Mobile toolbox (MTB) remote measures of executive function and processing speed: development and validation.

OBJECTIVE: The ability to remotely monitor cognitive skills is increasing with the ubiquity of smartphones. The Mobile Toolbox (MTB) is a new measurement system that includes measures assessing Executive Functioning (EF) and Processing Speed (PS): Arrow Matching, Shape-Color Sorting, and Number-Symbol Match. The purpose of this study was to assess their psychometric properties. METHOD: MTB measures were developed for smartphone administration based on constructs measured in the NIH Toolbox® (NIHTB). Psychometric properties of the resulting measures were evaluated in three studies with participants ages 18 to 90. In Study 1 (N = 92), participants completed MTB measures in the lab and were administered both equivalent NIH TB measures and other external measures of similar cognitive constructs. In Study 2 (N = 1,021), participants completed the equivalent NIHTB measures in the lab and then took the MTB measures on their own, remotely. In Study 3 (N = 168), participants completed MTB measures twice remotely, two weeks apart. RESULTS: All three measures exhibited very high internal consistency and strong test-retest reliability, as well as moderately high correlations with comparable NIHTB tests and moderate correlations with external measures of similar constructs. Phone operating system (iOS vs. Android) had a significant impact on performance for Arrow Matching and Shape-Color Sorting, but no impact on either validity or reliability. CONCLUSIONS: Results support the reliability and convergent validity of MTB EF and PS measures for use across the adult lifespan in remote, self-administered designs.

Development and validation of an episodic memory measure in the Mobile Toolbox (MTB): Arranging Pictures.

INTRODUCTION: Arranging Pictures is a new episodic memory test based on the NIH Toolbox (NIHTB) Picture Sequence Memory measure and optimized for self-administration on a personal smartphone within the Mobile Toolbox (MTB). We describe evidence from three distinct validation studies. METHOD: In Study 1, 92 participants self-administered Arranging Pictures on study-provided smartphones in the lab and were administered external measures of similar and dissimilar constructs by trained examiners to assess validity under controlled circumstances. In Study 2, 1,021 participants completed the external measures in the lab and self-administered Arranging Pictures remotely on their personal smartphones to assess validity in real-world contexts. In Study 3, 141 participants self-administered Arranging Pictures remotely twice with a two-week delay on personal iOS smartphones to assess test-retest reliability and practice effects. RESULTS: Internal consistency was good across samples (ρxx = .80 to .85, p < .001). Test-retest reliability was marginal (ICC = .49, p < .001) and there were significant practice effects after a two-week delay (ΔM = 3.21 (95% CI [2.56, 3.88]). As expected, correlations with convergent measures were significant and moderate to large in magnitude (ρ = .44 to .76, p < .001), while correlations with discriminant measures were small (ρ = .23 to .27, p < .05) or nonsignificant. Scores demonstrated significant negative correlations with age (ρ = -.32 to -.21, p < .001). Mean performance was slightly higher in the iOS compared to the Android group (MiOS = 18.80, NiOS = 635; MAndroid = 17.11, NAndroid = 386; t(757.73) = 4.17, p < .001), but device type did not significantly influence the psychometric properties of the measure. Indicators of potential cheating were mixed; average scores were significantly higher in the remote samples (F(2, 850) = 11.415, p < .001), but there were not significantly more perfect scores. CONCLUSION: The MTB Arranging Pictures measure demonstrated evidence of reliability and validity when self-administered on personal device. Future research should examine the potential for cheating in remote settings and the properties of the measure in clinical samples.

Development and Validation of a Vocabulary Measure in the Mobile Toolbox.

OBJECTIVE: We describe the development of a new computer adaptive vocabulary test, Mobile Toolbox (MTB) Word Meaning, and validity evidence from 3 studies. METHOD: Word Meaning was designed to be a multiple-choice synonym test optimized for self-administration on a personal smartphone. The items were first calibrated online in a sample of 7,525 participants to create the computer-adaptive test algorithm for the Word Meaning measure within the MTB app. In Study 1, 92 participants self-administered Word Meaning on study-provided smartphones in the lab and were administered external measures by trained examiners. In Study 2, 1,021 participants completed the external measures in the lab and Word Meaning was self-administered remotely on their personal smartphones. In Study 3, 141 participants self-administered Word Meaning remotely twice with a 2-week delay on personal iPhones. RESULTS: The final bank included 1363 items. Internal consistency was adequate to good across samples (ρxx = 0.78 to 0.81, p < .001). Test-retest reliability was good (ICC = 0.65, p < .001), and the mean theta score was not significantly different upon the second administration. Correlations were moderate to large with measures of similar constructs (ρ = 0.67-0.75, p < .001) and non-significant with measures of dissimilar constructs. Scores demonstrated small to moderate correlations with age (ρ = 0.35 to 0.45, p < .001) and education (ρ = 0.26, p < .001). CONCLUSION: The MTB Word Meaning measure demonstrated evidence of reliability and validity in three samples. Further validation studies in clinical samples are necessary.

Face Name Associative Memory Exam and biomarker status in the ARMADA study: Advancing reliable measurement in Alzheimer's disease and cognitive aging.

