Establishing construct validity of neuropsychological tests in cancer survivors.

OBJECTIVE: Cancer-related cognitive impairments (CRCI) are frequently reported among cancer survivors, and attention is the most frequently assessed cognitive domain in CRCI. However, there is no consensus as to whether attention is impaired. We suggest that a major reason for this lack of agreement is a lack of construct validity for neuropsychological attention tests. We propose to assess the construct validity of neuropsychological attention tests with respect to experimental paradigms from cognitive psychology. METHODS: Self-reported cancer survivors (N = 314) completed an online battery comprising six experimental attention paradigms and eight neuropsychological tests. Confirmatory factor analysis was used to evaluate the fit of five models derived from a general population sample (N = 636) in a previous study (M. Treviño, Cogn Res Princ Implic, in press). We then subjected the best-fitting model to a measurement invariance analysis. RESULTS: The best-fitting model was a six intercorrelated factor structure, comprising Capacity, Search, Digit Span, Arithmetic, Sustained Attention, and Flanker Interference factors. Configural and weak invariance held, indicating that the factor loadings were invariant across groups. Strong invariance, indicating that intercepts were also invariant, held except for the Approximate Number Sense test. CONCLUSIONS: According to our factor model, Spatial Span and Digit Symbol Coding measure attentional capacity, while the Trail Making Test (A&B) and Letter Cancellation tests measure visual search ability. However, Digit Span and Arithmetic tests do not measure attention. We hope that these results will lead to better scientific models, better patient education, and, ultimately, improved outcomes for survivors.

The role of intraindividual cognitive variability in posttraumatic stress syndromes and cognitive aging: a literature search and proposed research agenda.

OBJECTIVES: Cognitive impairments are directly related to severity of symptoms and are a primary cause for functional impairment. Intraindividual cognitive variability likely plays a role in both risk and resiliency from symptoms. In fact, such cognitive variability may be an earlier marker of cognitive decline and emergent psychiatric symptoms than traditional psychiatric or behavioral symptoms. Here, our objectives were to survey the literature linking intraindividual cognitive variability, trauma, and dementia and to suggest a potential research agenda. DESIGN: A wide body of literature suggests that exposure to major stressors is associated with poorer cognitive performance, with intraindividual cognitive variability in particular linked to the development of posttraumatic stress disorder (PTSD) in the aftermath of severe trauma. MEASUREMENTS: In this narrative review, we survey the empirical studies to date that evaluate the connection between intraindividual cognitive variability, PTSD, and pathological aging including dementia. RESULTS: The literature suggests that reaction time (RT) variability within an individual may predict future cognitive impairment, including premature cognitive aging, and is significantly associated with PTSD symptoms. CONCLUSIONS: Based on our findings, we argue that intraindividual RT variability may serve as a common pathological indicator for trauma-related dementia risk and should be investigated in future studies.

Cognitive test scores vary with choice of personal digital device.

Mobile- and web-based psychological research are a valuable addition to the set of tools available for scientific study, reducing logistical barriers for research participation and allowing the recruitment of larger and more diverse participant groups. However, this comes at the cost of reduced control over the technology used by participants, which can introduce new sources of variability into study results. In this study, we examined differences in measured performance on timed and untimed cognitive tests between users of common digital devices in 59,587 (Study 1) and 3818 (Study 2) visitors to TestMyBrain.org , a web-based cognitive testing platform. Controlling for age, gender, educational background, and cognitive performance on an untimed vocabulary test, users of mobile devices, particularly Android smartphones, showed significantly slower performance on tests of reaction time than users of laptop and desktop computers, suggesting that differences in device latency affect measured reaction times. Users of devices that differ in user interface (e.g. screen size, mouse vs. touchscreen) also show significant differences (p < 0.001) in measured performance on tests requiring fast reactions or fine motor movements. By quantifying the contribution of device differences to measured cognitive performance in an online setting, we hope to improve the accuracy of mobile- and web-based cognitive assessments, allowing these methods to be used more effectively.

