Neurodegenerative disease pathways are perturbed in patients with cancer who self-report cognitive changes and anxiety: A pathway impact analysis.

BACKGROUND: Cancer-related cognitive impairment (CRCI) and anxiety co-occur in patients with cancer. Little is known about mechanisms for the co-occurrence of these two symptoms. The purposes of this secondary analysis were to evaluate for perturbed pathways associated with the co-occurrence of self-reported CRCI and anxiety in patients with low versus high levels of these two symptoms and to identify potential mechanisms for the co-occurrence of CRCI and anxiety using biological processes common across any perturbed neurodegenerative disease pathways. METHODS: Patients completed the Attentional Function Index and the Spielberger State-Trait Anxiety Inventory six times over two cycles of chemotherapy. Based on findings from a previous latent profile analysis, patients were grouped into none versus both high levels of these symptoms. Gene expression was quantified, and pathway impact analyses were performed. Signaling pathways for evaluation were defined with the Kyoto Encyclopedia of Genes and Genomes database. RESULTS: A total of 451 patients had data available for analysis. Approximately 85.0% of patients were in the none class and 15.0% were in the both high class. Pathway impact analyses identified five perturbed pathways related to neurodegenerative diseases (i.e., amyotrophic lateral sclerosis, Huntington disease, Parkinson disease, prion disease, and pathways of neurodegeneration-multiple diseases). Apoptosis, mitochondrial dysfunction, oxidative stress, and endoplasmic reticulum stress were common biological processes across these pathways. CONCLUSIONS: This study is the first to describe perturbations in neurodegenerative disease pathways associated with CRCI and anxiety in patients receiving chemotherapy. These findings provide new insights into potential targets for the development of mechanistically based interventions.

Digital rhythm training improves reading fluency in children.

Musical instrument training has been linked to improved academic and cognitive abilities in children, but it remains unclear why this occurs. Moreover, access to instrument training is not always feasible, thereby leaving less fortunate children without opportunity to benefit from such training. Although music-based video games may be more accessible to a broader population, research is lacking regarding their benefits on academic and cognitive performance. To address this gap, we assessed a custom-designed, digital rhythm training game as a proxy for instrument training to evaluate its ability to engender benefits in math and reading abilities. Furthermore, we tested for changes in core cognitive functions related to math and reading to inform how rhythm training may facilitate improved academic abilities. Classrooms of 8-9 year old children were randomized to receive either 6 weeks of rhythm training (N = 32) or classroom instruction as usual (control; N = 21). Compared to the control group, results showed that rhythm training improved reading, but not math, fluency. Assessments of cognition showed that rhythm training also led to improved rhythmic timing and language-based executive function (Stroop task), but not sustained attention, inhibitory control, or working memory. Interestingly, only the improvements in rhythmic timing correlated with improvements in reading ability. Together, these results provide novel evidence that a digital platform may serve as a proxy for musical instrument training to facilitate reading fluency in children, and that such reading improvements are related to enhanced rhythmic timing ability and not other cognitive functions associated with reading performance. RESEARCH HIGHLIGHTS: Digital rhythm training in the classroom can improve reading fluency in 8-9 year old children Improvements in reading fluency were positively correlated with enhanced rhythmic timing ability Alterations in reading fluency were not predicted by changes in other executive functions that support reading A digital platform may be a convenient and cost-effective means to provide musical rhythm training, which in turn, can facilitate academic skills.

Quantifying attention span across the lifespan.

Introduction: Studies examining sustained attention abilities typically utilize metrics that quantify performance on vigilance tasks, such as response time and response time variability. However, approaches that assess the duration that an individual can maintain their attention over time are lacking. Methods: Here we developed an objective attention span metric that quantified the maximum amount of time that a participant continuously maintained an optimal "in the zone" sustained attention state while performing a continuous performance task. Results: In a population of 262 individuals aged 7-85, we showed that attention span was longer in young adults than in children and older adults. Furthermore, declines in attention span over time during task engagement were related to clinical symptoms of inattention in children. Discussion: These results suggest that quantifying attention span is a unique and meaningful method of assessing sustained attention across the lifespan and in populations with inattention symptoms.

