Résumé
The pathophysiology of Alzheimeru2019s disease is complex and may include genetic, physiological, as well as nutritional factors, some of which may be linked through the life span. Sugars consumption has dramatically increased in western societies and is a public health issue. Studies in animal models suggest that excess sugars consumption increase u03b2-amyloid aggregation, tau phosphorylation and hippocampal atrophy which lead to the development of Alzheimeru2019s disease. In human, studies reported deleterious short-term effects of sugars on cognitive performance. However, the long-term effects of high sugars consumption on the brain is unknown. Our study investigated the relationships between glycaemic-load diet and the onset of dementia and Alzheimeru2019s disease. We further investigated potential interaction between glycaemic load and Apolipoprotein E4 allele (APOE4), the strongest genetic risk factor of Alzheimeru2019s disease. Participants from the Three-City cohort completed a validated semi-quantitative Food Frequency Questionnaire which was used to calculate glycaemic load for each meal and snack. Clinical diagnosis of dementia was made at each follow-up (every 2-3 years during 12 years) and analysed using Cox proportional hazards regression models. A total of 2,777 participants were included in the analyses. The participants averaged 75.9 years old and 61.1% were female. During a 12-year follow-up period, 350 participants had dementia (60 had Alzheimeru2019s disease). After controlling for all potential confounders, we found no association between meal glycaemic load and dementia. However, we found a significant interaction between afternoon-snack glycaemic load and APOE4 (HR = 1.27 [1.03-1.56]). This interaction was predictive of Alzheimeru2019s disease (HR = 1.39 [1.05-1.84]) and all dementia type taken together (HR = 1.27 [1.03-1.56]). Moreover, the exclusion of type 2 diabetes cases did not modify our results. This study is the first to highlight, that high-glycaemic-load diet is associated with higher risk of dementia in APOE4 carriers. Targeting sugars consumption could provide clues on Alzheimeru2019s disease physiopathology and avenues for prevention strategies.Conflict of interest:There is no conflict of interest.