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Subcortical brain iron deposition and cognitive performance in older women with breast cancer receiving adjuvant chemotherapy: A pilot MRI study.

ABSTRACT: As the number of older adults in the U.S. increases, so too will the incidence of cancer and cancer-related cognitive impairment (CRCI). However, the exact underlying biological mechanism for CRCI is not yet well understood. We utilized susceptibility-weighted imaging with quantitative susceptibility mapping, a non-invasive MRI-based technique, to assess longitudinal iron deposition in subcortical gray matter structures and evaluate its association with cognitive performance in women age 60+ with breast cancer receiving adjuvant chemotherapy and age-matched women without breast cancer as controls. Brain MRI scans and neurocognitive scores from the NIH Toolbox for Cognition were obtained before chemotherapy (time point 1) and within one month after the last infusion of chemotherapy for the patients and at matched intervals for the controls (time point 2). There were 14 patients age 60+ with breast cancer (mean age 66.3?±?5.3?years) and 13 controls (mean age 68.2?±?6.1?years) included in this study. Brain iron increased as age increased. There were no significant between- or within- group differences in neurocognitive scores or iron deposition at time point 1 or between time points 1 and 2 (p?>?0.01). However, there was a negative correlation between iron in the globus pallidus and the fluid cognition composite scores in the control group at time point 1 (r?=?-0.71; p?

SUBMITTER: Chen BT

PROVIDER: S-EPMC6298788 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Subcortical brain iron deposition and cognitive performance in older women with breast cancer receiving adjuvant chemotherapy: A pilot MRI study.

Chen Bihong T BT Ghassaban Kiarash K Jin Taihao T Patel Sunita K SK Ye Ningrong N Sun Can-Lan CL Kim Heeyoung H Rockne Russell C RC Mark Haacke E E Root James C JC Saykin Andrew J AJ Ahles Tim A TA Holodny Andrei I AI Prakash Neal N Mortimer Joanne J Waisman James J Yuan Yuan Y Somlo George G Li Daneng D Yang Richard R Tan Heidi H Katheria Vani V Morrison Rachel R Hurria Arti A

Magnetic resonance imaging 20180802

As the number of older adults in the U.S. increases, so too will the incidence of cancer and cancer-related cognitive impairment (CRCI). However, the exact underlying biological mechanism for CRCI is not yet well understood. We utilized susceptibility-weighted imaging with quantitative susceptibility mapping, a non-invasive MRI-based technique, to assess longitudinal iron deposition in subcortical gray matter structures and evaluate its association with cognitive performance in women age 60+ wit ...[more]

PMID: 30076946

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Project description:BACKGROUND:Cognitive decline is among the most feared treatment-related outcomes of older adults with cancer. The majority of older patients with breast cancer self-report cognitive problems during and after chemotherapy. Prior neuroimaging research has been performed mostly in younger patients with cancer. The purpose of this study was to evaluate longitudinal changes in brain volumes and cognition in older women with breast cancer receiving adjuvant chemotherapy. METHODS:Women aged ??60 years with stage I-III breast cancer receiving adjuvant chemotherapy and age-matched and sex-matched healthy controls were enrolled. All participants underwent neuropsychological testing with the US National Institutes of Health (NIH) Toolbox for Cognition and brain magnetic resonance imaging (MRI) prior to chemotherapy, and again around one month after the last infusion of chemotherapy. Brain volumes were measured using Neuroreader™ software. Longitudinal changes in brain volumes and neuropsychological scores were analyzed utilizing linear mixed models. RESULTS:A total of 16 patients with breast cancer (mean age 67.0, SD 5.39 years) and 14 age-matched and sex-matched healthy controls (mean age 67.8, SD 5.24 years) were included: 7 patients received docetaxel and cyclophosphamide (TC) and 9 received chemotherapy regimens other than TC (non-TC). There were no significant differences in segmented brain volumes between the healthy control group and the chemotherapy group pre-chemotherapy (p?>?0.05). Exploratory hypothesis generating analyses focusing on the effect of the chemotherapy regimen demonstrated that the TC group had greater volume reduction in the temporal lobe (change?=?-?0.26) compared to the non-TC group (change?=?0.04, p for interaction?=?0.02) and healthy controls (change?=?0.08, p for interaction?=?0.004). Similarly, the TC group had a decrease in oral reading recognition scores (change?=?-?6.94) compared to the non-TC group (change?=?-?1.21, p for interaction?=?0.07) and healthy controls (change?=?0.09, p for interaction?=?0.02). CONCLUSIONS:There were no significant differences in segmented brain volumes between the healthy control group and the chemotherapy group; however, exploratory analyses demonstrated a reduction in both temporal lobe volume and oral reading recognition scores among patients on the TC regimen. These results suggest that different chemotherapy regimens may have differential effects on brain volume and cognition. Future, larger studies focusing on older adults with cancer on different treatment regimens are needed to confirm these findings. TRIAL REGISTRATION:ClinicalTrials.gov, NCT01992432 . Registered on 25 November 2013. Retrospectively registered.

