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Association of birthweight and risk of incident dementia: a prospective cohort study

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Abstract

Given the epidemiological studies investigating the relationship between birthweight and dementia are limited. Our study aimed to explore the association between birthweight and the risk of dementia, cognitive function, and brain structure. We included 275,648 participants from the UK Biobank, categorizing birthweight into quartiles (Q1 ≤ 2.95 kg; Q2 > 2.95 kg, ≤ 3.32 kg; Q3 > 3.32 kg, ≤ 3.66 kg; Q4 > 3.66 kg), with Q3 as the reference. Cox regression models and restricted cubic splines estimated the relationship between birthweight and the risk of all causes of dementia (ACD), Alzheimer’s disease (AD), and vascular dementia (VD). Multivariable linear regression models assessed the relationship between birthweight, cognitive function, and MRI biomarkers. Over a median follow-up of 13.0 years, 3103 incident dementia cases were recorded. In the fully adjusted model, compared to Q3 (> 3.32 kg, ≤ 3.66 kg), lower birthweight in Q1 (≤ 2.95 kg) was significantly associated with increased risk of ACD (HR = 1.18, 95%CI 1.06–1.30, P = 0.001) and VD (HR = 1.32, 95%CI 1.07–1.62, P = 0.010), but no significant association with AD was found. Continuous birthweight showed a U-shaped nonlinear association with dementia. Lower birthweight was associated with worse performance in cognitive tasks, including reaction time, fluid intelligence, numeric, and prospective memory. Additionally, certain brain structure indices were identified, including brain atrophy and reductions in area, thickness, and volume of regional subcortical areas. Our study emphasizes the association between lower birthweight and increased dementia risk, correlating cognitive function and MRI biomarkers of brain structure, suggesting that in utero or early-life exposures might impact cognitive health in adulthood.

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Data availability

The data that support the findings of this study are available from UK Biobank but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. All participants provided informed consent through electronic signature at baseline assessment.

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Funding

The project was supported by Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization (2021B1212040007), Clinical Frontier Technology Program of the First Affiliated Hospital of Jinan University, China (No. JNU1AF-CFTP-2022-a01235), and the Science and Technology Projects in Guangzhou, China (No. 202201020054, No. 2023A03J1032).

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Author notes

  1. Xiaxuan Huang, Shiqi Yuan, and Yitong Ling have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China

    Xiaxuan Huang, Shiqi Yuan, Yitong Ling, Shanyuan Tan & Anding Xu

  2. School of Nursing, Jinan University, Guangzhou, 510630, China

    Hongtao Cheng

  3. Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China

    Jun Lyu

  4. Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, 510630, China

    Jun Lyu

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Contributions

XH, SY, and YL guided the literature review and planned the analyses. HC and ST extracted the data from the UK database. JL and AX conceptualized the research aims. NH, SL, and LH participated in data analysis and interpretation. XH and SY wrote the first draft of the paper and the other authors provided comments and approved the final manuscript. JL and AX read and approved the final manuscript.

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Correspondence to Anding Xu or Jun Lyu.

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The UK Biobank study was approved by the Northwest Multi-centre Research Ethics Committee. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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The authors declare no competing interests.

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Huang, X., Yuan, S., Ling, Y. et al. Association of birthweight and risk of incident dementia: a prospective cohort study. GeroScience (2024). https://doi.org/10.1007/s11357-024-01105-3

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