P2-437: Supporting synapse formation and function in Alzheimer's disease: Mechanism of action of the specific nutrient combination Fortasyn™ Connect

Alzheimer's disease (AD) is a progressive neurodegenerative disease, leading to gradual decline in cognitive and behavioral function. Although the etiology of AD is unknown, it is recognized that synaptic loss is the strongest structural correlate with memory impairment, the classical clinical feature of AD. Synapses and neurites consist of neuronal membranes largely composed of phosphatides. Synthesis of phosphatides depends on the presence of the dietary precursors DHA, UMP and choline. Additionally, B-vitamins, phospholipids and antioxidants are co-factors in the synthesis pathway of neuronal membranes, e.g. by elevating precursor plasma levels. Several epidemiological studies suggest that low intake of n-3 fatty acids, B-vitamins, and antioxidants increase risk of AD. Furthermore, many other studies suggest that patients with AD have lower plasma levels of these nutrients compared to age-matched controls. Administration of DHA, UMP and choline in experimental animals synergistically increased brain phosphatides, synaptic proteins, and dendritic spines formation (Wurtman, 2009). Supplementation with combinations of DHA and EPA, UMP, choline, B-vitamins, phospholipids and vitamin C and E and selenium showed increased muscarinic receptor density in plasma membranes and enhanced receptor-mediated G-protein activation. In addition, supplementation increased mRNA expression of synaptic proteins related to neurite outgrowth and synapse formation. Furthermore, intervention with the combination of these nutrients improved learning and memory in animal models. Based on these insights the specific nutrient combination Fortasyn Connect (UMP, DHA, EPA, choline, vitamins B6 and B12, folate, phospholipids, vitamin C and E, and selenium) was designed to support synapse formation and function in patients with AD. The effect of Souvenaid ®, a nutritional intervention containing Fortasyn Connect, on memory and cognitive performance was recently assessed in a proof-of-concept study, Souvenir I, with 212 drug-naive mild AD patients (MMSE 20-26). The study showed that Souvenaid given for 12 weeks improves memory in mild drug-naive AD patients (Scheltens, 2010). To confirm and extend these findings, three additional studies were initiated. Two studies were completed in 2011 and one will be completed in 2014.