Sarah Shizuko Morimoto

THE INFLAMMATION HYPOTHESIS IN GERIATRIC DEPRESSION

A large body of research has focused on “mediating mechanisms” and predisposing brain abnormalities to geriatric depression, but little is known about its etiology. This paper examines whether age‐related and comorbid disease‐related immune deregulation is an etiologic contributor to geriatric depression.

BDNF Val66met Polymorphism, White Matter Abnormalities and Remission of Geriatric Depression

OBJECTIVE The polymorphism BDNF val66met of the brain derived neurotrophic factor (BDNF) is common, may increase the risk for depression, and affects BDNF secretion, critical for neuronal survival, plasticity, neurogenesis, and synaptic connectivity. Our objectives were: 1) to test the hypothesis that BDNF(val/met) status influences the remission rate of geriatric depression; 2) to explore whether the relationship between BDNF allelic status to remission is influenced by the presence of microstructural white matter abnormalities. METHOD Non-demented older subjects with major depression had a 2-week placebo period, after which those with a Hamilton Depression Rating Scale (HDRS) of 18 or greater received escitalopram 10 mg daily for 12 weeks. Fractional anisotropy was determined in specific regions using the Reproducible Object Quantification Scheme (ROQS) software that operates on non-normalized data. RESULTS BDNF(met) carriers were more likely to achieve remission than BDNF(val/val) homozygotes after 12 weeks of treatment with escitalopram 10 mg daily. Microstructural abnormalities in the corpus callosum, left superior corona radiata, and right inferior longitudinal fasciculum were also associated with lower remission rate. However, there were no significant interactions between BDNF(val66met) status and microstructural abnormalities in predicting remission. LIMITATIONS Small number of subjects, focus on a single BDNF polymorphism, fixed antidepressant dose. CONCLUSIONS Depressed older BDNF(met) carriers had a higher remission rate than BDNF(val/val) homozygotes. This effect was not related to microstructural white matter abnormalities, which predicted remission independently. We speculate that the relationship between BDNF(val66met) and remission is due to different effects of BDNF in brain structures related to mood regulation.

Executive dysfunction and treatment response in late-life depression

Executive dysfunction in geriatric depression has been shown to predict poor response to antidepressant medication. The purpose of this review is to clarify which aspects of executive functioning predict poor antidepressant treatment response.

Cognitive deficits in geriatric depression: clinical correlates and implications for current and future treatment.

The purpose of this article is to identify the cognitive deficits commonly associated with geriatric depression and describe their clinical significance. The complex relationship between geriatric depression and dementia is summarized and possible shared mechanisms discussed. Evidence regarding whether the cognitive deficits in depression may be mitigated with medication or with computerized cognitive remediation is presented.

Semantic organizational strategy predicts verbal memory and remission rate of geriatric depression

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.

Diagnosis and treatment of depression and cognitive impairment in late life

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.

Neuroplasticity-based computerized cognitive remediation for treatment-resistant geriatric depression.

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 treatment (CCR-GD) to target ED in GD. Our assumption is that remediation of these deficits may modulate the underlying brain network abnormalities shared by executive dysfunction and depression. We compare CCR-GD to a gold standard treatment (escitalopram: 20mgs/12 weeks) in 11 treatment resistant older adults with major depression; and 33 matched historical controls. We find that 91% of participants complete CCR-GD. CCR-GD is equally as effective at reducing depressive symptoms as escitalopram but does so in 4 weeks instead of 12. In addition CCR-GD improves measures of executive function more than the escitalopram. We conclude that CCR-GD may be equally effective as escitalopram in treating GD. In addition, CCR-GD participants showed greater improvement in executive functions than historical controls treated with escitalopram.

Executive Functioning Complaints and Escitalopram Treatment Response in Late-Life Depression

OBJECTIVE Executive dysfunction may play a key role in the pathophysiology of late-life depression. Executive dysfunction can be assessed with cognitive tests and subjective report of difficulties with executive skills. The present study investigated the association between subjective report of executive functioning complaints and time to escitalopram treatment response in older adults with major depressive disorder (MDD). METHODS 100 older adults with MDD (58 with executive functioning complaints and 42 without executive functioning complaints) completed a 12-week trial of escitalopram. Treatment response over 12 weeks, as measured by repeated Hamilton Depression Rating Scale scores, was compared for adults with and without executive complaints using mixed-effects modeling. RESULTS Mixed effects analysis revealed a significant group × time interaction, F(1, 523.34) = 6.00, p = 0.01. Depressed older adults who reported executive functioning complaints at baseline demonstrated a slower response to escitalopram treatment than those without executive functioning complaints. CONCLUSION Self-report of executive functioning difficulties may be a useful prognostic indicator for subsequent speed of response to antidepressant medication.

Neuroplasticity‐based computerized cognitive remediation for geriatric depression

This article describes a novel treatment model designed to target specific neurocognitive deficits in geriatric depression with neuroplasticity‐based computerized cognitive remediation (NBCCR).

Immunity, Aging, and Geriatric Depression

Inflammatory processes are likely to play a causal role in geriatric depression. Geriatric depression occurs in the context of illnesses in which inflammatory processes are part of the pathogenesis. Both aging and depression are associated with immune responses, and the connectivity among mood-regulating structures may be modulated by inflammatory responses. Geriatric depression exacerbates the symptoms of comorbid disorders. Geriatric depression often occurs in persons exposed to chronic stress, a state precipitating geriatric depression and triggering proinflammatory responses. The successful treatment of comorbid conditions that increase central nervous system inflammatory responses has general health benefits and should be part of clinical practice.