Adverse Childhood Experiences and Higher Levels of Stress Are Associated With the Co-occurrence of Cancer-Related Cognitive Impairment and Anxiety.

OBJECTIVES: We sought to identify subgroups of patients with distinct joint cancer-related cognitive impairment (CRCI) AND anxiety profiles and evaluate for differences in demographic and clinical characteristics, as well as levels of global stress, cancer-specific stress, cumulative life stress, and resilience. DATA SOURCES: Patients (n = 1332) completed the Attentional Function Index and the Spielberger State Anxiety Inventory six times over two cycles of chemotherapy. Global, cancer-specific, and cumulative life stress and resilience were evaluated using Perceived Stress Scale, Impact of Event Scale-Revised, Life Stressor Checklist-Revised, and Connor-Davidson Resilience Scale, respectively. Latent profile analysis was used to identify subgroups of patients with distinct joint CRCI AND anxiety profiles. Differences were evaluated using parametric and nonparametric tests. RESULTS: Three classes were identified (ie, No CRCI and Low Anxiety [57.3%], Moderate CRCI and Moderate Anxiety [34.5%], and High CRCI and High Anxiety [8.2%]). All of the stress measures showed a dose-response effect (ie, as the CRCI AND anxiety profile worsened, scores for all three types of stress increased). The two highest symptom classes reported higher occurrence rates for six specific stressors (eg, emotional abuse, physical abuse, sexual harassment). CONCLUSIONS: Findings suggest that higher levels of co-occurring CRCI AND anxiety are associated with some common risk factors, as well as higher levels of stress and lower levels of resilience. Increased knowledge of modifiable risk factors and sources of stress associated with the co-occurrence of these two symptoms will assist clinicians to identify high-risk patients and implement individualized interventions.

The Multifactorial Model of Cancer-Related Cognitive Impairment.

PROBLEM IDENTIFICATION: Cancer-related cognitive impairment (CRCI) is common and is associated with cancer and its treatments. Evidence suggests that the causes are multifactorial, but the field is lacking a comprehensive conceptual model of CRCI to summarize existing knowledge and provide a way to understand and predict causal links, as well as to generate hypotheses. LITERATURE SEARCH: PubMed® and Google Scholar™ were searched, and 130 articles demonstrated several lacking factors needed for a more comprehensive CRCI model. DATA EVALUATION: The new multifactorial model of CRCI includes social determinants of health, patient-specific factors, co-occurring symptoms, treatment factors, and biologic mechanisms. SYNTHESIS: The multifactorial model of CRCI is based on established and emerging evidence. This model is inclusive of all cancer types and associated treatments. IMPLICATIONS FOR NURSING: Although it would be ideal to evaluate all the concepts and components in this model in a comprehensive fashion, investigators with existing datasets could evaluate portions of the model to determine directionality for some of the proposed relationships. The new model can be used to design preclinical and clinical studies of CRCI. Knowledge of the occurrence of CRCI and factors that contribute to this symptom will allow nurses to perform assessments of modifiable and nonmodifiable risk factors.

Acceptability of the LetSync App Wireframes for an mHealth Intervention to Improve HIV Care Engagement and Treatment Among Black Partnered Sexual Minority Men: Findings from In-Depth Qualitative Interviews.