Use of Geosocial Networking Applications Is Associated With Compulsive Sexual Behavior Disorder in an Online Sample.

BACKGROUND: Geosocial networking applications (GNAs) are relatively new outlets through which individuals may find partners for sexual encounters. There has been a paucity of research on the associations between use of these platforms and measures of mental health and compulsive sexual behavior disorder (CSBD). AIM: To examine associations between use of GNA, anxiety, and CSBD. METHODS: Using data from a large nontargeted Web-based sample (N = 4,203), we examined demographics associated with the use of GNAs. Using multivariable logistic regression adjusting for demographic differences between users and non-users, we examined associations between GNA use, anxiety, and CSBD. OUTCOMES: The outcomes are Generalized Anxiety Disorder-7 and a modified Hypersexual Behavior Inventory-19. RESULTS: The percentage of participants that reported they used GNAs was 12.3%. Those who reported using the applications compared with those who did not were more likely to be young, male, and nonheterosexual. After adjusting for demographic variables, GNAs use was associated with CSBD (adjusted odds ratio = 1.62, 95% confidence interval: 1.09-2.37, P = .015) but not anxiety. CLINICAL IMPLICATIONS: This study is an initial foray into the relationships between GNA and mental health, establishing a relationship between GNA use and CSBD. Future research is needed to better understand the relationships between GNA use, psychopathology, and CSBD. STRENGTHS & LIMITATIONS: Strengths of the study include its large sample size and nontargeted recruitment design, which minimizes confirmation bias. Limitations include the cross-sectional nature of this study, which precludes determination of the direction of causation. CONCLUSION: Use of GNAs was prevalent among our sample and associated with CSBD. GNA use may represent an important platform through which CSBD manifests. Conversely, GNA use may drive CSBD. Turban JL, Passell E, Scheuer L, et al. Use of Geosocial Networking Applications Is Associated With Compulsive Sexual Behavior Disorder in an Online Sample. J Sex Med 2020;17:1574-1578.

Emerging SARS-CoV-2 Resistance After Antiviral Treatment.

Importance: Previous studies have identified mutations in SARS-CoV-2 strains that confer resistance to nirmatrelvir, yet how often this resistance arises and its association with posttreatment virologic rebound is not well understood. Objective: To examine the prevalence of emergent antiviral resistance after nirmatrelvir treatment and its association with virologic rebound. Design, Setting, and Participants: This cohort study enrolled outpatient adults with acute COVID-19 infection from May 2021 to October 2023. Participants were divided into those who received antiviral therapy and those who did not. The study was conducted at a multicenter health care system in Boston, Massachusetts. Exposure: Treatment regimen, including none, nirmatrelvir, and remdesivir. Main Outcomes and Measures: The primary outcome was emergent SARS-CoV-2 antiviral resistance, defined as the detection of antiviral resistance mutations, which were not present at baseline, were previously associated with decreased antiviral efficacy, and emerged during or after completion of a participant's treatment. Next-generation sequencing was used to detect low frequency mutations down to 1% of the total viral population. Results: Overall, 156 participants (114 female [73.1%]; median [IQR] age, 56 [38-69] years) were included. Compared with 63 untreated individuals, the 79 who received nirmatrelvir were older and more commonly immunosuppressed. After sequencing viral RNA from participants' anterior nasal swabs, nirmatrelvir resistance mutations were detected in 9 individuals who received nirmatrelvir (11.4%) compared with 2 of those who did not (3.2%) (P = .09). Among the individuals treated with nirmatrelvir, those who were immunosuppressed had the highest frequency of resistance emergence (5 of 22 [22.7%]), significantly greater than untreated individuals (2 of 63 [3.1%]) (P = .01). Similar rates of nirmatrelvir resistance were found in those who had virologic rebound (3 of 23 [13.0%]) vs those who did not (6 of 56 [10.7%]) (P = .86). Most of these mutations (10 of 11 [90.9%]) were detected at low frequencies (<20% of viral population) and reverted to the wild type at subsequent time points. Emerging remdesivir resistance mutations were only detected in immunosuppressed individuals (2 of 14 [14.3%]) but were similarly low frequency and transient. Global Initiative on Sharing All Influenza Data analysis showed no evidence of increased nirmatrelvir resistance in the United States after the authorization of nirmatrelvir. Conclusions and Relevance: In this cohort study of 156 participants, treatment-emergent nirmatrelvir resistance mutations were commonly detected, especially in individuals who were immunosuppressed. However, these mutations were generally present at low frequencies and were transient in nature, suggesting a low risk for the spread of nirmatrelvir resistance in the community with the current variants and drug usage patterns.

