The Developmental Trajectory of Cancer-Related Cognitive Impairment in Breast Cancer Patients: A Systematic Review of Longitudinal Neuroimaging Studies

Abstract

This systematic review explored the neurobiological mechanisms underlying the clinical time course of cancer-related cognitive impairment (CRCI) in breast cancer patients through the review of longitudinal neuroimaging studies. Before chemotherapy, results reported no evidence for neuropsychological, structural (gray matter) and brain perfusion changes. However, functional brain alterations were evident and revealed a frontoparietal hyperactivation during working memory tasks. Fatigue and number of days since surgery were the two suggested confounding factors. Acutely after chemotherapy, this review found no evidence for neuropsychological changes while suggesting a pattern of frontal structural, perfusion and functional brain abnormalities. These findings seemed to be dependent on age, menopausal status at baseline, and fMRI task performed. Years after chemotherapy, results revealed evidence of partial neuropsychological, structural, and functional brain recovery. Regarding brain abnormality, this review suggested that it may begin quite early in the disease course, be more prominent shortly after chemotherapy and partially recover over time. Several hypotheses underlying these changes were discussed. The present review also provided important information for developing a time-specific treatment and prevention strategies and for the consideration of functional neuroimaging as a relevant tool for CRCI diagnosis, clinical monitoring, and intervention studies. The findings also suggested the need to implement studies with longitudinal designs, including a pre-treatment assessment, since cross-sectional studies were not able to detect this pattern of recovery over time, supporting only the theory of brain abnormalities, in breast cancer survivors.

A systematic review on the use of quantitative imaging to detect cancer therapy adverse effects in normal-appearing brain tissue

“…Similar findings after CTx in acute lymphoblastic leukemia [14], and after RTx in CNS tumors [15] are also reported. Since diffusion tensor imaging (DTI) and functional MRI (fMRI) have been used clinically in the context of brain surgery-mapping the networks that need to be kept intact-these sequences have also been reviewed several times for their ability to pick up treatment-induced brain changes [11,13,14,16,17].…”

“…Structural changes in white matter (WM), measured with diffusion tensor imaging, have also shown a decrease in fractional anisotropy, potentially reflecting a decrease in fiber density and myelin content, after CTx in breast cancer, associated with cognitive decline [13]. Similar findings after CTx in acute lymphoblastic leukemia [14], and after RTx in CNS tumors [15] are also reported. Since diffusion tensor imaging (DTI) and functional MRI (fMRI) have been used clinically in the context of brain surgery-mapping the networks that need to be kept intact-these sequences have also been reviewed several times for their ability to pick up treatment-induced brain changes [11,13,14,16,17].…”

Cross-Sectional Characterization of Local Brain Network Connectivity Pre and Post Breast Cancer Treatment and Distinct Association With Subjective Cognitive and Psychological Function

“…Left middle and left superior frontal connections with left Rolandic operculum, left superior occipital, right superior temporal and right middle temporal regions likely involve attention and executive function integration with verbal memory, selective visual attention and somatosensory processing (59). Taken together, these findings may reflect the deficits in verbal memory, verbal fluency, attention, executive function and emotion regulation that are frequently observed among breast cancer patients and survivors (60)(61)(62).…”

Blood and neuroimaging biomarkers of cognitive sequelae in breast cancer patients throughout chemotherapy: A systematic review

“…Cancer-related cognitive impairment (CRCI) is broadly reported, with a wide range (17–78%) of patients being affected, mainly in domains of memory, attention, psychomotor speed and executive functioning. CRCI can emerge before the start of therapy, during therapy and persist up to years after treatment (see recent reviews [2] , [3] , [4] ).…”

“…In addition to the acquisition of neuroimaging, blood-based biomarkers provide a more affordable and easily accessible approach in identifying cancer patients who are possibly more susceptible for cognitive decline throughout time. Increased peripheral inflammation, hormonal deregulation, anemia, changes in epigenetic markers or telomeric length have all been observed after treatment with chemotherapy [ 1 , 3 ]. An overview of associations/correlations between cognitive impairments and specific circulating factors, cerebral spinal fluid constituents, and genetic polymorphisms in diverse cancer populations was provided by Castel and colleagues [9] .…”