Sarah Shizuko Morimoto

Cognitive impairment in late‐life depression is prevalent, disabling, and heterogeneous. Although mild cognitive impairment in depression does not usually progress to dementia, accurate assessment of cognition is vital to prognosis and treatment planning. For example, executive dysfunction often accompanies late‐life depression, influences performance across cognitive domains, and is associated with poor antidepressant treatment outcomes. Here, we review how assessment can capture dysfunction across cognitive domains and discuss cognitive trajectories frequently observed in late‐life depression in the context of the neurobiology of this disorder. We also review the efficacy of a sample of interventions tailored to specific cognitive profiles.

Executive dysfunction (ED) in geriatric depression (GD) is common, predicts poor clinical outcomes and often persists despite remission of symptoms. Here we develop a neuroplasticity-based computerized cognitive remediation-geriatric depression treatment (nCCR-GD) to target ED in GD. Our assumption is that remediation of these deficits may modulate the underlying brain network abnormalities shared by ED and depression. We compare nCCR-GD to a gold-standard treatment (escitalopram: 20 mg per 12 weeks) in 11 treatment-resistant older adults with major depression; and 33 matched historical controls. We find that 91% of participants complete nCCR-GD. nCCR-GD is equally as effective at reducing depressive symptoms as escitalopram but does so in 4 weeks instead of 12. In addition, nCCR-GD improves measures of executive function more than the escitalopram. We conclude that nCCR-GD may be equally effective as escitalopram in treating GD. In addition, nCCR-GD participants showed greater improvement in executive functions than historical controls treated with escitalopram.

Late-life depression is often accompanied by cognitive impairment. In some cases, the syndromes of depression and cognitive impairment may be related to the same underlying disorder (eg, vascular dementia, hypothyroidism), whereas in other cases, they may be relatively independent and simply coexist. Cognitive deficits in late-life depression span multiple domains; however, deficits in executive functions may be particularly important as their presence predicts poor clinical outcomes. Cognitive impairment, when mild, does not appear to progress to dementia in most cases, but variability in the course of elders with depression and cognitive impairment suggests the need for careful follow-up, particularly in cases where executive dysfunction is suspected. The Expert Consensus Guideline recommends antidepressant drug therapy combined with a psychosocial intervention as the treatment of choice for geriatric depression. New treatments including computerized cognitive remediation and problem-solving therapy may be particularly effective in treating both affective and cognitive symptoms.

Objective This article describes a novel treatment model designed to target specific neurocognitive deficits in geriatric depression with neuroplasticity-based computerized cognitive remediation (NBCCR). Method The recent National Institute of Mental Health (NIMH) report “From Discovery to Cure” calls for studies focusing on mechanisms of treatment response with the goal of arriving at new interventions for those who do not respond to existing treatments. We describe the process that led to the identification of specific executive deficits and their underlying neurobiology, as well as the rationale for targeting these symptoms as a part of a strategy intended to improve both executive dysfunction and depression. We then propose a strategy for further research in this emerging area Results and Conclusions Despite significant developments, conventional antidepressant treatments leave many older adults still depressed and suffering. Psychotherapy may be effective in some depressed elders, although a recent review concluded that none of the available treatment studies meets stringent criteria for efficacy in the acute treatment of geriatric depression. Appropriately developed and targeted NBCCR, has the potential to serve as a novel treatment intervention for geriatric depression. Pathophysiological changes associated with executive dysfunction may be an appropriate target for NBCCR. Examining both behavioral changes and indices of structural integrity and functional change of networks related to cognitive and emotional regulation may lead to a novel treatment and elucidate the role of specific cerebral networks in geriatric depression. Copyright © 2012 John Wiley & Sons, Ltd.

Objective This study tests the hypothesis that the use of semantic organizational strategy during the free‐recall phase of a verbal memory task predicts remission of geriatric depression. Methods Sixty‐five older patients with major depression participated in a 12‐week escitalopram treatment trial. Neuropsychological performance was assessed at baseline after a 2‐week drug washout period. The Hopkins Verbal Learning Test‐Revised was used to assess verbal learning and memory. Remission was defined as a Hamilton Depression Rating Scale score of ≤7 for 2 consecutive weeks and no longer meeting the DSM‐IV‐TR criteria for major depression. The association between the number of clusters used at the final learning trial (trial 3) and remission was examined using Cox's proportional hazards survival analysis. The relationship between the number of clusters utilized in the final learning trial and the number of words recalled after a 25‐min delay was examined in a regression with age and education as covariates. Results Higher number of clusters utilized predicted remission rates (hazard ratio, 1.26 (95% confidence interval, 1.04–1.54); χ² = 4.23, df = 3, p = 0.04). There was a positive relationship between the total number of clusters used by the end of the third learning trial and the total number of words recalled at the delayed recall trial (F(3,58) = 7.93; p < 0.001). Conclusions Effective semantic strategy use at baseline on a verbal list learning task by older depressed patients was associated with higher rates of remission with antidepressant treatment. This result provides support for previous findings indicating that measures of executive functioning at baseline are useful in predicting antidepressant response. Copyright © 2011 John Wiley & Sons, Ltd.