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Association Between Low Birth Weight and Dementia Risk: A Large-scale Prospective Study
Xinyue Yu1,2,3, Qingping Xue1, Jingyi Li1,2
1Department of Epidemiology and Biostatistics, School of Public Health, Chengdu Medical College, Chengdu 610599, China.
Summary
Low birth weight increases dementia risk, including Alzheimer's disease and vascular dementia. Cardiometabolic diseases like diabetes and hypertension may mediate this link, with specific protein pathways identified.
Area of Science:
- Neuroscience
- Epidemiology
- Genomics
Background:
- Birth weight is a critical indicator of early-life development.
- Dementia risk is influenced by a complex interplay of genetic and environmental factors.
- Understanding early-life determinants of dementia is crucial for public health.
Purpose of the Study:
- To investigate the association between birth weight and dementia risk.
- To explore the mediating role of chronic diseases in this relationship.
- To identify biological pathways using large-scale proteomics.
Main Methods:
- Utilized UK Biobank data from 279,743 participants (aged 40-69).
- Categorized birth weight into low (≤2500g), normal (2500-3999g), and macrosomia (≥4000g).
- Employed multivariable Cox regression and proteomics analyses.
Main Results:
- Low birth weight was linked to increased risk for all-cause dementia (HR 1.18), Alzheimer's disease (HR 1.14), and vascular dementia (HR 1.22).
- A significant non-linear relationship was observed between birth weight and dementia risk.
- Cardiometabolic diseases (diabetes, stroke, hypertension, dyslipidemia) mediated 6.3%-15.8% of the low birth weight-dementia association.
- Proteomics identified 21 proteins enriched in viral protein interaction and cytokine signaling pathways.
Conclusions:
- Low birth weight is a significant risk factor for dementia.
- Cardiometabolic diseases in mid-adulthood may mediate the link between low birth weight and dementia.
- Specific protein pathways highlight biological mechanisms connecting low birth weight to dementia risk.
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