Association of Retrospectively Reported Concussion Symptoms with Objective Cognitive Performance in Former American-Style Football Players.

OBJECTIVE: Sustaining concussions has been linked to health issues later in life, yet evidence for associations between contact sports exposure and long-term cognitive performance is mixed. This cross-sectional study of former professional American-style football players tested the association of several measures of football exposure with later life cognitive performance, while also comparing the cognitive performance of former players to nonplayers. METHODS: In total, 353 former professional football players (Mage = 54.3) completed both (1) an online cognitive test battery measuring objective cognitive performance and (2) a survey querying demographic information, current health conditions, and measures of past football exposure, including recollected concussion symptoms playing professional football, diagnosed concussions, years of professional play, and age of first football exposure. Testing occurred an average of 29 years after former players' final season of professional play. In addition, a comparison sample of 5,086 male participants (nonplayers) completed one or more cognitive tests. RESULTS: Former players' cognitive performance was associated with retrospectively reported football concussion symptoms (rp = -0.19, 95% CI -0.09 to -0.29; p < 0.001), but not with diagnosed concussions, years of professional play, or age of first football exposure. This association could be due to differences in pre-concussion cognitive functioning, however, which could not be estimated based on available data. CONCLUSIONS: Future investigations of the long-term outcomes of contact sports exposure should include measures of sports-related concussion symptoms, which were more sensitive to objective cognitive performance than other football exposure measures, including self-reported diagnosed concussions.

Accurate Prediction of Momentary Cognition From Intensive Longitudinal Data.

BACKGROUND: Deficits in cognitive performance are implicated in the development and maintenance of psychopathology. Emerging evidence further suggests that within-person fluctuations in cognitive performance may represent sensitive early markers of neuropsychiatric decline. Incorporating routine cognitive assessments into standard clinical care-to identify between-person differences and monitor within-person fluctuations-has the potential to improve diagnostic screening and treatment planning. In support of these goals, it is critical to understand to what extent cognitive performance varies under routine, remote assessment conditions (i.e., momentary cognition) in relation to a wide range of possible predictors. METHODS: Using data-driven, high-dimensional methods, we ranked strong predictors of momentary cognition and evaluated out-of-sample predictive accuracy. Our approach leveraged innovations in digital technology, including ambulatory assessment of cognition and behavior 1) at scale (n = 122 participants, n = 94 females), 2) in naturalistic environments, and 3) within an intensive longitudinal study design (mean = 25.5 assessments/participant). RESULTS: Reaction time (R2 > 0.70) and accuracy (0.56 >R2 > 0.35) were strongly predicted by age, between-person differences in mean performance, and time of day. Effects of self-reported, intraindividual fluctuations in environmental (e.g., noise) and internal (e.g., stress) states were also observed. CONCLUSIONS: Our results provide robust estimates of effect size to characterize sources of cognitive variability, to support the identification of optimal windows for psychosocial interventions, and to possibly inform clinical evaluation under remote neuropsychological assessment conditions.

Glycemic Variability and Fluctuations in Cognitive Status in Adults With Type 1 Diabetes (GluCog): Observational Study Using Ecological Momentary Assessment of Cognition.

