Photograph of an urban scene.

<p>Photograph of an urban scene.</p

Activity significantly greater for stimuli rated as not beautiful rather than beautiful: 300–400 ms time-window.

<p>Activity significantly greater for stimuli rated as not beautiful rather than beautiful: 300–400 ms time-window.</p

The Effect of Souvenaid on Functional Brain Network Organisation in Patients with Mild Alzheimer’s Disease: A Randomised Controlled Study

<div><p>Background</p><p>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.</p><p>Objective</p><p>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.</p><p>Design</p><p>A 24-week randomised, controlled, double-blind, parallel-group, multi-country study.</p><p>Participants</p><p>179 drug-naïve mild AD patients who participated in the Souvenir II study.</p><p>Intervention</p><p>Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks.</p><p>Outcome</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>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.</p><p>Trial registration</p><p>Dutch Trial Register <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1975" target="_blank">NTR1975</a>.</p></div

Schematic representation of construction of graphs from EEG time series.

<p>EEG time series are measured from scalp electrodes. Phase Lag Index (PLI) as a measure of functional connectivity is calculated between all pairs of electrodes. From the PLI adjacency matrix, the functional brain network is reconstructed and network measures are computed.</p

Baseline demographics and characteristics of the subset of subjects for whom EEG data were available (intent-to-treat population).

<p><i>Note.</i> AD: Alzheimer’s disease; MMSE: Mini-Mental State Examination; Data are presented as mean (standard deviation) unless stated otherwise.</p

Descriptive statistics for the normalised path length lambda (intent-to-treat population).

<p><i>Note.</i> Data are means (standard deviation).</p>1<p><i>P</i>-values were based on a mixed model for repeated measures (2 degrees of freedom contrast) with post-baseline measurements as an outcome.</p