The LipiDiDiet trial: what does it add to the current evidence for Fortasyn Connect in early Alzheimer's disease?

Nutritional factors can influence the risk of developing Alzheimer's disease (AD) and its rate of progression, and there is, therefore, increasing interest in nutrition as a modifiable risk factor for the disease. Synaptic loss is an important feature of early AD, and the formation of new synapses is dependent on key nutritional elements that are known to be deficient in patients with AD. The daily medical food, Souvenaid, contains Fortasyn Connect, a multinutrient combination developed to specifically address these deficiencies, comprising docosahexaenoic acid, eicosapentaenoic acid, uridine monophosphate, choline, phospholipids, selenium, folic acid, and vitamins B12, B6, C, and E. Although yielding heterogeneous findings, clinical studies of Fortasyn Connect provide preliminary evidence of clinically relevant benefits on cognitive outcomes in prodromal and early AD. The LipiDiDiet trial investigated the effects of Fortasyn Connect on cognition and related measures in prodromal AD, and is the first randomized, controlled, double-blind, multicenter trial study of a non-pharmacological intervention in this setting. The primary efficacy endpoint was change over 24 months in a composite score of cognitive performance using a neuropsychological test battery. Fortasyn Connect had no significant effect on this endpoint, but demonstrated a significant benefit on secondary endpoints, including domains of cognition affected by AD (attention, memory, executive function) and hippocampal atrophy, suggesting a potential benefit on disease progression. Other studies have demonstrated benefits for Fortasyn Connect on nutritional markers and levels of plasma homocysteine. Taken together, current evidence indicates that Fortasyn Connect may show benefit on domains of cognition affected by AD and nutritional measures that influence risk factors for its progression; that it has greater potential for benefit earlier rather than later in the disease; and that it is safe and well tolerated, alone or in combination with AD medications. Further research into its potential role in AD management is therefore warranted.