Science

Yu An, Limin Cao, Gang Zheng, Yashu Liu, Honghao Yang, Liangkai Chen, Yuhong Zhao, Xiaopeng Zhang, Yang Xia

Background: Sugar intake has been identified as a risk factor for incident dementia; however, the role of genetic susceptibility in such association remains unclear.

Methods: This cohort study involved 158,408 participants from the UK Biobank to explore the effect of genetic susceptibility on the association between dietary sugar intake and dementia risk. Data on sugar intake were evaluated using repeated web-based 24-hour dietary recalls. Polygenic risk scores (PRS) for sugar metabolism (Triglyceride Glucose, TyG), gut microbiota, and disease susceptibility (Alzheimer’s disease) were generated based on genome-wide association studies.

Results: Over a median follow-up period of 9.94 years, 1,219 dementia cases (0.7%) were documented. There were significant positive dose-response relationships between sugar intake and dementia risk (non-free sugar: HR, 95% CI, Quartile 4 vs. Quartile 1 = 1.26, 1.04–1.52; free sugar: 1.43, 1.20–1.70). Genetic susceptibility, including TyG-PRS, gut microbiota, and disease susceptibility, showed a combined effect on the association between sugar intake and dementia risk. Notably, significant interactions were observed between sugar intake, PRS for Ruminococcaceae UCG-014 and dementia, as well as between free sugar, PRS for Oscillospira and dementia. Participants with lower PRS of Ruminococcaceae UCG-014, or higher PRS of Oscillospira, posed a higher risk of dementia due to sugar intake.

Conclusion: Both free and non-free sugar intake are independent risk factors for dementia incidence. The role of genetic susceptibility among such association cannot be ignored. These results underscore the importance of personalized nutritional interventions targeting both dietary habits and genetic risk profiles in dementia prevention strategies.