The effect of souvenaid on functional brain network organisation in patients with mild Alzheimer's disease: a randomised controlled study

PLoS One. 2014 Jan 27;9(1):e86558. doi: 10.1371/journal.pone.0086558. eCollection 2014.

Abstract

Background: Synaptic loss is a major hallmark of Alzheimer's disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials.

Objective: To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD.

Design: A 24-week randomised, controlled, double-blind, parallel-group, multi-country study.

Participants: 179 drug-naïve mild AD patients who participated in the Souvenir II study.

Intervention: Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks.

Outcome: In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance.

Results: THE NETWORK MEASURES IN THE BETA BAND WERE SIGNIFICANTLY DIFFERENT BETWEEN GROUPS: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance.

Conclusions: The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions.

Trial registration: Dutch Trial Register NTR1975.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / diet therapy*
  • Brain / drug effects*
  • Choline
  • Cognitive Dysfunction / diet therapy*
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Electroencephalography
  • Folic Acid
  • Food, Formulated / analysis*
  • Humans
  • Likelihood Functions
  • Middle Aged
  • Nerve Net / drug effects*
  • Phospholipids
  • Regression Analysis
  • Selenium
  • Synapses / drug effects*
  • Treatment Outcome
  • Uridine Monophosphate
  • Vitamins

Substances

  • Phospholipids
  • Vitamins
  • Docosahexaenoic Acids
  • Folic Acid
  • Eicosapentaenoic Acid
  • Uridine Monophosphate
  • Selenium
  • Choline

Grant support

Study design and planning were carried out in conjunction with the sponsor, Danone Research BV, on behalf of Nutricia Advanced Medical Nutrition, Danone’s specialised healthcare unit. The sponsor also provided the study products and funding for the research and data collection. Statistical analysis was conducted by staff of Danone Research. The Souvenir II study was supported by the NL Food & Nutrition Delta project, FND N°10003 (http://www.foodnutritiondelta.nl).