Glycemic index, glycemic load, and risk of dementia: a prospective analysis within the UK Biobank cohort

Abstract Background Dementia risk is influenced by metabolic and lifestyle factors, including hyperinsulinemia, chronic inflammation, and type 2 diabetes. Glycemic index (GI) and glycemic load (GL) reflect the quality and quantity of dietary carbohydrates and their impact on glucose metabolism and systemic health. However, their associations with the risk of dementia subtypes remain unclear. This study examined the associations between dietary GI and GL and the risk of all-cause and different dementia subtypes, such as Alzheimer’s disease (AD), vascular dementia (VD), and frontotemporal dementia. Methods A prospective analysis was conducted by using data from 202 302 dementia-free participants in the UK Biobank cohort. Dietary GI and GL were estimated by using the Oxford WebQ 24-hour web-based dietary questionnaire. Cox proportional hazards regressions with restricted cubic splines were used to evaluate nonlinear relationships. Two-piece Cox models were used to identify inflection points, which served as reference values to estimate hazard ratios (HRs). Results Dementia incidence was 0.89 per 1000 person-years. GI (mean±SD: 48.71 ± 7.68) showed an inverse J-shaped association with dementia risk, while GL (121.49 ± 39.00) showed a J-shaped pattern, with inflection points at 49.30 and 111.01, respectively. After adjusting for potential confounders, GI values of <49.30 were inversely associated with dementia risk [HR, 0.838; 95% confidence interval (CI), 0.758–0.926], while GL values of >111.01 were associated with higher dementia risk (HR, 1.145; 95% CI, 1.048–1.251). Similar findings were observed for AD and VD. Conclusion Low-GI diets may offer protective effects against all-cause dementia, AD, and VD, whereas high-GL diets may increase the risk. These findings underscore the importance of considering both carbohydrate quality and quantity in dementia prevention and management strategies.