BACKGROUND: HIV disparities continue to be a significant challenge affecting Black sexual minority men in the United States. Inadequate engagement and retention of patients in HIV care has been associated with poor health outcomes. Interventions to improve sustained commitment to HIV care are needed. Mobile health interventions can help facilitate access to and use of HIV health services, particularly among individuals at risk for disengaging with care. OBJECTIVE: We designed the LetSync app wireframes for a mobile health intervention using a couple-centered design approach to improve HIV engagement and treatment among Black sexual minority men and their partners. The objective of this study was to gauge future app user interest and elicit feedback to improve the design, development, and usability of the LetSync app. METHODS: We conducted in-depth interviews with 24 Black sexual minority men to assess the acceptability of the LetSync app wireframes between May 2020 and January 2021. Participants reviewed the LetSync app wireframes and provided feedback regarding perceived usefulness and interest in future app use and suggestions for improvement. RESULTS: Participants indicated interest in the future LetSync app and noted that the wireframes' features were acceptable and usable. In our study, the future LetSync app was frequently referred to as a potential resource that could help facilitate users' engagement in HIV care through the following mechanisms: enable scheduling of appointments and timely reminders for clinic visits; help improve HIV medication adherence; encourage and motivate participants to ask questions to their health care provider and stay engaged in conversations during clinic visits; facilitate effective communication by assisting couples with planning, coordination, and management of daily routines; help participants understand their partner's health needs, including access to and use of health care services; and facilitate participants' ability to improve their relationship skills, partner support, and self-efficacy in managing conflict. In addition to near-universal interest in potential daily app use, study participants indicted that they would recommend the LetSync app to other family members, friends, and people in their social networks who are living with HIV. CONCLUSIONS: Our findings revealed considerable interest in future app use for HIV care management, which could possibly increase the chance of the LetSync app being successfully adopted by Black sexual minority men in couples. Owing to its interactive and couple-centered approach, the LetSync app could help improve communication between Black sexual minority men and their partners and health providers. In addition, the LetSync app could provide an acceptable modality for these men to receive support in accessing HIV care services.

Better together: novel methods for measuring and modeling development of executive function diversity while accounting for unity.

Introduction: Executive functions (EFs) are linked to positive outcomes across the lifespan. Yet, methodological challenges have prevented precise understanding of the developmental trajectory of their organization. Methods: We introduce novel methods to address challenges for both measuring and modeling EFs using an accelerated longitudinal design with a large, diverse sample of students in middle childhood (N = 1,286; ages 8 to 14). We used eight adaptive assessments hypothesized to measure three EFs, working memory, context monitoring, and interference resolution. We deployed adaptive assessments to equate EF challenge across ages and a data-driven, network analytic approach to reveal the evolving diversity of EFs while simultaneously accounting for their unity. Results and discussion: Using this methodological paradigm shift brought new precision and clarity to the development of these EFs, showing these eight tasks are organized into three stable components by age 10, but refinement of composition of these components continues through at least age 14.

Influence of game features on attention in adults.

Introduction: The incorporation of game features into cognitive tasks can inform us about the influence of reward and motivation on attention. Continuous performance tasks (CPTs), designed to assess attention abilities, are examples of cognitive tasks that have been targeted for the addition of game features. However, previous results have been mixed regarding how game elements affect attention abilities and task performance. Methods: Here, we studied if there were factors that predict which individuals exhibit changes in attention from game features added to a CPT. Participants (N = 94, aged 21-71) played a traditional CPT and a game CPT with identical mechanics, but featured engaging game elements (aesthetics, storyline, competition, feedback, and reward). Results: We first found corroborating evidence that game features have mixed effects on attention performance: most attention metrics of interest exhibited no overall difference between the traditional and game CPT, while game elements reduced performance for a few metrics. Importantly, we also found that specific behavioral and demographic profiles predicted individual differences in performance on the game CPT compared to the traditional CPT. Those with more attention difficulties (ADHD symptoms), more reward responsiveness, and younger adults performed better on the game CPT while, conversely, those with fewer ADHD symptoms, less reward responsiveness, and older adults performed better on the traditional CPT. Discussion: These findings provide insights into how game features can influence attention in different individuals and have important implications for the use of game elements in cognitive tasks and training interventions.

An Evaluation of the Multifactorial Model of Cancer-Related Cognitive Impairment.

