title: Magnetoencephalography for the Detection of Intervention Effects of a Specific Nutrient Combination in Patients with Mild Alzheimer's Disease: Results from an Exploratory Double-Blind, Randomized, Controlled Study.
abstract: Synaptic loss is an early pathological finding in Alzheimer's disease (AD) and correlates with memory impairment. Changes in macroscopic brain activity measured with electro- and magnetoencephalography (EEG and MEG) in AD indicate synaptic changes and may therefore serve as markers of intervention effects in clinical trials. EEG peak frequency and functional networks have shown, in addition to improved memory performance, to be sensitive to detect an intervention effect in mild AD patients of the medical food Souvenaid containing the specific nutrient combination Fortasyn®Connect, which is designed to enhance synapse formation and function. Here, we explore the value of MEG, with higher spatial resolution than EEG, in identifying intervention effects of the nutrient combination by comparing MEG spectral measures, functional connectivity, and networks between an intervention and a control group. Quantitative markers describing spectral properties, functional connectivity, and graph theoretical aspects of MEG from the exploratory 24-week, double-blind, randomized, controlled Souvenir II MEG sub-study (NTR1975, http://www.trialregister.nl) in drug naïve patients with mild AD were compared between a test group (n= 27), receiving Souvenaid, and a control group (n= 28), receiving an isocaloric control product. The groups were unbalanced at screening with respect to Mini-Mental State Examination. Peak frequencies of MEG were compared with EEG peak frequencies, recorded in the same patients at similar time points, were compared with respect to sensitivity to intervention effects. No consistent statistically significant intervention effects were detected. In addition, we found no difference in sensitivity between MEG and EEG peak frequency. This exploratory study could not unequivocally establish the value of MEG in detecting interventional effects on brain activity, possibly due to small sample size and unbalanced study groups. We found no indication that the difference could be attributed to a lack of sensitivity of MEG compared with EEG. MEG in randomized controlled trials is feasible but its value to disclose intervention effects of Souvenaid in mild AD patients needs to be studied further.
authors: Department of Clinical Neurophysiology, MEG Center, VU Medical Center, Amsterdam, Netherlands; Nutricia Advanced Medical Nutrition, Nutricia Research, Utrecht, Netherlands.
authors: Elisabeth C W
authors: EC
authors: van Straaten
authors: Department of Neurology, Alzheimer Center, VU Medical Center , Amsterdam , Netherlands.
authors: Hanneke
authors: H
authors: de Waal
authors: Nutricia Advanced Medical Nutrition, Nutricia Research , Utrecht , Netherlands.
authors: Marieke M
authors: MM
authors: Lansbergen
authors: Department of Neurology, Alzheimer Center, VU Medical Center , Amsterdam , Netherlands.
authors: Philip
authors: P
authors: Scheltens
authors: Laboratory of Cognitive and Computational Neuroscience (UCM-UPM), Center for Biomedical Technology , Madrid , Spain.
authors: Fernando
authors: F
authors: Maestu
authors: Magnetoencephalography Unit, Centro Medico Teknon , Barcelona , Spain.
authors: Rafal
authors: R
authors: Nowak
authors: Department of Clinical Neurophysiology, MEG Center, VU Medical Center , Amsterdam , Netherlands.
authors: Arjan
authors: A
authors: Hillebrand
authors: Department of Clinical Neurophysiology, MEG Center, VU Medical Center , Amsterdam , Netherlands.
authors: Cornelis J
authors: CJ
authors: Stam
keywords: Alzheimer’s disease; brain networks; clinical trial; magnetoencephalography; medical nutrition