The LipiDiDiet study in prodromal AD (Dubois 2007) investigates the long-term effects of a specific nutritional intervention (Souvenaid) targeting the formation and function of neuronal membranes and synapses. The rationale for this study is based on effects of specific nutrient enrichment in basic science models and clinical trials in AD.
Synaptic loss has been recognized as strongest structural correlate with memory impairment in AD and is apparent already early in the disease, including MCI. Synapses largely consist of neuronal membranes which are mainly composed of phospholipids. Phospholipid synthesis depends on the availability of rate limiting nutritional precursors and cofactors. Basic science studies indicate that their increased intake enhances synaptogenesis. However, lower plasma levels of these nutrients are widely observed in AD, eg lower levels of uridine and docosahexaenoic acid are found in early AD patients compared with controls.
Recent preclinical studies in the LipiDiDiet project confirmed beneficial effects of the intervention on cognitive performance and neuroimaging markers in a mouse model (APP/PS1) of AD. The clinical studies so far in AD demonstrated that the nutritional intervention is safe and improved memory performance in mild, but not moderate, AD and improved EEG measures of functional connectivity.
Mechanistic and clinical studies suggest potential utility of increasing intake of specific nutrients in the earliest stages of AD. The LipiDiDiet study is designed to test the hypothesis that the investigational intervention Souvenaid improves cognitive outcome and disease markers in prodromal AD.
1Funded by EU FP7 project LipiDiDiet, Grant Agreement N°211696