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BackgroundIntellectual and developmental disabilities (IDDs) are associated with both cognitive challenges and difficulties in conceptual, social, and practical areas of living, commonly referred to as adaptive behavior (DSM-5). Although cross-sectional associations between intelligence or cognition and adaptive behavior have been reported in IDD populations, no study to date has examined whether developmental changes in cognition contribute to or track with changes in adaptive behavior. The present study sought to examine associations of longitudinal developmental change in domains of cognition (NIH Toolbox Cognition Battery, NIHTB-CB) and adaptive behavior domains (Vineland Adaptive Behavior Scales-3; VABS-3) including Socialization, Communication, and Daily Living Skills (DLS) over a two year period in a large sample of children, adolescents and young adults with IDD.MethodsThree groups were recruited, including those with fragile X syndrome, Down syndrome, and other/idiopathic intellectual disability. Eligible participants (n = 263) included those who were between 6 and 26 years (mage = 15.52, sd = 5.17) at Visit 1, and who had a diagnosis of, or suspected intellectual disability (ID), including borderline ID, with a mental age of at least 3.0 years. Participants were given cognitive and adaptive behavior assessments at two time points over a two year period (m = 2.45 years, range = 1.27 to 5.56 years). In order to examine the association of developmental change between cognitive and adaptive behavior domains, bivariate latent change score (BLCS) models were fit to compare change in the three cognitive domains measured by the NIHTB-CB (Fluid Cognition, Crystallized Cognition, Total Cognition) and the three adaptive behavior domains measured by the VABS-3 (Communication, DLS, and Socialization).ResultsOver a two year period, change in cognition (both Crystallized and Total Composites) was significantly and positively associated with change in daily living skills. Also, baseline cognition level predicted growth in adaptive behavior, however baseline adaptive behavior did not predict growth in cognition in any model.ConclusionsThe present study demonstrated that developmental changes in cognition and adaptive behavior are associated in children and young adults with IDD, indicating the potential for cross-domain effects of intervention. Notably, improvements in DLS emerged as a primary area of adaptive behavior that positively related to improvements in cognition. This work provides evidence for the clinical, "real life" meaningfulness of changes in cognition detected by the NIHTB-CB in IDD, and provides empirical support for the NIHTB-CB as a fit-for-purpose performance-based outcome measure for this population.

Validation of the Mobile Toolbox Faces and Names associative memory test is presented. Ninety‐two participants self‐administered Faces and Names in‐person; 956 self‐administered Faces and Names remotely but took convergent measures in person; and 123 self‐administered Faces and Names remotely twice, 14 days apart. Internal consistency (.76–.79) and test–retest reliability (ICC = .73) were acceptable. Convergent validity with WMS‐IV Verbal Paired Associates was satisfactory (immediate .54; delayed .58). The findings suggest the remotely administered Faces and Names is a reliable instrument. [ABSTRACT FROM AUTHOR]

Non‐pharmacological interventions include physical activity, biofield energy therapy, reiki, Tai chi, and therapeutic touch. However, no reports analyzed the effectiveness of biofield therapy on cognition and motor function performance in adult subjects. The study aimed to investigate the impact of remote biofield energy healing therapy on cognition and motor functioning in adults with self‐perceived neuropsychological impairments. This was a randomized double‐blind clinical trial that involved 114 participants with self‐perceived neuropsychological impairments. The participants were divided into three groups (control, sham control, and biofield intervention). Cognitive and motor function scores were assessed using the NIH Toolbox at baseline (day 0), day 90, and day 180. The biofield treatment group showed significant improvements in language function (p < 0.0001), working memory (p < 0.0001), and episodic memory (p < 0.0001) scores. Other cognitive functions also improved, although not statistically significant. The biofield intervention group also demonstrated significant enhancements (p < 0.05 to p < 0.0001) in locomotion, standing balance, dexterity, grip strength, and muscle endurance. No adverse effects were reported. The results suggest that remote biofield energy therapy is a safe, noninvasive intervention that improves cognitive and motor functions in adults. Further research is needed to understand its clinical benefits. [ABSTRACT FROM AUTHOR]