BACKGROUND: Individuals with type 1 diabetes represent a population with important vulnerabilities to dynamic physiological, behavioral, and psychological interactions, as well as cognitive processes. Ecological momentary assessment (EMA), a methodological approach used to study intraindividual variation over time, has only recently been used to deliver cognitive assessments in daily life, and many methodological questions remain. The Glycemic Variability and Fluctuations in Cognitive Status in Adults with Type 1 Diabetes (GluCog) study uses EMA to deliver cognitive and self-report measures while simultaneously collecting passive interstitial glucose in adults with type 1 diabetes. OBJECTIVE: We aimed to report the results of an EMA optimization pilot and how these data were used to refine the study design of the GluCog study. An optimization pilot was designed to determine whether low-frequency EMA (3 EMAs per day) over more days or high-frequency EMA (6 EMAs per day) for fewer days would result in a better EMA completion rate and capture more hypoglycemia episodes. The secondary aim was to reduce the number of cognitive EMA tasks from 6 to 3. METHODS: Baseline cognitive tasks and psychological questionnaires were completed by all the participants (N=20), followed by EMA delivery of brief cognitive and self-report measures for 15 days while wearing a blinded continuous glucose monitor. These data were coded for the presence of hypoglycemia (<70 mg/dL) within 60 minutes of each EMA. The participants were randomized into group A (n=10 for group A and B; starting with 3 EMAs per day for 10 days and then switching to 6 EMAs per day for an additional 5 days) or group B (N=10; starting with 6 EMAs per day for 5 days and then switching to 3 EMAs per day for an additional 10 days). RESULTS: A paired samples 2-tailed t test found no significant difference in the completion rate between the 2 schedules (t17=1.16; P=.26; Cohen dz=0.27), with both schedules producing >80% EMA completion. However, more hypoglycemia episodes were captured during the schedule with the 3 EMAs per day than during the schedule with 6 EMAs per day. CONCLUSIONS: The results from this EMA optimization pilot guided key design decisions regarding the EMA frequency and study duration for the main GluCog study. The present report responds to the urgent need for systematic and detailed information on EMA study designs, particularly those using cognitive assessments coupled with physiological measures. Given the complexity of EMA studies, choosing the right instruments and assessment schedules is an important aspect of study design and subsequent data interpretation.

Neurocognition after motor vehicle collision and adverse post-traumatic neuropsychiatric sequelae within 8 weeks: Initial findings from the AURORA study.

BACKGROUND: Previous work has indicated that differences in neurocognitive functioning may predict the development of adverse post-traumatic neuropsychiatric sequelae (APNS). Such differences may be vulnerability factors or simply correlates of APNS-related symptoms. Longitudinal studies that measure neurocognitive functioning at the time of trauma are needed to determine whether such differences precede the development of APNS. METHODS: Here, we present findings from a subsample of 666 ambulatory patients from the AURORA (Advancing Understanding of RecOvery afteR trumA) study. All patients presented to EDs after a motor vehicle collision (MVC). We examined associations of neurocognitive test performance shortly after MVC with peritraumatic symptoms in the ED and APNS (depression, post-traumatic stress, post-concussive symptoms, and pain) 2 weeks and 8 weeks later. Neurocognitive tests assessed processing speed, attention, verbal reasoning, memory, and social perception. RESULTS: Distress in the ED was associated with poorer processing speed and short-term memory. Poorer short-term memory was also associated with depression at 2 weeks post-MVC, even after controlling for peritraumatic distress. Finally, higher vocabulary scores were associated with pain 2 weeks post-MVC. LIMITATIONS: Self-selection biases among those who present to the ED and enroll in the study limit generalizability. Also, it is not clear whether observed neurocognitive differences predate MVC exposure or arise in the immediate aftermath of MVC exposure. CONCLUSIONS: Our results suggest that processing speed and short-term memory may be useful predictors of trauma-related characteristics and the development of some APNS, making such measures clinically-relevant for identifying at-risk individuals.

How do we measure attention? Using factor analysis to establish construct validity of neuropsychological tests.

