Contemporary methods of improving cognitive dysfunction in clinical depression

ABSTRACT

Introduction: Cognitive dysfunction is prevalent in patients with major depressive disorder (MDD), with deficits observed across several domains (e.g., executive function, memory, attention). While depression alone is disabling, patients with cognitive deficits typically experience greater functional impairments, poorer clinical recovery, and reduced quality of life. Consequently, it is imperative to elucidate recent advances in our understanding of the treatment of cognitive dysfunction in MDD.

Areas covered: This review spans psychological, physical, and pharmacological treatment approaches for cognitive dysfunction in depression. Where possible, the authors summarise where treatments have demonstrated efficacy in improving specific cognitive domains (e.g., attention), and highlight the differential mechanisms which underpin cognitive improvement. In addition, the roles of adjunctive cognitive treatments (e.g., exercise), and the possible side effects and drawbacks of specific treatments are explored.

Expert opinion: Psychological treatments typically confer cognitive improvement alongside functional and/or clinical recovery; however, the efficacy of cognitive training and cognitive behavioral therapy to longitudinal cognitive improvement remains to be established. Recently developed pharmacological agents may improve cognition by reducing low-grade inflammation and promoting neurogenesis; however, the pro-cognitive effects of typical antidepressants are limited. Integrated approaches which emphasize cognitive recovery alongside clinical and functional improvement may be key to advancing patient outcomes.

KEYWORDS:

• Cognition
• depression
• MDD
• treatment
• cognitive training
• antidepressant
• exercise

Article highlights

• Cognitive dysfunction is prevalent in patients with Major Depressive Disorder (MDD), and is associated with poor clinical recovery and psychosocial dysfunction.

• Cognition is often considered a secondary outcome, resulting in an unstandardized measurement of cognitive performance and few high-quality clinical trials for treating cognitive deficits.

• Cognitive training appears to enhance cognitive performance, with some studies demonstrating the transfer of these improvements to occupational and social outcomes.

• While inconsistently reported, Cognitive Behavioural Therapy appears to improve to cognitive flexibility.

• Literature on exercise and cognition in MDD is limited by the conflation of physical, psychological, and behavioral changes associated with exercise programs. Accordingly, it is currently unknown whether exercise improves cognition via a direct effect on brain function, or indirectly by encouraging positive behavior and psychological strategies.

• Current reviews of cognition and anti-depressants demonstrate mixed results, with a modest benefit to delayed memory. In addition, Vortioxetine appears generally beneficial to psychomotor speed. The unique benefit of Vortioxetine may be mediated by increases in glutamate neurotransmission and neuroplasticity associated with cognitive dysfunction. Future work should investigate these mechanisms of action, potentially expanding other treatments to target similar neurological functions.

• While inflammatory markers are associated with cognitive dysfunction, research on clinical efficacy for improving cognition by anti-inflammatory medication and PUFAs remains at the early stages. More studies are needed to investigate the role of anti-inflammatories as both a standalone and augmentation treatment strategy.

• While there is significant diversity in the methodology of rTMS studies, positive effects in a number of cognitive domains are typically reported. Much less literature is available for the pro-cognitive effects of tDCS, with available work suggesting enhancement of working memory. While neurostimulation is a promising area, more work is needed to investigate the acute and long-term effect of these strategies on cognition in depressed patients.

Declaration of interest

B Baune has received speaker/consultation fees from: AstraZeneca, Lundbeck, Pfizer, Takeda, Servier, Bristol-Myers Squibb, Otsuka, and Janssen-Cilag. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Notes

1. ‘Global cognition’ refers to broad cognitive abilities spanning a number of domains.

Additional information

Funding

This review was funded by an unrestricted grant from the James and Diana Ramsay Foundation. The funder had no impact on the content of the current work.