The NIH Toolbox offers brief, computerized measures of cognitive and psychosocial functioning. However, its psychometric properties were established among typically developing children and adolescents. The current study provides the first comprehensive assessment of its psychometric properties among young patients with congenital heart defects (CHD). We prospectively recruited 58 patients with CHD and 80 healthy controls between the ages of 6 and 17. Participants completed the NIH Toolbox Cognition and Emotion Batteries, a battery of clinician-administered neuropsychological tests, and ratings of their quality of life. Their parents also completed ratings of their functioning. On the Cognition Battery, we found expectable group differences and developmentally expected gains across ages. For the most part, composites and subtests were significantly correlated with neuropsychological measures of similar constructs. Higher scores were generally associated with ratings of better day-to-day functioning among children with CHD. On the Emotion Battery, we found no significant group differences, echoing prior research. For the most part, scales showed acceptable internal consistency among both groups. There was adequate construct coherence for most of questionnaires among healthy control but not participants with CHD. Correlations with a comparison tool were largely within expectable directions. The NIH Toolbox may provide a valid and useful assessment of cognitive functioning among youths with CHD. While it may offer reliable and valid scales of psychosocial functioning, further research is needed to understand the meaningfulness of the scales for participants with CHD. [ABSTRACT FROM AUTHOR]

Abstract Background Intellectual and developmental disabilities (IDDs) are associated with both cognitive challenges and difficulties in conceptual, social, and practical areas of living, commonly referred to as adaptive behavior (DSM–5). Although cross-sectional associations between intelligence or cognition and adaptive behavior have been reported in IDD populations, no study to date has examined whether developmental changes in cognition contribute to or track with changes in adaptive behavior. The present study sought to examine associations of longitudinal developmental change in domains of cognition (NIH Toolbox Cognition Battery, NIHTB-CB) and adaptive behavior domains (Vineland Adaptive Behavior Scales-3; VABS-3) including Socialization, Communication, and Daily Living Skills (DLS) over a two year period in a large sample of children, adolescents and young adults with IDD. Methods Three groups were recruited, including those with fragile X syndrome, Down syndrome, and other/idiopathic intellectual disability. Eligible participants (n = 263) included those who were between 6 and 26 years (mage = 15.52, sd = 5.17) at Visit 1, and who had a diagnosis of, or suspected intellectual disability (ID), including borderline ID, with a mental age of at least 3.0 years. Participants were given cognitive and adaptive behavior assessments at two time points over a two year period (m = 2.45 years, range = 1.27 to 5.56 years). In order to examine the association of developmental change between cognitive and adaptive behavior domains, bivariate latent change score (BLCS) models were fit to compare change in the three cognitive domains measured by the NIHTB-CB (Fluid Cognition, Crystallized Cognition, Total Cognition) and the three adaptive behavior domains measured by the VABS-3 (Communication, DLS, and Socialization). Results Over a two year period, change in cognition (both Crystallized and Total Composites) was significantly and positively associated with change in daily living skills. Also, baseline cognition level predicted growth in adaptive behavior, however baseline adaptive behavior did not predict growth in cognition in any model. Conclusions The present study demonstrated that developmental changes in cognition and adaptive behavior are associated in children and young adults with IDD, indicating the potential for cross-domain effects of intervention. Notably, improvements in DLS emerged as a primary area of adaptive behavior that positively related to improvements in cognition. This work provides evidence for the clinical, “real life” meaningfulness of changes in cognition detected by the NIHTB-CB in IDD, and provides empirical support for the NIHTB-CB as a fit-for-purpose performance-based outcome measure for this population.

Objective: Adults with type 1 diabetes (T1D) face an increased risk for cognitive decline and dementia. Diabetes-related and vascular risk factors have been linked to cognitive decline using detailed neuropsychological testing; however, it is unclear if cognitive screening batteries can detect cognitive changes associated with aging in T1D. Method: 1,049 participants with T1D (median age 59 years; range 43–74) from the Diabetes Control and Complications Trial (DCCT), and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study, completed the NIH Toolbox Cognition Battery (NIHTB-C) and Montreal Cognitive Assessment (MoCA). Neuropsychological assessments, depression, glycated hemoglobin levels (HbA1c), severe hypoglycemia, T1D complications, and vascular risk factors were assessed repeatedly over 32 years to determine associations with current NIHTB-C performance. Available cognitive data was clinically adjudicated to determine cognitive impairment status. Results: NIHTB-C scores had moderate associations (r = 0.36–0.53) with concurrently administered neuropsychological tests. In multivariate models, prior severe hypoglycemic episodes, depression symptoms, nephropathy, lower BMI, and higher HbA1c and LDL cholesterol were associated with poorer NIHTB-C Fluid Cognition Composite scores. The NIHTB-C adequately detected adjudicated cognitive impairment (Area Under the Curve = 0.86; optimal cut score ≤90). The MoCA performed similarly (Area Under the Curve = 0.83; optimal cut score ≤25). Conclusions: The NIHTB-C is sensitive to the cognitive effects of diabetes-related and vascular risk factors, correlated with neuropsychological testing, and accurately detects adjudicated cognitive impairment. These data support its use as a screening test in middle to older aged adults with T1D to determine if referral for detailed neuropsychological assessment is needed. [ABSTRACT FROM AUTHOR]

