Hanneke de Waal

Efficacy of souvenaid in mild alzheimer's disease: Results from a randomized, controlled trial

Souvenaid aims to improve synapse formation and function. An earlier study in patients with Alzheimers disease (AD) showed that Souvenaid increased memory performance after 12 weeks in drug-naïve patients with mild AD. The Souvenir II study was a 24-week, randomized, controlled, double-blind, parallel-group, multi-country trial to confirm and extend previous findings in drug-naïve patients with mild AD. Patients were randomized 1:1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. The primary outcome was the memory function domain Z-score of the Neuropsychological Test Battery (NTB) over 24 weeks. Electroencephalography (EEG) measures served as secondary outcomes as marker for synaptic connectivity. Assessments were done at baseline, 12, and 24 weeks. The NTB memory domain Z-score was significantly increased in the active versus the control group over the 24-week intervention period (p = 0.023; Cohens d = 0.21; 95% confidence interval [-0.06]-[0.49]). A trend for an effect was observed on the NTB total composite z-score (p = 0.053). EEG measures of functional connectivity in the delta band were significantly different between study groups during 24 weeks in favor of the active group. Compliance was very high (96.6% [control] and 97.1% [active]). No difference between study groups in the occurrence of (serious) adverse events. This study demonstrates that Souvenaid is well tolerated and improves memory performance in drug-naïve patients with mild AD. EEG outcomes suggest that Souvenaid has an effect on brain functional connectivity, supporting the underlying hypothesis of changed synaptic activity.

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. 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.

Young Alzheimer patients show distinct regional changes of oscillatory brain dynamics

The objective of this study was to examine the differences in oscillatory brain dynamics in Alzheimers disease (AD) according to age at onset using quantitative electroencephalography (EEG). We examined resting state electroencephalograms of 320 probable AD patients and 246 controls, both categorized into a young (≤ 65 years) and old (> 65 years) group. Relative power in 4 different frequency bands was calculated. The effect of age on global and regional relative power was examined. Globally, young AD patients showed lower alpha- and higher delta-power than old AD patients. Regional analysis showed that these differences were most pronounced in the parieto-occipital region. Young AD patients had lower beta- and higher theta-power than old patients in all but the temporal regions. In controls, there was no age effect on global relative power in any frequency band. Young AD patients present with more severe slowing of spontaneous oscillatory activity than old AD patients, which is most pronounced in the posterior brain areas. This finding supports the hypothesis that early onset AD presents with a distinct endophenotype.

Loss of EEG Network Efficiency Is Related to Cognitive Impairment in Dementia With Lewy Bodies

The aim of this study was to test whether disturbed EEG resting‐state functional connectivity and network organization are a potential neurophysiological substrate of cognitive impairment in dementia with Lewy bodies.

Disturbed oscillatory brain dynamics in subcortical ischemic vascular dementia

BackgroundWhite matter hyperintensities (WMH) can lead to dementia but the underlying physiological mechanisms are unclear. We compared relative oscillatory power from electroencephalographic studies (EEGs) of 17 patients with subcortical ischemic vascular dementia, based on extensive white matter hyperintensities (SIVD-WMH) with 17 controls to investigate physiological changes underlying this diagnosis.ResultsDifferences between the groups were large, with a decrease of relative power of fast activity in patients (alpha power 0.25 ± 0.12 versus 0.38 ± 0.13, p = 0.01; beta power 0.08 ± 0.04 versus 0.19 ± 0.07; p<0.001) and an increase in relative powers of slow activity in patients (theta power 0.32 ± 0.11 versus 0.14 ± 0.09; p<0.001 and delta power 0.31 ± 0.14 versus 0.23 ± 0.09; p<0.05). Lower relative beta power was related to worse cognitive performance in a linear regression analysis (standardized beta = 0.67, p<0.01).ConclusionsThis pattern of disturbance in oscillatory brain activity indicate loss of connections between neurons, providing a first step in the understanding of cognitive dysfunction in SIVD-WMH.

Alzheimer's disease patients not carrying the apolipoprotein E ε4 allele show more severe slowing of oscillatory brain activity.

