Association Between Low Birth Weight and Dementia Risk:A Large-scale Prospective Study
- VernacularTitle:低出生体重与痴呆风险关联的大型前瞻性研究
- Author:
Xinyue YU
1
;
Qingping XUE
;
Jingyi LI
;
Peiqi ZHANG
;
Qingqing OUYANG
;
Xiaoxue LUO
;
Qian HE
;
Yongliu WANG
;
Ying ZHAO
;
Xiangwang HE
;
Fan LI
;
Yunhaonan YANG
;
Xiongfei PAN
Author Information
- Keywords: Birth weight; Dementia; Proteomics; Alzheimer's disease; Vascular dementia
- From: Journal of Sichuan University (Medical Sciences) 2025;56(3):697-710
- CountryChina
- Language:Chinese
- 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.Methods We used data from 279 743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2 500 g),normal birth weight(2 500-3 999 g),and macrosomia(≥4 000 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.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.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.
