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.

Neurological signs in relation to type of cerebrovascular disease in vascular dementia.

BACKGROUND AND PURPOSE: The aim of this study was to describe the prevalence of a number of neurological signs in a large population of patients with vascular dementia (VaD) and to compare the relative frequency of specific neurological signs dependent on type of cerebrovascular disease. METHODS: Seven hundred six patients with VaD (NINDS-AIREN) were included from a large multicenter clinical trial (registration number NCT00099216). At baseline neurological examination, the presence of 16 neurological signs was assessed. Based on MRI, patients were classified as having large vessel VaD (18%; large territorial or strategical infarcts on MRI), small vessel VaD (74%; white matter hyperintensities [WMH], multiple lacunes, bilateral thalamic lesions on MRI), or a combination of both (8%). RESULTS: A median number of 4.5 signs per patient was presented (maximum 16). Reflex asymmetry was the most prevalent symptom (49%), hemianopia was most seldom presented (10%). Measures of small vessel disease were associated with an increased prevalence of dysarthria, dysphagia, parkinsonian gait disorder, rigidity, and hypokinesia and as well to hemimotor dysfunction. By contrast, in the presence of a cerebral infarct, aphasia, hemianopia, hemimotor dysfunction, hemisensory dysfunction, reflex asymmetry, and hemiplegic gait disorder were more often observed. CONCLUSIONS: The specific neurological signs demonstrated by patients with VaD differ according to type of imaged cerebrovascular disease. Even in people who meet restrictive VaD criteria, small vessel disease is often seen with more subtle signs, including extrapyramidal signs, whereas large vessel disease is more often related to lateralized sensorimotor changes and aphasia.

Thalamic lesions in vascular dementia: low sensitivity of fluid-attenuated inversion recovery (FLAIR) imaging.

BACKGROUND AND PURPOSE: The criteria of the National Institute of Neurological Disorders and Stroke (NINDS)-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) include thalamic lesions for the diagnosis of vascular dementia (VaD). Although studies concerning VaD and brain aging advocate the use of fluid-attenuated inversion recovery (FLAIR) or T2-weighted images (T2-WI) to detect ischemic lesions, none compared the sensitivity of these sequences to depict thalamic lesions. METHODS: We performed a blinded review of T2-WI and FLAIR images in 73 patients fulfilling the radiological part of the NINDS-AIREN criteria (mean age, 71 years; range, 49 to 83 years). This sample was drawn from a large multicenter trial on VaD and was expected to have a high prevalence of thalamic lesions. In a side-by-side review, including T1-weighted images as well, lesions were classified according to presumed underlying pathology. RESULTS: The total number of thalamic lesions was 214. Two hundred eight (97%) were detected on T2-WI, but only 117 (55%) were detected on FLAIR (chi(2)=5.1; P<0.05). Although the mean size of lesions detected on T2-WI and not on FLAIR (4.4 mm) was significantly lower than the mean size of lesions detected on both sequences (6.7 mm) (P<0.001), 5 of the 29 lesions >10 mm on T2-WI were not visible on FLAIR. FLAIR detected only 81 (51%) of the 158 probable ischemic lesions and 30 (60%) of the 50 probable microbleeds. CONCLUSIONS: FLAIR should not be used as the only T2-weighted sequence to detect thalamic lesions in patients suspected of having VaD.