Association of Sugar Restriction in Utero Through Age 2 Years on Dementia Risk Later in Life.

Abstract (English)

BACKGROUND AND OBJECTIVES: Excess sugar intake in early life may affect long-term brain health, but evidence for dementia is limited. We used the abrupt end of UK sugar rationing in September 1953 as a natural experiment to test whether exposure to sugar rationing during different windows within the first 1,000 days from conception was associated with adult risk of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD). METHODS: We analyzed UK Biobank participants born around the end of UK sugar rationing. Exposure was classified as rationing in utero only, in utero plus the first year of life, in utero plus 1-2 years of life, or no exposure. Incident dementia was identified from linked ICD-10 records. MRI of the brain and cognitive function were assessed in the imaging subcohort. Adjusted Cox and Gompertz models estimated HRs and 95% CIs, Fine-Gray models accounted for competing risk, and mediation analyses evaluated type 2 diabetes and hypertension. RESULTS: Among 64,737 participants included in the analysis, the mean age at recruitment was 54.6 years, and 56.4% were women; 40,963 were exposed to sugar rationing during fetal and/or early-childhood life, and 23,774 were unexposed. Compared with unexposed individuals, sugar rationing in utero plus the first year of life was associated with lower hazards of all-cause dementia (HR, 0.79; 95% CI 0.66-0.94) and AD (HR, 0.77; 95% CI 0.59-1.00). Similar or slightly stronger associations were observed for exposure in utero plus 1-2 years (all-cause dementia: HR, 0.77; 95% CI 0.63-0.95; AD: HR, 0.72; 95% CI 0.53-0.98). Exposure in utero plus 1-2 years was associated with delayed onset of all-cause dementia by 2.55 years, AD by 2.87 years, and VaD by 2.49 years. Early-life sugar rationing was also associated with higher total gray matter volume (β, 3.27; 95% CI 0.46-6.07), lower white matter hyperintensity volume (β, -0.64; 95% CI -0.97 to -0.31), and better performance in processing speed and reasoning. Incident type 2 diabetes and hypertension jointly mediated 25.5% of the association. DISCUSSION: Sugar restriction in the first 1,000 days was associated with lower dementia hazards, delayed onset, and more favorable brain-health profiles. These results support early-life sugar reduction as a potential strategy for dementia prevention.