Project description:PurposeOlder cancer patients are at increased risk of cancer-related cognitive impairment. The purpose of this study was to assess the alterations in intrinsic brain activity associated with adjuvant chemotherapy in older women with breast cancer.MethodsChemotherapy treatment (CT) group included sixteen women aged ≥ 60 years (range 60-82 years) with stage I-III breast cancers, who underwent both resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological testing with NIH Toolbox for Cognition before adjuvant chemotherapy, at time point 1 (TP1), and again within 1 month after completing chemotherapy, at time point 2 (TP2). Fourteen age- and sex-matched healthy controls (HC) underwent the same assessments at matched intervals. Three voxel-wise rs-fMRI parameters: amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity, were computed at each time point. The changes in rs-fMRI parameters from TP1 to TP2 for each group, the group differences in changes (the CT group vs. the HC group), and the group difference in the baseline rs-fMRI parameters were assessed. In addition, correlative analysis between the rs-fMRI parameters and neuropsychological testing scores was also performed.ResultsIn the CT group, one brain region, which included parts of the bilateral subcallosal gyri and right anterior cingulate gyrus, displayed increased ALFF from TP1 to TP2 (cluster p-corrected = 0.024); another brain region in the left precuneus displayed decreased fALFF from TP1 to TP2 (cluster level p-corrected = 0.025). No significant changes in the rs-fMRI parameters from TP1 to TP2 were observed in the HC group. Although ALFF and fALFF alterations were observed only in the CT group, none of the between-group differences in rs-fMRI parameter changes reached statistical significance.ConclusionsOur study results of ALFF and fALFF alterations in the chemotherapy-treated women suggest that adjuvant chemotherapy may affect intrinsic brain activity in older women with breast cancer.

Project description:Background: Subcortical vascular cognitive impairment (sVCI), caused by cerebral small vessel disease, accounts for the majority of vascular cognitive impairment, and is characterized by an insidious onset and impaired memory and executive function. If not recognized early, it inevitably develops into vascular dementia. Several quantitative studies have reported the consistent results of brain regions in sVCI patients that can be used to predict dementia conversion. The purpose of the study was to explore the exact abnormalities within the brain in sVCI patients by combining the coordinates reported in previous studies. Methods: The PubMed, Embase, and Web of Science databases were thoroughly searched to obtain neuroimaging articles on the amplitude of low-frequency fluctuation, regional homogeneity, and functional connectivity in sVCI patients. According to the activation likelihood estimation (ALE) algorithm, a meta-analysis based on coordinate and functional connectivity modeling was conducted. Results: The quantitative meta-analysis included 20 functional imaging studies on sVCI patients. Alterations in specific brain regions were mainly concentrated in the frontal lobes including the middle frontal gyrus, superior frontal gyrus, medial frontal gyrus, and precentral gyrus; parietal lobes including the precuneus, angular gyrus, postcentral gyrus, and inferior parietal lobule; occipital lobes including the lingual gyrus and cuneus; temporal lobes including the fusiform gyrus and middle temporal gyrus; and the limbic system including the cingulate gyrus. These specific brain regions belonged to important networks known as the default mode network, the executive control network, and the visual network. Conclusion: The present study determined specific abnormal brain regions in sVCI patients, and these brain regions with specific changes were found to belong to important brain functional networks. The findings objectively present the exact abnormalities within the brain, which help further understand the pathogenesis of sVCI and identify them as potential imaging biomarkers. The results may also provide a basis for new approaches to treatment.

Dataset Information

Subcortical brain iron deposition and cognitive performance in older women with breast cancer receiving adjuvant chemotherapy: A pilot MRI study.

Publications

Subcortical brain iron deposition and cognitive performance in older women with breast cancer receiving adjuvant chemotherapy: A pilot MRI study.

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