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Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. Conclusions GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. Trial registration ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014

Objective: To investigate the effectiveness of mirror therapy combined with neuromuscular electrical stimulation in promoting motor recovery of the lower limbs and walking ability in patients suffering from foot drop after stroke. Design: Randomized controlled study. Setting: Inpatient rehabilitation center of a teaching hospital. Subjects: Sixty-nine patients with foot drop. Intervention: Patients were randomly divided into three groups: control, mirror therapy, and mirror therapy + neuromuscular electrical stimulation. All groups received interventions for 0.5 hours/day and five days/week for four weeks. Main measures: 10-Meter walk test, Brunnstrom stage of motor recovery of the lower limbs, Modified Ashworth Scale score of plantar flexor spasticity, and passive ankle joint dorsiflexion range of motion were assessed before and after the four-week period. Results: After four weeks of intervention, Brunnstrom stage (P = 0.04), 10-meter walk test (P < 0.05), and passive range of motion (P < 0.05) showed obvious improvements between patients in the mirror therapy and control groups. Patients in the mirror therapy + neuromuscular electrical stimulation group showed better results than those in the mirror therapy group in the 10-meter walk test (P < 0.05). There was no significant difference in spasticity between patients in the two intervention groups. However, compared with patients in the control group, patients in the mirror therapy + neuromuscular electrical stimulation group showed a significant decrease in spasticity (P < 0.001). Conclusion: Therapy combining mirror therapy and neuromuscular electrical stimulation may help improve walking ability and reduce spasticity in stroke patients with foot drop.

Background/Aims: To investigate whether diffusion tensor imaging (DTI) is more sensitive than conventional MRI at detecting cognitive deterioration in patients with subcortical ischemic vascular disease (SIVD). Methods: Forty-two SIVD patients had a diagnosis of no cognitive impairment (NCI), vascular cognitive impairment/no dementia or vascular dementia (VaD). Whole-brain DTI histography and routine MRI were performed on these participants. Results: There were significant differences between cognitively impaired patients and NCI subjects in mean diffusivity and fractional anisotropy in either whole-brain white matter (WBWM) or in normal-appearing white matter (NAWM). All DTI indices within either WBWM or NAWM were found to be significantly correlated with both the attention-executive and memory measures in SIVD subjects. Lacune numbers and T₂-weighted lesions correlated only with attention-executive measures, whereas hippocampal volumes correlated only weakly with memory measures. Whole-brain gray matter volumes correlated with Z scores for all cognitive domains but language. After VaD patients had been excluded from the analysis, cognitive measures remained significantly correlated with some of the DTI indices, but not with conventional MRI findings. Conclusions: Compared with conventional MRI, whole-brain DTI is a more reliable and sensitive technique for the early detection of cognitive impairment in SIVD patients.