Degenerative cervical myelopathy (DCM) is a leading cause of age-related non-traumatic spinal cord disorders resulting from chronic degeneration of the cervical spine. While traditional clinical assessments rely on patient-reported measures, this study used the NIH Toolbox Motor Battery (NIHTBm) as an objective, quantitative measure to determine DCM severity. The objective is to define NIHTBm cutoff values that can accurately classify the severity of DCM neuromotor dysfunction. A case-controlled pilot study of patients with DCM and age-matched controls. The focus was an in-depth quantitative motor assessment using the NIHTBm to understand the severity of neuromotor deficits due to degenerative spine disease. Motor assessments, dexterity, grip strength, balance, and gait speed were measured in 45 DCM patients and 37 age-matched healthy subjects (HC). Receiver operating curve (ROC) analysis determined cutoff values for mild and moderate-to-severe myelopathy which were validated by comparing motor assessment scores with disability scores. The ROC curves identified thresholds for mild dexterity impairment (T-score range 38.4 − 33.5, AUC 0.77), moderate-to-severe dexterity impairment (< 33.5, AUC 0.70), mild grip strength impairment (47.4 − 32.0, AUC 0.80), moderate-to-severe grip strength impairment (< 32.0, AUC 0.75), mild balance impairment (36.4 − 33.0, AUC 0.61), and moderate-to-severe balance impairment (< 33.0, AUC 0.78). Mild gait speed impairment was defined as 0.78–0.6 m/sec (AUC 0.65), while moderate-to-severe gait speed impairment was < 0.6 m/sec (AUC 0.65). The NIHTB motor score cutoff points correlated negatively with the DCM neck disability index (NDI) and showed balance and dexterity measures as independent indicators of DCM dysfunction. The use of NIHTB allows for precise delineation of DCM severity by establishing cutoff values corresponding to mild and moderate-to-severe myelopathy. The use of NIHTB in DCM allows enhanced clinical precision, enabling clinicians to better pinpoint specific motor deficits in DCM and other neurological disorders with motor deficits, including stroke and traumatic brain injury (TBI). Furthermore, the utility of objective assessment, NIHTB, allows us to gain a better understanding of the heterogeneity of DCM, which will enhance treatment strategies. This study serves as a foundation for future research to facilitate the discovery of innovative treatment strategies for DCM and other neurological conditions. [ABSTRACT FROM AUTHOR]

