Cancer- and treatment-related cognitive dysfunction (CRCD) is a common challenge faced by patients diagnosed with non-central nervous system (CNS) cancer. It has become increasingly recognized that ...multiple factors likely play a role in these symptoms, including the cancer disease process, systemic treatments (e.g., chemotherapy and endocrine therapies), and risk factors that may predispose an individual to both cancer and cognitive dysfunction. As the field has evolved, advanced neuroimaging techniques have been applied to better understand the neural correlates of CRCD. This review focuses on structural neuroimaging findings related to CRCD in adult non-CNS cancer populations, including examination of gray matter volume/density and white matter integrity differences between cancer patients and comparison groups, as well as emerging findings regarding structural network abnormalities. Overall, this literature has demonstrated consistent findings of reduced gray matter volume/density and white matter integrity in cancer patients relative to comparison groups. These are most prominent in individuals treated with chemotherapy, though alterations have also been noted in those treated with anti-estrogen and androgen-deprivation therapies. Alterations in gray and white matter structural network connectivity have also been identified. These structural abnormalities have been observed most prominently in frontal and temporal brain regions, and have been shown to correlate with subjective and objective cognitive function, as well as with physiological and clinical variables, helping to inform understanding of CRCD mechanisms. To date, however, structural neuroimaging techniques have not been utilized in systematic studies of potential CRCD treatments, suggesting a potentially fruitful avenue for future research.
Cancer- and treatment-related cognitive changes have been a focus of increasing research since the early 1980s, with meta-analyses demonstrating poorer performance in cancer patients in cognitive ...domains including executive functions, processing speed, and memory. To facilitate collaborative efforts, in 2011 the International Cognition and Cancer Task Force (ICCTF) published consensus recommendations for core neuropsychological tests for studies of cancer populations. Over the past decade, studies have used neuroimaging techniques, including structural and functional magnetic resonance imaging (fMRI) and positron emission tomography, to examine the underlying brain basis for cancer- and treatment-related cognitive declines. As yet, however, there have been no consensus recommendations to guide researchers new to this field or to promote the ability to combine data sets. We first discuss important methodological issues with regard to neuroimaging study design, scanner considerations, and sequence selection, focusing on concerns relevant to cancer populations. We propose a minimum recommended set of sequences, including a high-resolution T1-weighted volume and a resting state fMRI scan. Additional advanced imaging sequences are discussed for consideration when feasible, including task-based fMRI and diffusion tensor imaging. Important image data processing and analytic considerations are also reviewed. These recommendations are offered to facilitate increased use of neuroimaging in studies of cancer- and treatment-related cognitive dysfunction. They are not intended to discourage investigator-initiated efforts to develop cutting-edge techniques, which will be helpful in advancing the state of the knowledge. Use of common imaging protocols will facilitate multicenter and data-pooling initiatives, which are needed to address critical mechanistic research questions.
To prospectively examine alterations in working memory (WM) -associated brain activation related to breast cancer and treatment by using functional magnetic resonance imaging.
Patients treated with ...chemotherapy (CTx+; n = 16) or without chemotherapy (CTx-; n = 12) and healthy controls (n = 15) were scanned during an n-back task at baseline (after surgery but before radiation, chemotherapy, and/or antiestrogen treatment), 1 month after completion of chemotherapy (M1), and 1 year later (Y1), or at yoked intervals for CTx- and controls. SPM5 was used for all image analyses, which included cross-sectional between-group and group-by-time interaction and longitudinal within-group analyses, all using a statistical threshold of 0.001.
At baseline, patients with cancer showed increased bifrontal and decreased left parietal activation compared with controls. At M1, both cancer groups showed decreased frontal hyperactivation compared with controls, with increased hyperactivation at Y1. These cross-sectional findings were confirmed by group-by-time interaction analyses, which showed frontal activation decreases from baseline to M1 in patients compared with controls. Within-group analyses showed different patterns of longitudinal activation change by treatment group (CTx+ or CTx-), with prominent alterations in the frontal lobes bilaterally.
Significant frontal lobe hyperactivation to support WM was found in patients with breast cancer. Superimposed on this background, patients showed decreased frontal activation at M1, with partial return to the previously abnormal baseline at Y1. These functional changes correspond to frontal lobe regions where we previously reported structural changes in this cohort and provide prospective, longitudinal data that further elucidate mechanisms underlying cognitive effects related to breast cancer and its treatment.
To examine the impact of age and cognitive reserve on cognitive functioning in patients with breast cancer who are receiving adjuvant treatments.
Patients with breast cancer exposed to chemotherapy ...(n = 60; mean age, 51.7 years) were evaluated with a battery of neuropsychological and psychological tests before treatment and at 1, 6, and 18 months after treatment. Patients not exposed to chemotherapy (n = 72; mean age, 56.6 years) and healthy controls (n = 45; mean age, 52.9 years) were assessed at matched intervals.