BACKGROUND: Up to 45% of patients report cancer-related cognitive impairment (CRCI). A variety of characteristics are associated with the occurrence and/or severity of CRCI. However, an important gap in knowledge of risk factors for CRCI is the relative contribution of each factor. The multifactorial model of cancer-related cognitive impairment (MMCRCI) is a conceptual model of CRCI that can be used to evaluate the strength of relationships between various factors and CRCI. OBJECTIVES: The purpose of this study was to use structural regression methods to evaluate the MMCRCI using data from a large sample of outpatients receiving chemotherapy ( n = 1,343). Specifically, the relationships between self-reported CRCI and four MMCRCI concepts (i.e., social determinants of health, patient-specific factors, treatment factors, and co-occurring symptoms) were examined. The goals were to determine how well the four concepts predicted CRCI and determine the relative contribution of each concept to deficits in perceived cognitive function. METHODS: This study is part of a larger, longitudinal study that evaluated the symptom experience of oncology outpatients receiving chemotherapy. Adult patients were diagnosed with breast, gastrointestinal, gynecological, or lung cancer; had received chemotherapy within the preceding 4 weeks; were scheduled to receive at least two additional cycles of chemotherapy; were able to read, write, and understand English; and gave written informed consent. Self-reported CRCI was assessed using the attentional function index. Available study data were used to define the latent variables. RESULTS: On average, patients were 57 years of age, college educated, and with a mean Karnofsky Performance Status score of 80. Of the four concepts evaluated, whereas co-occurring symptoms explained the largest amount of variance in CRCI, treatment factors explained the smallest amount of variance. A simultaneous structural regression model that estimated the joint effect of the four exogenous latent variables on the CRCI latent variable was not significant. DISCUSSION: These findings suggest that testing individual components of the MMCRCI may provide useful information on the relationships among various risk factors, as well as refinements of the model. In terms of risk factors for CRCI, co-occurring symptoms may be more significant than treatment factors, patient-specific factors, and/or social determinants of health in patients receiving chemotherapy.

A virtual reality program to assess cognitive function in multiple sclerosis: A pilot study.

Introduction: Cognitive impairment is a debilitating symptom in people with multiple sclerosis (MS). Most of the neuropsychological tasks have little resemblance to everyday life. There is a need for ecologically valid tools for assessing cognition in real-life functional contexts in MS. One potential solution would involve the use of virtual reality (VR) to exert finer control over the task presentation environment; however, VR studies in the MS population are scarce. Objectives: To explore the utility and feasibility of a VR program for cognitive assessment in MS. Methods: A VR classroom embedded with a continuous performance task (CPT) was assessed in 10 non-MS adults and 10 people with MS with low cognitive functioning. Participants performed the CPT with distractors (i.e., WD) and without distractors (i.e., ND). The Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT-II), and a feedback survey on the VR program was administered. Results: People with MS exhibited greater reaction time variability (RTV) compared to non-MS participants, and greater RTV in both WD and ND conditions was associated with lower SDMT. Conclusions: VR tools warrant further research to determine their value as an ecologically valid platform for assessing cognition and everyday functioning in people with MS.

Contribution of sustained attention abilities to real-world academic skills in children.

Sustained attention is a critical cognitive ability that improves over the course of development and predicts important real-world outcomes, such as academic achievement. However, the majority of work demonstrating links between sustained attention and academic skills has been conducted in lab-based settings that lack the ecological validity of a more naturalistic environment, like school. Further, most studies focus on targeted academic measures of specific sub-skills and have not fully examined whether this relationship generalizes to broad measures of academic achievement that are used for important, real-world, academic advancement decisions, such as standardized test scores. To address this gap, we examined the role of sustained attention in predicting targeted and broad assessments of academic abilities, where all skills were assessed in group-based environments in schools. In a sample of over 700 students aged 9-14, we showed that attention was positively related to performance on targeted assessments (math fluency and reading comprehension), as well as broad academic measures (statewide standardized test scores). Moreover, we found that attention was more predictive of targeted math sub-skills compared to assessments of broad math abilities, but was equally predictive of reading for both types of measures. Our findings add to our understanding of how sustained attention is linked to academic skills assessed in more 'real-world', naturalistic school environments and have important implications for designing tools to support student's academic success.

