Association Between Low Birth Weight and Dementia Risk: A Large-scale Prospective Study.

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 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. 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 ( 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.