We investigated whether standardized neuropsychological tests and experimental cognitive paradigms measure the same cognitive faculties. Specifically, do neuropsychological tests commonly used to assess attention measure the same construct as attention paradigms used in cognitive psychology and neuroscience? We built on the "general attention factor", comprising several widely used experimental paradigms (Huang et al., 2012). Participants (n = 636) completed an on-line battery (TestMyBrain.org) of six experimental tests [Multiple Object Tracking, Flanker Interference, Visual Working Memory, Approximate Number Sense, Spatial Configuration Visual Search, and Gradual Onset Continuous Performance Task (Grad CPT)] and eight neuropsychological tests [Trail Making Test versions A & B (TMT-A, TMT-B), Digit Symbol Coding, Forward and Backward Digit Span, Letter Cancellation, Spatial Span, and Arithmetic]. Exploratory factor analysis in a subset of 357 participants identified a five-factor structure: (1) attentional capacity (Multiple Object Tracking, Visual Working Memory, Digit Symbol Coding, Spatial Span), (2) search (Visual Search, TMT-A, TMT-B, Letter Cancellation); (3) Digit Span; (4) Arithmetic; and (5) Sustained Attention (GradCPT). Confirmatory analysis in 279 held-out participants showed that this model fit better than competing models. A hierarchical model where a general cognitive factor was imposed above the five specific factors fit as well as the model without the general factor. We conclude that Digit Span and Arithmetic tests should not be classified as attention tests. Digit Symbol Coding and Spatial Span tap attentional capacity, while TMT-A, TMT-B, and Letter Cancellation tap search (or attention-shifting) ability. These five tests can be classified as attention tests.

The TestMyBrain Digital Neuropsychology Toolkit: Development and Psychometric Characteristics.

INTRODUCTION: To allow continued administration of neuropsychological evaluations remotely during the pandemic, tests from the not-for-profit platform, TestMyBrain.org (TMB), were used to develop the TMB Digital Neuropsychology Toolkit (DNT). This study details the psychometric characteristics of the DNT, as well as the infrastructure and development of the DNT. METHOD: The DNT was primarily distributed for clinical use, with (72.8%) of individuals requesting access for clinical purposes. To assess reliability and validity of the DNT, anonymous data from DNT test administrations were analyzed and compared to a large, non-clinical normative sample from TMB. RESULTS: DNT test scores showed acceptable to very good split-half reliability (.68-.99). Factor analysis revealed three latent factors, corresponding to processing speed, working memory, and a broader general cognitive ability factor that included perceptual reasoning and episodic memory. Average test scores were slightly poorer for the DNT sample than for the TMB comparison sample, as expected given the clinical use of the DNT. CONCLUSIONS: Initial estimates of reliability and validity of DNT tests support their use as digital measures of neuropsychological functioning. Tests within cognitive domains correlated highly with each other and demonstrated good reliability and validity. Future work will seek to validate DNT tests in specific clinical populations and determine best practices for using DNT outcome measures to assess engagement and psychological symptomatology.

Depression severity is associated with impaired facial emotion processing in a large international sample.

BACKGROUND: Depression is associated with biases in facial emotion processing, which have an impact on the course and treatment of depression. While decades of research have established a negativity bias in processing in depression, there is still a gap in our understanding of how depression severity impacts sensitivity to detecting differences in emotional faces. METHODS: We examined emotion sensitivity (ES), or the ability to to detect subtle differences in emotional faces, in a large, geographically and culturally diverse, web-based sample (N = 6598, age range = 18-96, 56.50% female, 66% Caucasian). Participants completed ES tasks (fear, anger, or happiness) and a Beck Depression Inventory-II, to determine depression severity. RESULTS: Depression severity was correlated with overall ES performance as well as ES performance for individual emotions. Higher depression scores were associated with poorer performance in detecting happiness, fear, and anger (ps < .001). Examining performance by region, Eastern countries showed significantly poorer ES performance compared to Western countries, and were significantly more depressed. LIMITATIONS: Our sample is non-clinical and self-selected. CONCLUSIONS: This study is an extension of existing research on emotional facial processing, with an approach that takes into consideration the heterogeneity of depression symptoms and corrects psychometric confounds of traditional emotion face processing paradigms. Overall, factors related to severity, task reliability, and facial stimuli should be considered in determining the potential mechanism of facial emotion processing in the onset and course of depression.