The objective of this study was to quantitatively assess the relationship between apolipoprotein (APOE) genotype and electroencephalographic oscillatory brain dynamics in Alzheimers disease (AD) patients and control subjects and its regional distribution. We obtained resting-state electroencephalographs of 320 AD patients and 246 control subjects, categorized into APOE ε4 carriers and noncarriers. Peak frequency and relative power in 4 different frequency bands were calculated. We tested the associations between APOE genotype and relative power in 4 brain regions. Peak frequency was comparable in APOE ε4 carrying and noncarrying control subjects, but lower in APOE ε4 noncarrying AD patients. In control subjects, APOE ε4 carriers had a different regional distribution of alpha power than noncarriers. We found no APOE effect in beta, delta, and theta bands. In AD, APOE ε4 noncarriers had lower alpha and higher delta power than carriers. This difference was most pronounced in the parieto-occipital region. In the theta band, APOE ε4 noncarriers had a different regional distribution of power compared with carriers. In conclusion, the most pronounced effect of genotype was seen in AD patients, and APOE ε4 noncarriers showed slower activity, especially in parieto-occipital regions.

EEG DIRECTED CONNECTIVITY FROM POSTERIOR BRAIN REGIONS IS DECREASED IN DEMENTIA WITH LEWY BODIES: A COMPARISON WITH ALZHEIMER’S DISEASE AND CONTROLS

not available. SATURDAY, JULY 23, 2016 ALZHEIMER’S IMAGING CONSORTIUM (AIC) ICI-02 ALZHEIMER’S DISEASE IMAGING BIOMARKERS AND AGING ICI-02-01 ALZHEIMER’S DISEASE IMAGING BIOMARKERS AND AGING Clifford R. Jack Jr, Mayo Clinic, Rochester, MN, USA. Contact e-mail: jack.clifford@mayo.edu Abstract not available.not available. SATURDAY, JULY 23, 2016 ALZHEIMER’S IMAGING CONSORTIUM (AIC) ICI-03 CONTROVERSY DEBATE: ALZHEIMER’S DISEASE — SINGLE VERSUS MULTIPLE BRAIN NETWORK DISORDER ICI-03-01 CONTROVERSY DEBATE: SINGLE BRAIN NETWORK DISORDER Christian Sorg, University Hospital Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. Contact e-mail: c.sorg@lrz.

An eeg study into functional connectivity and hubs in Alzheimer’s disease: What’s going on in the posterior regions?

Figure. Differ olism (C) betw works in Mild PCC network three modaliti and disruption HYPOMETABOLISM, AND ATROPHY BETWEEN VENTRAL AND DORSAL POSTERIOR CINGULATE CORTEX NETWORKS IN MILD COGNITIVE IMPAIRMENTAND ALZHEIMER’S DISEASE Justine Mutlu, Robin de Flores, Cl emence Tomadesso, Brigitte Landeau, Florence M ezenge, Vincent de La Sayette, Francis Eustache, Ga€el Ch etelat, Inserm-EPHE-UCBN U1077, Caen, France; Inserm-EPHE-UCBN U1077, Caen, France; Inserm-EPHE-UCBN U1077-CHU de Caen, Caen, France; CHU de Caen, U1077, Caen, France. Contact e-mail: mutlu@cyceron.fr

Age-related differences in functional connectivity of resting-state EEGs in Alzheimer's disease

tract (CST), and right superior longitudinal fasciculus (Fig. 1). As shown by the ROI analysis (Table 1), decreased AFD was observed in all structures except the CSTwhen comparing AD vs MCI, but only in the left cingulum, uncinate, and CSTwhen comparing MCI vs healthy subjects. Conclusions: We demonstrated extensive AFD decreases in AD vs healthy subjects in white matter bundles known to be involved in language and memory. These were more extensive (particularly in the cingulum and uncinate) than have been reported using previous DWI metrics. Most of the affected regions were also different between MCI vs AD, with some regions also significant in MCI vs healthy. AFD provides improved specificity by identifying which particular WM tract is affected even in regions traversed by multiple fibre bundles (Fig. 1h&i). [1] Raffelt et al. (in press)doi:10.1016/j.neuroimage. 2011.10.045.