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Association of life course adiposity with risk of incident dementia: a prospective cohort study of 322,336 participants

Abstract

Cohort studies report inconsistent associations between body mass index (BMI) and all-cause incident dementia. Furthermore, evidence on fat distribution and body composition measures are scarce and few studies estimated the association between early life adiposity and dementia risk. Here, we included 322,336 participants from UK biobank to investigate the longitudinal association between life course adiposity and risk of all-cause incident dementia and to explore the underlying mechanisms driven by metabolites, inflammatory cells and brain structures. Among the 322,336 individuals (mean (SD) age, 62.24 (5.41) years; 53.9% women) in the study, during a median 8.74 years of follow-up, 5083 all-cause incident dementia events occurred. The risk of dementia was 22% higher with plumper childhood body size (p < 0.001). A strong U-shaped association was observed between adult BMI and dementia. More fat and less fat-free mass distribution on arms were associated with a higher risk of dementia. Interestingly, similar U-shaped associations were found between BMI and four metabolites (i.e., 3-hydroxybutrate, acetone, citrate and polyunsaturated fatty acids), four inflammatory cells (i.e., neutrophil, lymphocyte, monocyte and leukocyte) and abnormalities in brain structure that were also related to dementia. The findings that adiposity is associated with metabolites, inflammatory cells and abnormalities in brain structure that were related to dementia risk might provide clues to underlying biological mechanisms. Interventions to prevent dementia should begin early in life and include not only BMI control but fat distribution and body composition.

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Fig. 1: Associations between life course adiposity and all-cause incident dementia.
Fig. 2: Sex-specific estimated cutoffs in the adiposity-dementia association, and associations with dementia below and above cutoffs.
Fig. 3: The relationship between adiposity, metabolites, inflammatory cells and dementia.
Fig. 4: Associations between adiposity and brain structure.

Data availability

The data that support the findings of this study are available from 343 UK Biobank project site, subject to registration and application process. Further details can be found at https://www.ukbiobank.ac.uk.

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (82071201, 81971032), Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX01), Research Start-up Fund of Huashan Hospital (2022QD002), Excellence 2025 Talent Cultivation Program at Fudan University (3030277001), and ZHANGJIANG LAB, Tianqiao and Chrissy Chen Institute, and the State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education, Fudan University. WC was supported by grants from the National Natural Sciences Foundation of China (No. 82071997) and the Shanghai Rising-Star Program (No. 21QA1408700). The authors gratefully thank all the participants and professionals contributing to the UK Biobank.

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JTY generated the hypothesis and designed the study. JTY and WC had full access to all of the data in the study. JFF and WC were responsible for the cohort data. YTD performed the association analysis between life course adiposity and incident dementia. YZL and WC conducted the brain imaging analysis. YTD and YRZ performed the metabolite and inflammatory cell analyses. YTD, YZL, ADS, JS, and JTY wrote the first draft of the report and SYH, YNO, SDC, LY, JFF, WC, ADS, JS, WC, and JTY helped in revising the text. QD, JFF, WC, and JTY provide administrative, technical and material support. All authors read and approved the final manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

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Correspondence to Wei Cheng or Jin-Tai Yu.

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Deng, YT., Li, YZ., Huang, SY. et al. Association of life course adiposity with risk of incident dementia: a prospective cohort study of 322,336 participants. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01604-9

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