Blood-based biomarkers of cancer-related cognitive impairment in non-central nervous system cancer: A scoping review.

This scoping review was designed to synthesize the extant literature on associations between subjective and/or objective measures of cancer-related cognitive impairment (CRCI) and blood-based biomarkers in adults with non-central nervous system cancers. The literature search was done for studies published from the start of each database searched (i.e., MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, grey literature) through to October 20, 2021. A total of 95 studies are included in this review. Of note, a wide variety of biomarkers were evaluated. Most studies evaluated patients with breast cancer. A variety of cognitive assessment measures were used. The most consistent significant findings were with various subjective and objective measures of CRCI and levels of interleukin-6 and tumor necrosis factor. Overall, biomarker research is in an exploratory phase. However, this review synthesizes findings and proposes directions for future research.

Feasibility, engagement, and preliminary clinical outcomes of a digital biodata-driven intervention for anxiety and depression.

Hypothesis: The main hypothesis is that a digital, biodata-driven, and personalized program would exhibit high user retention and engagement, followed by more effective management of their depressive and anxiety symptoms. Objective: This pilot study explores the feasibility, acceptability, engagement, and potential impact on depressive and anxiety and quality of life outcomes of the 16-week Feel Program. Additionally, it examines potential correlations between engagement and impact on mental health outcomes. Methods: This single-arm study included 48 adult participants with mild or moderate depressive or anxiety symptoms who joined the 16-week Feel Program, a remote biodata-driven mental health support program created by Feel Therapeutics. The program uses a combination of evidence-based approaches and psychophysiological data. Candidates completed an online demographics and eligibility survey before enrolment. Depressive and anxiety symptoms were measured using the Patient Health Questionnaire and Generalized Anxiety Disorder Scale, respectively. The Satisfaction with Life Scale and the Life Satisfaction Questionnaire were used to assess quality of life. User feedback surveys were employed to evaluate user experience and acceptability. Results: In total, 31 participants completed the program with an overall retention rate of 65%. Completed participants spent 60 min in the app, completed 13 Mental Health Actions, including 5 Mental Health Exercises and 4.9 emotion logs on a weekly basis. On average, 96% of the completed participants were active and 76.8% of them were engaged with the sensor during the week. Sixty five percent of participants reported very or extremely high satisfaction, while 4 out of 5 were very likely to recommend the program to someone. Additionally, 93.5% of participants presented a decrease in at least one of the depressive or anxiety symptoms, with 51.6 and 45% of participants showing clinically significant improvement, respectively. Finally, our findings suggest increased symptom improvement for participants with higher engagement throughout the program. Conclusions: The findings suggest that the Feel Program may be feasible, acceptable, and valuable for adults with mild or moderate depressive and/or anxiety symptoms. However, controlled trials with bigger sample size, inclusion of a control group, and more diverse participant profiles are required in order to provide further evidence of clinical efficacy.

Real-world behavioral dataset from two fully remote smartphone-based randomized clinical trials for depression.

Most people with mental health disorders cannot receive timely and evidence-based care despite billions of dollars spent by healthcare systems. Researchers have been exploring using digital health technologies to measure behavior in real-world settings with mixed results. There is a need to create accessible and computable digital mental health datasets to advance inclusive and transparently validated research for creating robust real-world digital biomarkers of mental health. Here we share and describe one of the largest and most diverse real-world behavior datasets from over two thousand individuals across the US. The data were generated as part of the two NIMH-funded randomized clinical trials conducted to assess the effectiveness of delivering mental health care continuously remotely. The longitudinal dataset consists of self-assessment of mood, depression, anxiety, and passively gathered phone-based behavioral data streams in real-world settings. This dataset will provide a timely and long-term data resource to evaluate analytical approaches for developing digital behavioral markers and understand the effectiveness of mental health care delivered continuously and remotely.

