Effects of Vortioxetine in MCI measured by fMRI

Mild cognitive impairment (MCI) is a syndrome characterized by cognitive deficits (e.g. memory impairment) beyond that expected for age and education. MCI is considered an early stage of dementia (especially Alzheimers dementia) in the continuum between normal aging and the manifest illness stage. In this study we examine the pharmacological effects of vortioxetine, which is a novel antidepressant that has been licensed for the treatment of major depressive disorder since 2013, on cognitive functioning in patients suffering from MCI. This drug has been shown to enhance cognitive performance in patients with major depressive disorder in several studies. Improvements have been found in particular in executive functioning, attention, processing speed, and memory. The role of vortioxetine in the treatment of MCI and the specific pathophysiological implications of this treatment have not been investigated before. We therefore propose to measure the effects of vortioxetine on brain functional connectivity (the functional relationship between separated areas of the brain) with functional magnetic resonance imaging (fMRI) in a sample of MCI patients and to provide data on the efficiency and tolerability of vortioxetine in MCI. Therefore, we have planned a randomized, double-blind, placebo-controlled trial on vortioxetine 10mg or 20mg or placebo in 45 MCI patients over 12 weeks with 7 study visits. Neuroimaging with fMRI will be carried out three times in all study subjects at week 0, 4, and 12. The participants will undergo several neuropsychological assessments during the course of the study to assess the cognitive effects of the drug. Side effects will be assessed regularly during every visit after start of vortioxetine intake. End of study evaluations will be performed in week 12. We expect significant drug effects on cognitive performance as well as on brain functional connectivity during this time frame, as prior studies with vortioxetine in depressed patients have found significant improvements in cognition within 8 weeks.