Abstract
BackgroundThe dietary carbohydrate-to-fiber ratio (CFR) provides a comprehensive measure of carbohydrate quality; however, its association with cognitive outcomes remains unexplored. Given the distinct health effects of different types of carbohydrates, understanding the impact of CFR on dementia risk and brain structure is valuable.MethodsThis prospective cohort study analyzed 107,785 UK Biobank participants aged ≥ 55 years who completed at least one 24-hour dietary recall between 2011 and 2012, with follow-up until April 2024. CFR was calculated as the ratio of daily carbohydrate intake to fiber intake. Total carbohydrate and dietary fiber intake were included as secondary exposures. CFR outliers were excluded using Tukey’s method (3.0 × interquartile range). The primary outcome was all-cause dementia incidence identified through linked hospital and death registry data. Secondary outcomes were hippocampal volume, entorhinal cortical thickness and frontal cortical thickness. Cox proportional hazards models estimated dementia risk, and multiple linear regression analyzed MRI markers. Models were adjusted for age, sex, education, BMI, physical activity, smoking, alcohol intake, hypertension, diabetes, and total energy intake. Interactions between dietary factors and polygenic risk score (PRS) were examined.ResultsDuring a median follow-up of 11.8 years, 2,000 dementia cases occurred, corresponding to incidence rates of 1.44 and 1.82 per 1,000 person-years in the lowest and highest CFR quartiles, respectively. A higher CFR was significantly associated with increased dementia risk (HR per 1 SD = 1.07, 95% CI: 1.02-1.12, p = 0.003). The association was slightly attenuated in individuals with increased genetic susceptibility (p for interaction = 0.02). Total carbohydrate intake was associated with dementia risk (HR per 1 SD = 1.15, 95% CI: 1.05-1.25, p = 0.001), whereas fiber intake was not (p = 0.99). An elevated CFR was also associated with reduced entorhinal cortical thickness (FDR p = 0.03) and with thinner frontal pole, medial orbitofrontal cortex, and rostral middle frontal cortex (all FDR p = 0.01) among 14,388 participants with MRI data.ConclusionsA higher CFR was associated with increased dementia risk, reduced entorhinal thickness, and thinner frontal cortical regions, suggesting that CFR may serve as a practical indicator of carbohydrate quality with potential implications for dietary and public health approaches to cognitive aging.