Integrated cognitive and physical fitness training enhances attention abilities in older adults.

Preserving attention abilities is of great concern to older adults who are motivated to maintain their quality of life. Both cognitive and physical fitness interventions have been utilized in intervention studies to assess maintenance and enhancement of attention abilities in seniors, and a coupling of these approaches is a compelling strategy to buttress both cognitive and physical health in a time- and resource-effective manner. With this perspective, we created a closed-loop, motion-capture video game (Body-Brain Trainer: BBT) that adapts a player's cognitive and physical demands in an integrated approach, thus creating a personalized and cohesive experience across both domains. Older adults who engaged in two months of BBT improved on both physical fitness (measures of blood pressure and balance) and attention (behavioral and neural metrics of attention on a continuous performance task) outcome measures beyond that of an expectancy matched, active, placebo control group, with maintenance of improved attention performance evidenced 1 year later. Following training, the BBT group's improvement on the attention outcome measure exceeded performance levels attained by an untrained group of 20-year olds, and showed age-equilibration of a neural signature of attention shown to decline with age: midline frontal theta power. These findings highlight the potential benefits of an integrated, cognitive-physical, closed-loop training platform as a powerful tool for both cognitive and physical enhancement in older adults.

Leveraging technology to personalize cognitive enhancement methods in aging.

As population aging advances at an increasing rate, efforts to help people maintain or improve cognitive function late in life are critical. Although some studies have shown promise, the question of whether cognitive training is an effective tool for improving general cognitive ability remains incompletely explored, and study results to date have been inconsistent. Most approaches to cognitive enhancement in older adults have taken a 'one size fits all' tack, as opposed to tailoring interventions to the specific needs of individuals. In this Perspective, we argue that modern technology has the potential to enable large-scale trials of public health interventions to enhance cognition in older adults in a personalized manner. Technology-based cognitive interventions that rely on closed-loop systems can be tailored to individuals in real time and have the potential for global testing, extending their reach to large and diverse populations of older adults. We propose that the future of cognitive enhancement in older adults will rely on harnessing new technologies in scientifically informed ways.

Multimodal Biosensing for Vestibular Network-Based Cybersickness Detection.

Virtual reality (VR) has the potential to induce cybersickness (CS), which impedes CS-susceptible VR users from the benefit of emerging VR applications. To better detect CS, the current study investigated whether/how the newly proposed human vestibular network (HVN) is involved in flagship consumer VR-induced CS by simultaneously recording autonomic physiological signals as well as neural signals generated in sensorimotor and cognitive domains. The VR stimuli were made up of one or two moderate CS-inducing entertaining task(s) as well as a mild CS-inducing cognitive task implemented before and after the moderate CS task(s). Results not only showed that CS impaired cognitive control ability, represented by the degree of attentional engagement, but also revealed that combined indicators from all three HVN domains could together establish the best regression relationship with CS ratings. More importantly, we found that every HVN domain had its unique advantage with the dynamic changes in CS severity and time. These results provide evidence for involvement of the HVN in CS and indicate the necessity of HVN-based CS detection.

Assessing Cognitive Function in Multiple Sclerosis With Digital Tools: Observational Study.

