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

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.

Keywords: Alzheimer’s disease; Birthweight; Cognitive function; Dementia; Vascular dementia.

Fig. 1

Flow chart of study design

Fig. 2

Effects of birthweight with dementia. A Plots show the hazard ratio for birthweight with the 3rd (Q3) as the reference level, adjusted for model 3. B Non-linearity of continuous birthweight with the risk of all causes of dementia. C The cumulative incidence for dementia assessment for the 1st (Q1) and 3rd (Q1) quartiles of birthweight. (Model 1: adjusted age and sex; model 2: adjusted age, sex, ethnicity, education, alcohol intake status, smoking status, Townsend deprivation index, mother history, father history, multiple birth, breastfed as a baby; model 3: adjusted age, sex, ethnicity, education, alcohol intake status, smoking status, Townsend deprivation index, mother history, father history, multiple birth, breastfed as a baby, physical activity, body mass index, coronary heart disease history, stroke history, diabetes history, hypertension history, HR hazard ratio, CI confidence interval)

Fig. 3

Associations between birthweight and brain structure. A Association of birthweight and volume of interest cortical regions. B Heatmap to overview the associations between birthweight and regional brain structure indices including area, thickness, and volumes. (Models were adjusted age, sex, ethnicity, education, alcohol intake status, smoking status, Townsend deprivation index, mother history, father history, multiple birth, breastfed as a baby, physical activity, body mass index, coronary heart disease history, stroke history, diabetes history, hypertension history; Bonferroni-corrected, *P < 0.05)