| Title: | Association Between Low Birth Weight and Dementia Risk: A Large-scale Prospective Study |
| Journal: | Journal of Sichuan University (Medical Sciences) |
| Published: | 20 May 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40964122/ |
| DOI: | https://doi.org/10.12182/20250560503 |
Publication 16449
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Abstract
Objective: To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases, and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.</p>
Methods: We used data from 279743 participants aged 40 to 69 years enrolled in the UK Biobank. Birth weight was categorized into low birth weight (≤ 2500 g), normal birth weight (2500-3999 g), and macrosomia (≥ 4000 g). Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes (Alzheimer's disease and vascular dementia). Proteomics analyses were conducted to identify proteins and the potential pathways involved.</p>
Results: Low birth weight was associated with higher risks for all-cause dementia and its subtypes. The hazard ratios were 1.18 (95% CI, 1.08-1.30) for all-cause dementia, 1.14 (95% CI, 1.00-1.31) for Alzheimer's disease, and 1.22 (95% CI, 1.01-1.48) for vascular dementia. A non-linear relationship was observed between birth weight and dementia risk (P for nonlinearity < 0.001). Certain cardiometabolic diseases in middle-aged adults, such as diabetes, stroke, hypertension, and dyslipidemia, played a significant mediating role in the relationship between low birth weight and dementia risk, with the mediation proportion being 6.3% to 15.8%. Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk, which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors, adipocytokine signaling, and cytokine-cytokine receptor interaction.</p>
Conclusion: Low birth weight is positively associated with dementia risk. Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk. A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.</p>
15 Keywords
- Adult
- Aged
- Alzheimer Disease
- Birth Weight
- Dementia
- Female
- Humans
- Infant, Low Birth Weight
- Infant, Newborn
- Male
- Middle Aged
- Proportional Hazards Models
- Prospective Studies
- Proteomics
- Risk Factors
13 Authors
- Xinyue Yu
- Qingping Xue
- Jingyi Li
- Peiqi Zhang
- Qingqing Ouyang
- Xiaoxue Luo
- Qian He
- Yongliu Wang
- Ying Zhao
- Xiangwang He
- Fan Li
- Yunhaonan Yang
- Xiongfei Pan
Enabling scientific discoveries that improve human health