BACKGROUND: Cognitive impairment (CI) is one of the most prevalent symptoms of multiple sclerosis (MS). However, it is difficult to include cognitive assessment as part of MS standard care since the comprehensive neuropsychological examinations are usually time-consuming and extensive. OBJECTIVE: To improve access to CI assessment, we evaluated the feasibility and potential assessment sensitivity of a tablet-based cognitive battery in patients with MS. METHODS: In total, 53 participants with MS (24 [45%] with CI and 29 [55%] without CI) and 24 non-MS participants were assessed with a tablet-based cognitive battery (Adaptive Cognitive Evaluation [ACE]) and standard cognitive measures, including the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT). Associations between performance in ACE and the SDMT/PASAT were explored, with group comparisons to evaluate whether ACE modules can capture group-level differences. RESULTS: Correlations between performance in ACE and the SDMT (R=-0.57, P<.001), as well as PASAT (R=-0.39, P=.01), were observed. Compared to non-MS and non-CI MS groups, the CI MS group showed a slower reaction time (CI MS vs non-MS: P<.001; CI MS vs non-CI MS: P=.004) and a higher attention cost (CI MS vs non-MS: P=.02; CI MS vs non-CI MS: P<.001). CONCLUSIONS: These results provide preliminary evidence that ACE, a tablet-based cognitive assessment battery, provides modules that could potentially serve as a digital cognitive assessment for people with MS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03569618; https://clinicaltrials.gov/ct2/show/NCT03569618.

Enhancing neural markers of attention in children with ADHD using a digital therapeutic.

Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition characterized by diminished attentional control. Critically, these difficulties are related to negative consequences in real-life functioning both during development and into adulthood. There is now growing evidence that modulating the underlying neural circuits related to attention can improve behavior and brain function in children with ADHD. We have previously shown that game-based digital therapeutics targeting a key neural marker of attention-midline frontal theta (MFT)-yield positive effects on attentional control in several populations. However, the effects of such digital therapeutics in children with ADHD and no other comorbidities has not been yet examined. To address this gap, we assessed a sample of 25 children with ADHD (8-12 years old) on neural, behavioral, and clinical metrics of attention before and after a 4-week at-home intervention on an iPad targeting MFT circuitry. We found that children showed enhancements on a neural measure of attention (MFT power), as well as on objective behavioral measures of attention and parent reports of clinical ADHD symptoms. Importantly, we observed relationships between the neural and behavioral cognitive improvements, demonstrating that those children who showed the largest intervention-related neural gains were also those that improved the most on the behavioral tasks indexing attention. These findings provide support for using targeted, digital therapeutics to enhance multiple features of attentional control in children with ADHD. Study registration: ClinicalTrials.gov registry (NCT03844269) https://clinicaltrials.gov/ct2/show/NCT03844269.

Cancer-related cognitive impairment is associated with perturbations in inflammatory pathways.

Cancer-related cognitive impairment (CRCI) is a significant problem for patients receiving chemotherapy. While a growing amount of pre-clinical and clinical evidence suggests that inflammatory mechanisms underlie CRCI, no clinical studies have evaluated for associations between CRCI and changes in gene expression. Therefore, the purpose of this study was to evaluate for differentially expressed genes and perturbed inflammatory pathways across two independent samples of patients with cancer who did and did not report CRCI. The Attentional Function Index (AFI) was the self-report measure used to assess CRCI. AFI scores of <5 and of >7.5 indicate low versus high levels of cognitive function, respectively. Of the 185 patients in Sample 1, 49.2% had an AFI score of <5 and 50.8% had an AFI score of >7.5. Of the 158 patients in Sample 2, 50.6% had an AFI score of <5 and 49.4% had an AFI score of >7.5. Data from 182 patients in Sample 1 were analyzed using RNA-seq. Data from 158 patients in Sample 2 were analyzed using microarray. Twelve KEGG signaling pathways were significantly perturbed between the AFI groups, five of which were signaling pathways related to inflammatory mechanisms (e.g., cytokine-cytokine receptor interaction, tumor necrosis factor signaling). This study is the first to describe perturbations in inflammatory pathways associated with CRCI. Findings highlight the role of cytokines both in terms of cytokine-specific pathways, as well as pathways involved in cytokine production and cytokine activation. These findings have the potential to identify new targets for therapeutics and lead to the development of interventions to improve cognition in patients with cancer.