Mixed-effects modeling revealed significant effects for the Processing Speed and Verbal Ability domains. For Processing Speed, a three-way interaction among treatment group, age, and baseline cognitive reserve (P < .001) revealed that older patients with lower baseline cognitive reserve who were exposed to chemotherapy had lower performance on Processing Speed compared with patients not exposed to chemotherapy (P = .003) and controls (P < .001). A significant group by time interaction for Verbal Ability (P = .01) suggested that the healthy controls and no chemotherapy groups improved over time. The chemotherapy group failed to improve at 1 month after treatment but improved during the last two follow-up assessments. Exploratory analyses suggested a negative effect of tamoxifen on Processing Speed (P = .036) and Verbal Memory (P = .05) in the no-chemotherapy group.
These data demonstrated that age and pretreatment cognitive reserve were related to post-treatment decline in Processing Speed in women exposed to chemotherapy and that chemotherapy had a short-term impact on Verbal Ability. Exploratory analysis of the impact of tamoxifen suggests that this pattern of results may be due to a combination of chemotherapy and tamoxifen.
Abstract The neurobiology of autism spectrum disorders (ASDs) has become increasingly understood since the advent of magnetic resonance imaging (MRI). Initial observations of an above-average head ...circumference were supported by structural MRI studies that found evidence of increased total brain volume and early rapid brain overgrowth in affected individuals. Subsequent research revealed consistent abnormalities in cortical gray and white matter volume in ASDs. The structural integrity and orientation of white matter have been further elucidated via diffusion tensor imaging methods. The emergence of functional MRI techniques led to an enhanced understanding of the neural circuitry of ASDs, demonstrating areas of dysfunctional cortical activation and atypical cortical specialization. These studies have provided evidence of underconnectivity in distributed cortical networks integral to the core impairments associated with ASDs. Abnormalities in the default-mode network during the resting state have also been identified. Overall, structural and functional MRI research has generated important insights into the neurobiology of ASDs. Additional research is needed to further delineate the underlying brain basis of this constellation of disorders.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a multi-center study assessing neuroimaging in diagnosis and longitudinal monitoring. Amnestic Mild Cognitive Impairment (MCI) often ...represents a prodromal form of dementia, conferring a 10-15% annual risk of converting to probable AD. We analyzed baseline 1.5T MRI scans in 693 participants from the ADNI cohort divided into four groups by baseline diagnosis and one year MCI to probable AD conversion status to identify neuroimaging phenotypes associated with MCI and AD and potential predictive markers of imminent conversion. MP-RAGE scans were analyzed using publicly available voxel-based morphometry (VBM) and automated parcellation methods. Measures included global and hippocampal grey matter (GM) density, hippocampal and amygdalar volumes, and cortical thickness values from entorhinal cortex and other temporal and parietal lobe regions. The overall pattern of structural MRI changes in MCI (n=339) and AD (n=148) compared to healthy controls (HC, n=206) was similar to prior findings in smaller samples. MCI-Converters (n=62) demonstrated a very similar pattern of atrophic changes to the AD group up to a year before meeting clinical criteria for AD. Finally, a comparison of effect sizes for contrasts between the MCI-Converters and MCI-Stable (n=277) groups on MRI metrics indicated that degree of neurodegeneration of medial temporal structures was the best antecedent MRI marker of imminent conversion, with decreased hippocampal volume (left > right) being the most robust. Validation of imaging biomarkers is important as they can help enrich clinical trials of disease modifying agents by identifying individuals at highest risk for progression to AD.
Adjuvant chemotherapy has been associated with mild cognitive decline among a subset of breast cancer survivors. Late cognitive effects after chemotherapy can have a deleterious impact on survivor ...quality of life and functional health; however, the etiology of chemotherapy-related cognitive dysfunction remains unknown.
We present a case of monozygotic twins who are discordant for breast cancer and chemotherapy exposure (ie, one twin contracted breast cancer and underwent chemotherapy, and the other had no breast cancer). As part of a larger study, each was evaluated with standardized, self-report measures of cognitive function, standard neuropsychological tests, and structural and functional magnetic resonance imaging (MRI).
Results indicated small differences in neuropsychological test performance but striking contrasts in self-reported cognitive complaints and structural and functional MRI images. Specifically, the twin who underwent chemotherapy had substantially more subjective cognitive complaints, more white matter hyperintensities on MRI, and an expanded spatial extent of brain activation during working memory processing than her nonaffected twin.
This case illustrates possible physiologic mechanisms that could produce long-term cognitive complaints among chemotherapy recipients and help formulate hypotheses for further empirical study in the area of chemotherapy-associated cognitive dysfunction.
PDF
