Prefrontal Cortex and Executive Function Impairments in Primary Breast Cancer

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Rd, MC5795, Stanford, CA 94305-5795, USA.
Archives of neurology (Impact Factor: 7.42). 11/2011; 68(11):1447-53. DOI: 10.1001/archneurol.2011.245
Source: PubMed


To examine differences in prefrontal-executive function between breast cancer (BC) survivors with and without a history of chemotherapy treatment compared with healthy control women and to determine the associations between prefrontal cortex deficits and behavioral impairments, as well as certain demographic and disease variables.
Observational study.
University-based research facility.
Twenty-five women with BC who had received chemotherapy, 19 women with BC who had not received chemotherapy, and 18 healthy female controls, all matched for age and other demographic variables.
Women with BC demonstrated significantly reduced activation in the left middle dorsolateral prefrontal cortex and premotor cortex compared with healthy controls. The chemotherapy group also demonstrated significantly reduced left caudal lateral prefrontal cortex activation and increased perseverative errors and reduced processing speed compared with the other 2 groups. Reduced left caudal lateral prefrontal cortex activation was significantly correlated with higher disease severity and elevated subjective executive dysfunction in the chemotherapy-treated women. Older age and lower educational level were associated with increased executive function impairment in the chemotherapy group.
These findings provide further evidence of neurological impairment associated with primary BC irrespective of treatment history. The left caudal lateral prefrontal region may be particularly vulnerable to the effects of chemotherapy and/or disease severity and may represent a novel biomarker of subjective executive dysfunction in chemotherapy-treated women. Furthermore, negative effects of chemotherapy on brain function may be exacerbated by such factors as increased age and lower educational level.

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Available from: Shelli R Kesler,
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    • "Importantly, global efficiency is associated with increased cognitive reserve in healthy adults (Fischer et al., 2014; Santarnecchi et al., 2014). Cognitive reserve refers to the brain's resilience to the clinical effects of aging, injury, and disease (Stern, 2012) and has been shown to moderate the cognitive effects of breast cancer (Ahles et al., 2010; Kesler et al., 2011). Local efficiency is the inverse of the average shortest path connecting all neighbors of a node, or in other words, the average efficiency of the local subgraphs or neighborhoods (Latora and Marchiori, 2001). "
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    ABSTRACT: Breast cancer and its treatments are associated with mild cognitive impairment and brain changes that could indicate an altered or accelerated brain aging process. We applied diffusion tensor imaging and graph theory to measure white matter organization and connectivity in 34 breast cancer survivors compared with 36 matched healthy female controls. We also investigated how brain networks (connectomes) in each group responded to simulated neurodegeneration based on network attack analysis. Compared with controls, the breast cancer group demonstrated significantly lower fractional anisotropy, altered small-world connectome properties, lower brain network tolerance to systematic region (node), and connection (edge) attacks and significant cognitive impairment. Lower tolerance to network attack was associated with cognitive impairment in the breast cancer group. These findings provide further evidence of diffuse white matter pathology after breast cancer and extend the literature in this area with unique data demonstrating increased vulnerability of the post-breast cancer brain network to future neurodegenerative processes. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neurobiology of aging 05/2015; 36:2429-2442. DOI:10.1016/j.neurobiolaging.2015.04.015 · 5.01 Impact Factor
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    • "First, participants of this study were a subset of participants from a larger neuropsychological study (Collins et al. 2013) that showed a dose-response decline of cognitive functioning. Secondly, previous studies have demonstrated grey matter loss in frontotemporal regions and functional studies (Ferguson et al. 2007; McDonald et al. 2012b; De Ruiter et al. 2011b; Kesler et al. 2011; Kesler et al. 2009; López Zunini et al. 2013) have shown abnormal activations in these areas during executive functioning and memory tasks. "
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    ABSTRACT: Purpose: Subsequent to chemotherapy treatment, breast cancer patients often report a decline in cognitive functioning that can adversely impact many aspects of their lives. Evidence has mounted in recent years indicating that a portion of breast cancer survivors who have undergone chemotherapy display reduced performance on objective measures of cognitive functioning relative to comparison groups. Neurophysiological support for chemotherapy-related cognitive impairment has been accumulating due to an increase in neuroimaging studies in this field; however, longitudinal studies are limited and have not examined the relationship between structural grey matter alterations and neuropsychological performance. The aim of this study was to extend the cancer-cognition literature by investigating the association between grey matter attenuation and objectively measured cognitive functioning in chemotherapy-treated breast cancer patients. Methods: Female breast cancer patients (n = 19) underwent magnetic resonance imaging after surgery but before commencing chemotherapy, one month following treatment, and one year after treatment completion. Individually matched controls (n = 19) underwent imaging at similar intervals. All participants underwent a comprehensive neuropsychological battery comprising four cognitive domains at these same time points. Longitudinal grey matter changes were investigated using voxel-based morphometry. Results: One month following chemotherapy, patients had distributed grey matter volume reductions. One year after treatment, a partial recovery was observed with alterations persisting predominantly in frontal and temporal regions. This course was not observed in the healthy comparison group. Processing speed followed a similar trajectory within the patient group, with poorest scores obtained one month following treatment and some improvement evident one year post-treatment. Conclusion: This study provides further credence to patient claims of altered cognitive functioning subsequent to chemotherapy treatment.
    SpringerPlus 08/2014; 3(1):444. DOI:10.1186/2193-1801-3-444
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    • "While chemotherapy is expected to induce a long-term risk of dementia syndrome, early troubles specific to some cognitive domains may be observed. In that respect, chemobrain refers to impairments of episodic memory, working memory, executive functions, attention and information processing speed [32] [33] [34], and recent neuroimaging studies revealed a fronto-subcortical effect of chemotherapy [35] [36] [37] [38]. In practice, patients experience difficulties regarding memory information retrieval and the memorization of information while processing. "
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    ABSTRACT: While chemotherapy is more commonly proposed to the elderly population with cancer, little is known about the impact of therapy on cognitive functions and the way of managing such dysfunctions in clinical practice among this population. Aging by itself is associated with cognitive modifications, comorbidities and functional decline, which may have a significant impact on the autonomy. In elderly patients with cancer, several factors like the biologic processes underlying the disease and therapies will contribute to favor the cognitive decline. The chemobrain phenomenon, referring to the chemotherapy-induced impairment of memory, executive function or information processing speed has been extensively described in patients with breast cancer, and the few studies available in older patients suggest that the impact could be more pronounced in patients with pre-existing troubles. Because cognitive dysfunction may impact the quality of life as well as compliance to treatment, assessing cognitive dysfunctions in the elderly cancer population is a challenge in clinical practice as it should influence the choice of the most appropriate therapy, including oral drugs. In that respect, geriatric assessment in oncology should include more sensitive screening tests than Mini Mental State Examination (MMSE) and if needed they have to be completed with a more detailed assessment of subtle disorders.
    Cancer Treatment Reviews 07/2014; 40(6). DOI:10.1016/j.ctrv.2014.03.003 · 7.59 Impact Factor
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