A multi nutrient concept to enhance synapse formation and function: science behind a medical food for Alzheimer’s disease

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder and is the leading cause of dementia. In 2010, there were an estimated 35.6 million AD sufferers worldwide and, with the global ageing population, the estimate is expected to increase to 115.4 million by 2050 (ADI, 2010). Age is the primary risk factor (von Strauss et al., 1999; Citron, 2002), while the primary genetic risk factors include family history of AD (for familial AD) and presence of the apolipoprotein E-e4 genotype (apoE4, for sporadic AD) (Fratiglioni et al., 1993; Seshadri et al., 1995). Furthermore, increasing epidemiological evidence suggests diet as one of themost importantmodifiable risk factors (Engelhart et al., 2002; Morris et al., 2003).Other aspects of diseaseaetiology, including vascular and psychosocial Abstract: Alzheimer’s Disease (AD) is the leading cause of dementia. Epidemiological studies suggest that AD is linked with poor status of nutrients including DHA, B-vitamins and the vitamins E and C. Ongoing neurodegeneration, particularly synaptic loss, leads to the classical clinical features of AD namely, memory impairment, language deterioration, and executive and visuospatial dysfunction. The main constituents of neural and synaptic membranes are phospholipids. Supplemenation of animals with three dietary precursors of phospholipids namely, DHA, uridine monophosphate and choline, results in increased levels of brain phospholipids, synaptic proteins, neurite outgrowth, dendritic spines formation (i.e. the anatomical precursors of new synapses) and an improvement in learning and memory. Other nutrients act as co-factors in the synthesis pathway of neuronal membranes. For example B-vitamins are involved in methylation processes, thereby enhancing the availability of choline as a synaptic membrane precursor. A multi-nutrient concept that includes these nutrients may improve membrane integrity, thereby influencing membrane-dependent processes such as receptor function and amyloid precursor protein (APP) processing, as shown by reduced amyloid production and amyloid b plaque burden, as well as toxicity. Together, these insights provided the basis for the development of a medical food for patients with AD, Souvenaid, containing a specific combination of nutrients (Fortasyn Connect) and designed to enhance synapse formation in AD. The effect of Souvenaid on memory and cognitive performance was recently assessed in a proof-of-concept study, SOUVENIR I, with 212 drug-naı̈ve mild AD patients (MMSE 20-26). This proof-of-concept study demonstrated that oral nutritional supplementation with Souvenaid1 for 12 weeks improves memory in patients with mild AD. To confirm and extend these findings, we have designed and initiated three additional studies. Two of these studies will be completed in 2011; Souvenir II, a 24-week European study, with 259 drug-naı̈ve mild AD patients (MMSE 20) and S-Connect, another 24-week study, with 527 mild-tomoderate AD patients (MMSE 14-24) using AD medication conducted in the US. The third is the EU-funded LipiDiDiet study, a 24-month study, which will enrol 300 people with prodromal AD to assess the effect on memory performance.