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


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


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


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


RESULTS
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.


BACKGROUND
Dutch Trial Register NTR1975.
Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Hanneke
H
de Waal
Department of Clinical Neurophysiology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Cornelis J
CJ
Stam
Nutricia Research, Utrecht, The Netherlands.
Marieke M
MM
Lansbergen
Nutricia Research, Utrecht, The Netherlands.
Rico L
RL
Wieggers
Nutricia Research, Utrecht, The Netherlands.
Patrick J G H
PJ
Kamphuis
Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Philip
P
Scheltens
Laboratory of Cognitive and Computational Neuroscience, UCM-UPM Center for Biomedical Technology, Madrid, Spain.
Fernando
F
Maestú
Department of Clinical Neurophysiology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands ; Nutricia Research, Utrecht, The Netherlands.
Elisabeth C W
EC
van Straaten
D000368:Aged; D000544:Alzheimer Disease / Q000178:diet therapy*; D001921:Brain / Q000187:drug effects*; D002794:Choline; D060825:Cognitive Dysfunction / Q000178:diet therapy*; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D004569:Electroencephalography; D005492:Folic Acid; D005526:Food, Formulated / Q000032:analysis*; D006801:Humans; D016013:Likelihood Functions; D008875:Middle Aged; D009415:Nerve Net / Q000187:drug effects*; D010743:Phospholipids; D012044:Regression Analysis; D012643:Selenium; D013569:Synapses / Q000187:drug effects*; D016896:Treatment Outcome; D014542:Uridine Monophosphate; D014815:Vitamins
D010743:Phospholipids; D014815:Vitamins; D004281:Docosahexaenoic Acids; D005492:Folic Acid; D015118:Eicosapentaenoic Acid; D014542:Uridine Monophosphate; D012643:Selenium; D002794:Choline