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Peripheral immunity is associated with the risk of incident dementia

Molecular Psychiatry volume 27, pages 1956–1962 (2022)Cite this article

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Abstract

Central immunity components especially microglia in dementia have been well studied and corresponding immunotherapy gradually caught the attention. However, few studies focused on peripheral immunity and dementia. To address the issue, we examined the longitudinal association between incident dementia and peripheral immunity markers encompassing immune cell counts, and their derived ratios including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and lymphocyte-to-monocyte ratio (LMR), utilizing data of 361,653 participants from the UK Biobank (UKB). During a median follow-up of 8.99 years, 4239 participants developed dementia. The results revealed that increased innate immunity markers were associated with higher dementia risk (per SD increment hazard ratio [HR]; 95% confidence interval [CI] 1.14; 1.09–1.19 for neutrophils, 1.16; 1.11–1.20 for NLR and 1.11; 1.07–1.16 for SII), while increased adaptive immunity markers were associated with lower dementia risk (0.93; 0.90–0.97 for lymphocytes and 0.94; 0.90-0.98 for LMR). Our study pinpoints the differential role of innate and adaptive immunity in dementia incidence, which may provide some new perspectives in etiology and therapy of dementia.

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Fig. 1: Flowchart of the study.
Fig. 2: Survival analyses of dementia incidence involving the peripheral immune cells.
Fig. 3: Associations between peripheral immunity and incident dementia.

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Acknowledgements

This study utilized the UK Biobank Resource under application number 19542. We would like to thank all the participants and researchers from the UK Biobank. This study was supported by grants from the National Natural Science Foundation of China (91849126), Shanghai Municipal Science and Technology Major Project (No.2018SHZDZX01) 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.

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Authors and Affiliations

  1. Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China

    Ya-Ru Zhang, Shu-Fen Chen, Hui-Fu Wang, Shu-Yi Huang, Shi-Dong Chen, Qiang Dong & Jin-Tai Yu

  2. National Center for Neurological Disorders, Shanghai, China

    Ya-Ru Zhang, Shu-Fen Chen, Hui-Fu Wang, Shu-Yi Huang, Shi-Dong Chen, Qiang Dong & Jin-Tai Yu

  3. Department of Medical Biophysics and Biochemistry, Karolinska Institutet, Stockholm, Sweden

    Ji-Jing Wang

  4. The Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China

    Hui-Fu Wang, Yu-Zhu Li, Wei Cheng & Jian-Feng Feng

  5. Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China

    Hui-Fu Wang & Ya-Nan Ou

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  1. Ya-Ru Zhang
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Contributions

JTY conceptualized the study and revised the manuscript. YRZ, YZL, YNO, and WC analyzed and interpreted the data. SFC, HFW, and SYH prepared all the figures and tables. YRZ, JJW, and SDC drafted and revised the manuscript. JFF and QD critically revised the manuscript. All authors contributed to the writing and revisions of the paper and approved the final version.

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Correspondence to Jin-Tai Yu.

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Zhang, YR., Wang, JJ., Chen, SF. et al. Peripheral immunity is associated with the risk of incident dementia. Mol Psychiatry 27, 1956–1962 (2022). https://doi.org/10.1038/s41380-022-01446-5

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