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Assessing brain volume changes in older women with breast cancer receiving adjuvant chemotherapy: a brain magnetic resonance imaging pilot study.

ABSTRACT: 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.

SUBMITTER: Chen BT

PROVIDER: S-EPMC5932862 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Assessing brain volume changes in older women with breast cancer receiving adjuvant chemotherapy: a brain magnetic resonance imaging pilot study.

Chen Bihong T BT Sethi Sean K SK Jin Taihao T Patel Sunita K SK Ye Ningrong N Sun Can-Lan CL Rockne Russell C RC Haacke E Mark EM 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

Breast cancer research : BCR 20180502 1

<h4>Background</h4>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.<h4>Methods</h4>Women a ...[more]

PMID: 29720224

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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:ImportanceCharacterizing longitudinal patterns of regional brain volume changes in a population with normal cognition at the individual level could improve understanding of the brain aging process and may aid in the prevention of age-related neurodegenerative diseases.ObjectiveTo investigate age-related trajectories of the volumes and volume change rates of brain structures in participants without dementia.Design, setting, and participantsThis cohort study was conducted from November 1, 2006, to April 30, 2021, at a single academic health-checkup center among 653 individuals who participated in a health screening program with more than 10 years of serial visits.ExposureSerial magnetic resonance imaging, Mini-Mental State Examination, health checkup.Main outcomes and measuresVolumes and volume change rates across brain tissue types and regions.ResultsThe study sample included 653 healthy control individuals (mean [SD] age at baseline, 55.1 [9.3] years; median age, 55 years [IQR, 47-62 years]; 447 men [69%]), who were followed up annually for up to 15 years (mean [SD], 11.5 [1.8] years; mean [SD] number of scans, 12.1 [1.9]; total visits, 7915). Each brain structure showed characteristic age-dependent volume and atrophy change rates. In particular, the cortical gray matter showed a consistent pattern of volume loss in each brain lobe with aging. The white matter showed an age-related decrease in volume and an accelerated atrophy rate (regression coefficient, -0.016 [95% CI, -0.012 to -0.011]; P < .001). An accelerated age-related volume increase in the cerebrospinal fluid-filled spaces, particularly in the inferior lateral ventricle and the Sylvian fissure, was also observed (ventricle regression coefficient, 0.042 [95% CI, 0.037-0.047]; P < .001; sulcus regression coefficient, 0.021 [95% CI, 0.018-0.023]; P < .001). The temporal lobe atrophy rate accelerated from approximately 70 years of age, preceded by acceleration of atrophy in the hippocampus and amygdala.Conclusions and relevanceIn this cohort study of adults without dementia, age-dependent brain structure volumes and volume change rates in various brain structures were characterized using serial magnetic resonance imaging scans. These findings clarified the normal distributions in the aging brain, which are essential for understanding the process of age-related neurodegenerative diseases.

Project description:ImportanceThe use of high-field magnetic resonance spectroscopy (MRS) in multiple brain regions of a large population of human participants facilitates in vivo study of localized or diffusely altered brain metabolites in patients with first-episode psychosis (FEP) compared to healthy participants.ObjectiveTo compare metabolite levels in 5 brain regions between patients with FEP (evaluated within 2 years of onset) and healthy controls, and to explore possible associations between targeted metabolite levels and neuropsychological test performance.Design, setting, and participantsCross-sectional design used 7-T MRS at a research MR imaging facility in participants recruited from clinics at the Johns Hopkins Schizophrenia Center and the local population. Eighty-one patients who had received a DSM-IV diagnosis of FEP within the last 2 years and 91 healthy age-matched (but not sex-matched) volunteers participated.Main outcomes and measuresBrain metabolite levels including glutamate, glutamine, γ-aminobutyric acid (GABA), N-acetylaspartate, N-acetylaspartyl glutamate, and glutathione, as well as performance on neuropsychological tests.ResultsThe mean (SD) age of 81 patients with FEP was 22.3 (4.4) years and 57 were male, while the mean (SD) age of 91 healthy participants was 23.3 (3.9) years and 42 were male. Compared with healthy participants, patients with FEP had lower levels of glutamate (F1,162 = 8.63, P = .02), N-acetylaspartate (F1,161 = 5.93, P = .03), GABA (F1,163 = 6.38, P = .03), and glutathione (F1,162 = 4.79, P = .04) in the anterior cingulate (all P values are corrected for multiple comparisons); lower levels of N-acetylaspartate in the orbitofrontal region (F1,136 = 7.23, P = .05) and thalamus (F1,133 = 6.78, P = .03); and lower levels of glutathione in the thalamus (F1,135 = 7.57, P = .03). Among patients with FEP, N-acetylaspartate levels in the centrum semiovale white matter were significantly correlated with performance on neuropsychological tests, including processing speed (r = 0.48; P < .001), visual (r = 0.33; P = .04) and working (r = 0.38; P = .01) memory, and overall cognitive performance (r = 0.38; P = .01).Conclusions and relevanceSeven-tesla MRS offers insights into biochemical changes associated with FEP and may be a useful tool for probing brain metabolism that ranges from neurotransmission to stress-associated pathways in participants with psychosis.

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Assessing brain volume changes in older women with breast cancer receiving adjuvant chemotherapy: a brain magnetic resonance imaging pilot study.

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Assessing brain volume changes in older women with breast cancer receiving adjuvant chemotherapy: a brain magnetic resonance imaging pilot study.

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