Sugary beverage intake and genetic risk of dementia in relation to incident dementia and brain structure: evidence from the UK Biobank

Abstract Importance: Sugary beverage intake was associated with higher risk of dementia, but the specific amounts and types related to it and its interactions with genetic predisposition to dementia remained poorly understood.Objective: To investigate the relation of sugary beverage intake and genetic preposition to the long-term risk of dementia and brain structure.Design, Setting, and Participants: We leveraged data of 187,994 UK Biobank participants without dementia at baseline and followed them until March 2021.Exposures: Intake of sugary beverages (SBs, one unit=250 ml), including sugar-sweetened beverages (SSB), artificially-sweetened beverages (ASB), and natural sweet juices (NSJ), was assessed using repeated web-based 24-h dietary recall from 2009 to 2012. A polygenic risk score (PRS) was calculated to capture each participant’s load of common genetic variants related to the risk of dementia.Main Outcomes and Measures: Incident dementia was identified through hospital admissions and death registries. Brain magnetic resonance imaging was conducted in a subgroup of 12,566 participants in 2014.Results: During a total of 1,790,996 person-years of follow up, 1,351 incident dementia cases were identified. Higher intake of SSB and ASB (>2 units/d v. none) was independently associated with a substantially increased risk of dementia (p-trend=0.013 for SSB, and <0.001 for ASB). The corresponding multivariable-adjusted hazard ratio [HR] and 95% confidence intervals [CI] were 1.47 (1.13~1.92), and 1.41 (1.00~1.99), respectively. The significant association of ASB was observed among ASB consumptions regardless of the intake level. In contrast, moderate intake of NSJ (0~1 unit/d v. none) was related to a decreased risk of dementia (HR=0.80, 0.71~0.90) and a larger volume of brain grey matter (beta=0.03, 0.01~0.06) and a lower volume of white matter hyperintensities (beta=-0.08, -0.13~-0.02). Moreover, the genetic risks were significantly magnified by higher intake of SSB and ASB, and was instead attenuated by moderate intake of NSJ (P-interaction<0.002).Conclusions and Relevance: Higher intake of SSB and ASB was associated with higher risk of dementia, especially among individuals at high genetic risk for dementia. Inversely, moderate NSJ intake was associated with a reduced risk of dementia, possibly through the beneficial role maintaining brain grey matter volume and reducing white matter hyperintensities.