The Face Name Associative Memory Exam (FNAME) was introduced into the NIH Toolbox as part of the ARMADA study and establishes normative data for diverse participants, ages 64 to 85+, and proposes cutoff scores between biomarker positive versus negative (+/-) groups. The FNAME was administered to 257 participants across the clinical spectrum with 122 having amyloid biomarkers. Linear regression explored the association between demographics and FNAME and between amyloid (+/-) groups. Receiver operating characteristic curves (ROC) identified performance thresholds that best discriminated between biomarker (+/-) individuals. Lower FNAME scores occurred in males, older ages, Black/African Americans, Hispanics, and biomarker-positive participants. ROC analyses demonstrated acceptable accuracy (0.73 to 0.77) but only when combined with clinical status. The diagnostic discrimination of amyloid positivity was acceptable but not excellent, suggesting the FNAME may be a better screening indicator of clinical status rather than amyloid deposition in cognitively normal individuals. Normative data are provided.

Uses of the NIH Toolbox® in Clinical Samples: A Scoping Review.

Background and Objectives: The NIH Toolbox® for the Assessment of Neurologic and Behavioral Function is a compilation of computerized measures designed to assess sensory, motor, emotional, and cognitive functioning of individuals across the life span. The NIH Toolbox was initially developed for use with the general population and was not originally validated in clinical populations. The objective of this scoping review was to assess the extent to which the NIH Toolbox has been used with clinical populations. Methods: Guided by the Joanna Briggs Methods Manual for Scoping Reviews, records were identified through searches of PubMed MEDLINE, PsycINFO, ClinicalTrials.gov, EMBASE, and ProQuest Dissertations and Theses Global (2008-2020). Database searches yielded 5,693 unique titles of original research that used at least one NIH Toolbox assessment in a sample characterized by any clinical diagnosis. Two reviewers screened titles, abstracts, and full texts for inclusion in duplicate. Conflicts at each stage of the review process were resolved by a group discussion. Results: Ultimately, 281 publication records were included in this scoping review (nJournal Articles = 104, nConference Abstracts = 84, nClinical Trial Registrations = 86, and nTheses/Dissertations = 7). The NIH Toolbox Cognition Battery was by far the most used of the 4 batteries in the measurement system (nCognition = 225, nEmotion = 49, nMotor = 29, and nSensation = 16). The most represented clinical category was neurologic disorders (n = 111), followed by psychological disorders (n = 39) and cancer (n = 31). Most (96.8%) of the journal articles and conference abstracts reporting the use of NIH Toolbox measures with clinical samples were published in 2015 or later. As of May 2021, these records had been cited a total of nearly 1,000 times. Discussion: The NIH Toolbox measures have been widely used among individuals with various clinical conditions across the life span. Our results lay the groundwork to support the feasibility and utility of administering the NIH Toolbox measures in research conducted with clinical populations and further suggest that these measures may be of value for implementation in fast-paced clinical settings as part of routine practice.

Challenges in Participant Engagement and Retention Using Mobile Health Apps: Literature Review.

BACKGROUND: Mobile health (mHealth) apps are revolutionizing the way clinicians and researchers monitor and manage the health of their participants. However, many studies using mHealth apps are hampered by substantial participant dropout or attrition, which may impact the representativeness of the sample and the effectiveness of the study. Therefore, it is imperative for researchers to understand what makes participants stay with mHealth apps or studies using mHealth apps. OBJECTIVE: This study aimed to review the current peer-reviewed research literature to identify the notable factors and strategies used in adult participant engagement and retention. METHODS: We conducted a systematic search of PubMed, MEDLINE, and PsycINFO databases for mHealth studies that evaluated and assessed issues or strategies to improve the engagement and retention of adults from 2015 to 2020. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Notable themes were identified and narratively compared among different studies. A binomial regression model was generated to examine the factors affecting retention. RESULTS: Of the 389 identified studies, 62 (15.9%) were included in this review. Overall, most studies were partially successful in maintaining participant engagement. Factors related to particular elements of the app (eg, feedback, appropriate reminders, and in-app support from peers or coaches) and research strategies (eg, compensation and niche samples) that promote retention were identified. Factors that obstructed retention were also identified (eg, lack of support features, technical difficulties, and usefulness of the app). The regression model results showed that a participant is more likely to drop out than to be retained. CONCLUSIONS: Retaining participants is an omnipresent challenge in mHealth studies. The insights from this review can help inform future studies about the factors and strategies to improve participant retention.

Translational implications of Th17-skewed inflammation due to genetic deficiency of a cadherin stress sensor.

Desmoglein 1 (Dsg1) is a cadherin restricted to stratified tissues of terrestrial vertebrates, which serve as essential physical and immune barriers. Dsg1 loss-of-function mutations in humans result in skin lesions and multiple allergies, and isolated patient keratinocytes exhibit increased proallergic cytokine expression. However, the mechanism by which genetic deficiency of Dsg1 causes chronic inflammation is unknown. To determine the systemic response to Dsg1 loss, we deleted the 3 tandem Dsg1 genes in mice. Whole transcriptome analysis of embryonic Dsg1-/- skin showed a delay in expression of adhesion/differentiation/keratinization genes at E17.5, a subset of which recovered or increased by E18.5. Comparing epidermal transcriptomes from Dsg1-deficient mice and humans revealed a shared IL-17-skewed inflammatory signature. Although the impaired intercellular adhesion observed in Dsg1-/- mice resembles that resulting from anti-Dsg1 pemphigus foliaceus antibodies, pemphigus skin lesions exhibit a weaker IL-17 signature. Consistent with the clinical importance of these findings, treatment of 2 Dsg1-deficient patients with an IL-12/IL-23 antagonist originally developed for psoriasis resulted in improvement of skin lesions. Thus, beyond impairing the physical barrier, loss of Dsg1 function through gene mutation results in a psoriatic-like inflammatory signature before birth, and treatment with a targeted therapy significantly improved skin lesions in patients.