IntroductionSeveral previous studies have demonstrated that cancer chemotherapy is associated with brain injury and cognitive dysfunction. However, evidence suggests that cancer pathogenesis alone may play a role, even in non‐CNS cancers.MethodsUsing a multimodal neuroimaging approach, we measured structural and functional connectome topology as well as functional network dynamics in newly diagnosed patients with breast cancer. Our study involved a novel, pretreatment assessment that occurred prior to the initiation of any cancer therapies, including surgery with anesthesia. We enrolled 74 patients with breast cancer age 29–65 and 50 frequency‐matched healthy female controls who underwent anatomic and resting‐state functional MRI as well as cognitive testing.ResultsCompared to controls, patients with breast cancer demonstrated significantly lower functional network dynamics (p = .046) and cognitive functioning (p < .02, corrected). The breast cancer group also showed subtle alterations in structural local clustering and functional local clustering (p < .05, uncorrected) as well as significantly increased correlation between structural global clustering and functional global clustering compared to controls (p = .03). This hyper‐correlation between structural and functional topologies was significantly associated with cognitive dysfunction (p = .005).ConclusionsOur findings could not be accounted for by psychological distress and suggest that non‐CNS cancer may directly and/or indirectly affect the brain via mechanisms such as tumor‐induced neurogenesis, inflammation, and/or vascular changes, for example. Our results also have broader implications concerning the importance of the balance between structural and functional connectome properties as a potential biomarker of general neurologic deficit.

ImportancePrevious studies of post-acute COVID-19 syndrome have focused on critical cases with severe disease. However, most cases are mild to moderate in disease severity.ObjectiveWe aimed to examine cognitive outcomes in cases of non-critical, mild-to-moderate COVID-19. Design, Setting, and Participants: In this cross-sectional study, we enrolled 72 adults aged 22 to 65 years in Central Texas who had non-critical, mild-to-moderate COVID-19 infection between 13 January 2021 and 20 April 2021.Main Outcomes and MeasuresWe remotely administered cognitive-behavioral testing to determine the frequency of cognitive impairment and examine demographic, clinical, and psychosocial contributors to impairment.ResultsThe frequency of objective cognitive impairment was 40%. The largest number of participants (24%) showed impairment on a measure of executive functioning. Attention and processing speed was more impaired in males (OR = 1.5, 95%CI = 0.23–2.9). Males endorsed lower adherence to social distancing guidelines (U = 590, p = 0.01), which was in turn associated with cognitive impairment across participants (r = −0.30, p = 0.01). Younger age was correlated with impairment (r = −0.26, p = 0.03) but was also associated with racial/ethnic minority status (r = −0.31, p = 0.01) and increased psychological symptoms (p &lt; 0.04). Greater number of COVID-19 symptoms was correlated with lower subjective cognitive function (r = −0.38, p = 0.001) as well as psychosocial function (r &gt; 0.24, p &lt; 0.05). Moderate COVID-19 severity was associated with attention/processing speed impairment (r = 0.27, p = 0.03), increased pain (r = 0.31, p = 0.01), and higher number of COVID-19 symptoms (r = 0.32, p = 0.01).Conclusion and RelevanceMild or moderate COVID-19 infection may be associated with cognitive impairments, especially in the domain of executive functioning. A subgroup of younger individuals may be more vulnerable to cognitive and psychosocial effects of COVID-19.HighlightsQuestion: How frequent is cognitive impairment among non-critical, mild-to-moderate COVID-19 survivors?FindingsIn this cross-sectional study of 72 adults, 40% demonstrated cognitive impairment, particularly in executive function.MeaningNeurologic sequelae, such as cognitive impairment, may be common following COVID-19 infection.

Interventions targeting stress, loneliness, and sleep quality may improve perceived cognitive functioning in breast cancer survivors.

Cancer and its treatments are associated with increased risk for cancer-related cognitive impairment (CRCI). Methods and measures used to study and assess self-reported CRCI (sr-CRCI), however, remain diverse, resulting in heterogeneity across studies. The Patient-Reported Outcomes Working Group has been formed to promote homogeneity in the methods used to study sr-CRCI. In this report, using a psychometric taxonomy, we inventory and appraise instruments used in research to measure sr-CRCI, and we consider advances in patient-reported outcome methodology. Given its psychometric properties, we recommend the Patient-Reported Outcome Measurement Information System Cognitive Function Short Form 8a for measurement of sr-CRCI in cancer patients and survivors, at a minimum, in order to increase scientific rigor and progress in addressing CRCI.

Many women unfortunately experience CRCI after breast cancer chemotherapy, with limited treatment options available to improve cognitive function. This review synthesizes current evidence to support the associations between modifiable factors and CRCI and can inform research to evaluate these factors prospectively. The clinical implications of these findings suggest that lifestyle factors such as physical activity, stress management, and sleep quality may be appropriate targets for behavioral interventions to improve cognitive function following breast cancer chemotherapy; however, further research is necessary.