification

Jingzhu Fu

Jingzhu Fu

Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China

Contribution: Data curation (lead), Formal analysis (lead), ​Investigation (equal), Methodology (lead), Writing - original draft (lead), Writing - review & editing (equal)

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Qian Liu

Qian Liu

Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China

Contribution: Formal analysis (supporting), ​Investigation (equal), Writing - original draft (supporting)

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Yun Zhu

Yun Zhu

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China

Department of Epidemiology & Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China

Contribution: Conceptualization (supporting), Formal analysis (supporting), Methodology (supporting), Writing - original draft (supporting), Writing - review & editing (equal)

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Changqing Sun

Changqing Sun

Neurosurgical Department of Baodi Clinical College of Tianjin Medical University, Tianjin, China

Contribution: ​Investigation (supporting)

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Huilian Duan

Huilian Duan

Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China

Contribution: ​Investigation (equal)

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Ling Huang

Ling Huang

Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China

Contribution: ​Investigation (equal)

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Dezheng Zhou

Dezheng Zhou

Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China

Contribution: ​Investigation (equal)

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Zehao Wang

Zehao Wang

Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China

Contribution: ​Investigation (equal)

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Jing Zhao

Jing Zhao

Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China

Contribution: ​Investigation (equal)

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Zhenshu Li

Zhenshu Li

Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China

Contribution: ​Investigation (equal)

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Fei Ma

Fei Ma

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China

Department of Epidemiology & Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China

Contribution: Conceptualization (supporting), Writing - review & editing (supporting)

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Wen Li

Wen Li

Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China

Contribution: Conceptualization (equal), Writing - review & editing (supporting)

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Huan Liu

Huan Liu

Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China

Contribution: Conceptualization (supporting), Writing - review & editing (supporting)

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Xumei Zhang

Xumei Zhang

Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China

Contribution: Conceptualization (supporting), Writing - review & editing (supporting)

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Yongjie Chen

Yongjie Chen

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China

Department of Epidemiology & Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China

Contribution: Conceptualization (supporting), Data curation (supporting), Writing - review & editing (supporting)

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Guangshun Wang

Guangshun Wang

Department of Tumor, Baodi Clinical College of Tianjin Medical University, Tianjin, China

Contribution: Conceptualization (supporting), Writing - review & editing (supporting)

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Yue Du

Corresponding Author

Yue Du

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China

Department of Social Medicine and Health Management, School of Public Health, Tianjin Medical University, Tianjin, China

Correspondence

Guowei Huang, Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, China.

Email: [email protected]

Yue Du, Department of Social Medicine and Health Management, School of Public Health, Tianjin Medical University, Tianjin, China.

Email: [email protected]

Contribution: Conceptualization (supporting), Writing - review & editing (supporting)

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Guowei Huang

Corresponding Author

Guowei Huang

Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China

Correspondence

Guowei Huang, Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, China.

Email: [email protected]

Yue Du, Department of Social Medicine and Health Management, School of Public Health, Tianjin Medical University, Tianjin, China.

Email: [email protected]

Contribution: Conceptualization (lead), Funding acquisition (lead), Project administration (lead), Supervision (lead)

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First published: 23 June 2022
Citations: 3

Jingzhu Fu, Qian Liu and Yun Zhu contributed equally to this work.

Funding information

This work was supported by grants from the National Natural Science Foundation of China (No. 81730091)

Abstract

Background

The longitudinal association between serum folate concentrations and the risk of cognitive impairment remains unclear in populations with low folate levels. We examined the association between serum folate concentrations and mild cognitive impairment (MCI) in older adults in China, where mandatory fortification of foods with folic acid has not been implemented. We further explored if homocysteine (Hcy) and leukocyte telomere length (LTL) mediate the association between serum folate and MCI.

Methods

We performed a longitudinal analysis of 3974 participants aged ≥60 years from the Tianjin Elderly Nutrition and Cognition (TENC) cohort study. The associations between serum folate level and the risk of cognitive impairment overall and stratified by apolipoprotein E (APOE) ε4 genotypes were evaluated using multivariable Cox proportional hazards models. The mediating effects of Hcy and LTL on the folate–MCI association were explored via a path analysis approach.

Results

Within a 3-year follow-up, we documented 560 incident MCI cases. After multivariable adjustment, higher serum folate concentrations were associated with lower incidence of MCI, with hazard ratios (95% confidence interval) across quartiles of folate (from lowest to highest concentrations) of 1.00 (reference), 0.66 (0.52, 0.83), 0.57 (0.45, 0.73), 0.66 (0.52, 0.84), respectively (p for trend <0.001). In mediation analyses, the status of serum folate deficiency and MCI were correlated via two intermediary pathways, Hcy and Hcy-telomere (p < 0.05).

Conclusions

Lower folate concentrations, independently of APOE genotype, were associated with increased risk of MCI among elderly Chinese people, a population with relatively low folate intake. Our data were compatible with the mediation hypothesis that the association between folate status and MCI was mediated by Hcy and LTL.

CONFLICT OF INTEREST

The authors have declared no conflicts of interest.

DATA AVAILABILITY STATEMENT

Data described in the manuscript, code book, and analytic code will be made available to editors upon request either before or after publication for checking. For data access, researchers can contact the corresponding authors (E-mail: [email protected]).

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