Sugary beverages and genetic risk in relation to brain structure and incident dementia: a prospective cohort study

Background: The relation of intake of sugary beverages and genetic predisposition to the long-term risk of dementia and brain structure remains unclear. Objectives: This study aimed to assess the associations of sugar-sweetened beverages (SSBs), artificially-sweetened beverages (ASBs), and natural juices (NJs) and the genetic predisposition with dementia risk and brain structure. Methods: We included 177,926 UK Biobank participants without dementia at baseline and followed them until March 2021. Intake of SSBs, ASBs, and NJs was assessed using repeated web-based 24-h dietary recalls from 2009 to 2012. We calculated a polygenic risk score (PRS) to indicate genetic predisposition of dementia for each individual. We estimated the HRs and 95% CIs using Cox proportional hazard models for dementia risk and β coefficients and 95% CIs using linear models for brain imaging markers. Results: During study follow-up (mean = 9.5 years), 1293 participants developed dementia (69.1 cases/100,000 person-years) excluding dementia cases within the first 2 years. Higher intake of SSBs and ASBs (>2 units/d compared with none) was each associated with a higher risk of dementia (HR: 1.34; 95% CI: 1.01, 1.77; P-trend = 0.040 for SSBs and 1.20; 95% CI: 0.84, 1.72; P-trend = 0.004 for ASBs). In contrast, moderate intake of NJs (>0–1 unit/d compared with none) was related to a lower dementia risk (HR: 0.77; 95% CI: 0.68, 0.87), a larger volume of brain gray matter (β = 0.05; 95% CI: 0.02, 0.08), and a lower volume of white matter hyperintensities (β = −0.07; 95% CI: −0.11, −0.03). The associations were not significantly modified by genetic risk (P-interactions = 0.839 for SSB × PRS, 0.732 for ASB × PRS, and 0.950 for NJ × PRS). Conclusions: Higher SSB and ASB intake was associated with higher risk of dementia, and moderate NJ intake was associated with a lower risk of dementia. Am J Clin Nutr 20XX;xx:xx–xx.