Remediation of Age-related Cognitive Decline: Vortioxetine and Cognitive Training

The purpose of this research study is to examine the potential benefits of vortioxetine in combination with at-home computerized cognitive training program to improve cognition, such as memory, attention, and concentration. This study will compare the effectiveness of vortioxetine plus cognitive training versus placebo plus cognitive training.

The purpose of this research study is to examine the potential benefits of vortioxetine in combination with at-home computerized cognitive training program to improve cognition, such as memory, attention, and concentration. This study will compare the effectiveness of vortioxetine plus cognitive training versus placebo plus cognitive training.

Vortioxetine is considered investigational when used as a treatment for age-related cognitive decline, which means that it has not been approved by the U.S. Food and Drug Administration for this purpose. Vortioxetine is approved by the U.S. Food and Drug Administration as a treatment for depression, and also goes by the name Trintellix (formerly known as Brintellix). That means that, while the drug itself is approved by the FDA, it is not approved for the reasons the investigators are using it in this study.

Participation in this study entails an estimated 6 study visits over the course of approximately six months. Participants will complete various assessments at our lab at the Washington University School of Medicine along with check-in visits in-person or over the phone. Additionally, they will participate in at home computerized cognitive training for approximately six months, supplemented with either vortioxetine or placebo.

The investigators will assess memory and problem-solving abilities using paper and pencil, computerized measures, and self-assessments of how participants feel. These tests could include numbers, letters, symbols, words, or sentences. These tests will be repeated throughout the study. If eligible to do so, participants will complete a baseline MRI scan.

A subset of participants who completed a baseline MRI scan will complete another MRI scan after approximately 26 weeks of vortioxetine or placebo and at home computerized cognitive training.

Eligibility Criteria:
Inclusion Criteria:

* Community-living men and women age 65 and older
* Age-related cognitive decline as defined by (a) self-reported cognitive dysfunction that is attributed to the aging process (in response to screening questions to the participant); (b) ability to complete cognitive battery, but still scoring less than 1 standard deviation above age-matched norms at both baseline and after the two-week cognitive training lead-in.

Exclusion Criteria:

* Known dementia or other clinical neurodegenerative illness (e.g., Parkinson's disease, cerebrovascular disease) per self-report, informant report, medical records, or neuropsychological testing
* Any current psychiatric disorder
* Medical conditions that suggest shortened lifespan, such as metastatic cancer; or would prohibit safe participation in the interventions, including cardiovascular disease or musculoskeletal conditions; or with the assessments.
* Sensory impairment that would prevent participation
* IQ \< 70 as estimated by the Wechsler Test of Adult Reading
* Alcohol or substance abuse within 6 months
* Concurrent cognitive training, such as brain-training software, or other interventions expected to affect neuroplasticity
* Psychotropic medications or those with likely CNS effects (none within 4 weeks prior to study entry)