Timely detection of cognitive impairment (CI) is critical for the wellbeing of elderly individuals. The MyCog assessment employs two validated iPad-based measures from the NIH Toolbox® for Assessment of Neurological and Behavioral Function (NIH Toolbox). These measures assess pivotal cognitive domains: Picture Sequence Memory (PSM) for episodic memory and Dimensional Change Card Sort Test (DCCS) for cognitive flexibility. The study involved 86 patients and explored diverse machine learning models to enhance CI prediction. This encompassed traditional classifiers and neural-network-based methods. After 100 bootstrap replications, the Random Forest model stood out, delivering compelling results: precision at 0.803, recall at 0.758, accuracy at 0.902, F1 at 0.742, and specificity at 0.951. Notably, the model incorporated a composite score derived from a 2-parameter higher order item response theory (HOIRT) model that integrated DCCS and PSM assessments. The study's pivotal finding underscores the inadequacy of relying solely on a fixed composite score cutoff point. Instead, it advocates for machine learning models that incorporate HOIRT-derived scores and encompass relevant features such as age. Such an approach promises more effective predictive models for CI, thus advancing early detection and intervention among the elderly. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Olfactory decline is associated with cognitive decline in aging, amnestic mild cognitive impairment (aMCI), and amnestic dementia associated with Alzheimer's disease neuropathology (ADd). The National Institutes of Health Toolbox Odor Identification Test (NIHTB‐OIT) may distinguish between these clinical categories. METHODS: We compared NIHTB‐OIT scores across normal cognition (NC), aMCI, and ADd participants (N = 389, ≥65 years) and between participants positive versus negative for AD biomarkers and the APOE ε4 allele. RESULTS: NIHTB‐OIT scores decreased with age (p < 0.001) and were lower for aMCI (p < 0.001) and ADd (p < 0.001) compared to NC participants, correcting for age and sex. The NIHTB‐OIT detects aMCI (ADd) versus NC participants with 49.4% (56.5%) sensitivity and 88.8% (89.5%) specificity. NIHTB‐OIT scores were lower for participants with positive AD biomarkers (p < 0.005), but did not differ based on the APOE ε4 allele (p > 0.05). DISCUSSION: The NIHTB‐OIT distinguishes clinically aMCI and ADd participants from NC participants. Highlights: National Institutes of Health Toolbox Odor Identification Test (NIHTB‐OIT) discriminated normal controls from mild cognitive impairment.NIHTB‐OIT discriminated normal controls from Alzheimer's disease dementia.Rate of olfactory decline with age was similar across all diagnostic categories.NIHTB‐OIT scores were lower in participants with positive Alzheimer's biomarker tests.NIHTB‐OIT scores did not differ based on APOE genotype. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to evaluate the psychometric properties of the culturally adapted NIH Toolbox African Languages® when used in Swahili and Dholuo-speaking children in western Kenya. Method: Swahili-speaking participants were recruited from Eldoret and Dholuo-speaking participants from Ajigo; all were <14 years of age and enrolled in primary school. Participants completed a demographics questionnaire and five fluid cognition tests of the NIH Toolbox® African Languages program, including Flanker, Dimensional Change Card Sort (DCCS), Picture Sequence Memory, Pattern Comparison, and List Sorting tests. Statistical analyses examined aspects of reliability, including internal consistency (in both languages) and test–retest reliability (in Dholuo only). Results: Participants included 479 children (n = 239, Swahili-speaking; n = 240, Dholuo-speaking). Generally, the tests had acceptable psychometric properties for research use within Swahili- and Dholuo-speaking populations (mean age = 10.5; SD = 2.3). Issues related to shape identification and accuracy over speed limited the utility of DCCS for many participants, with approximately 25% of children unable to match based on shape. These cultural differences affected outcomes of reliability testing among the Dholuo-speaking cohort, where accuracy improved across all five tests, including speed. Conclusions: There is preliminary evidence that the NIH Toolbox ® African Languages potentially offers a valid assessment of development and performance using tests of fluid cognition in Swahili and Dholuo among research settings. With piloting underway across other diverse settings, future research should gather additional evidence on the clinical utility and acceptability of these tests, specifically through the establishment of norming data among Kenyan regions and evaluating these psychometric properties. [ABSTRACT FROM AUTHOR]

Speeded Matching (SpM) is a new processing speed match-to-sample test within the NIH Toolbox Cognitive Battery. It was designed to developmentally extend feasibility to younger children or individuals with intellectual or developmental disabilities (IDD). SpM reduces cognitive demands to tapping an identical match as opposed to judging and indicating whether two stimuli are identical. In this study, we piloted SpM among 148 participants with fragile X syndrome, Down syndrome, or other intellectual disabilities (chronological age mean = 17.8 years, sd = 5.4; nonverbal mental age mean = 65 months, sd = 19.4). SpM had a high feasibility (96%) and internal consistency (rxx = 0.98). It converged well with other measures of processing speed, fluid cognition, and nonverbal mental age and diverged appropriately from crystallized cognitive skills. The correlation between nonverbal mental age and SpM in the IDD sample was not significantly different than the correlation between chronological age and SpM in a separate sample of 118 neurotypical children (age mean = 3.9 years sd = 0.8). This study provides initial evidence for the reliability and validity of the new SpM task, which may be appropriate as an outcome measure of processing speed for future clinical trials. It is more feasible than tasks designed for adults; it is brief, easy to administer, and engaging for young children and older individuals with lower mental ages associated with IDD.

Quantifying hearing acuity is increasingly important across a wide range of research areas in the behavioral and neurosciences. Scientists have relied on either self-reported hearing status or the availability of diagnostic hearing assessment in past studies. There remains a need for a valid and reliable assessment of auditory sensitivity that can provide estimates of the magnitude of hearing loss, if present, without requirements for professional audiologists, facilities, and equipment that are needed to conduct a diagnostic hearing assessment. The goal of this experiment was to validate the NIH Toolbox® Hearing Threshold Test (HTT), a tablet-based hearing assessment available via iPad application that uses consumer-grade headphones, on a clinical sample of children and adults with varying degrees of hearing acuity. Electroacoustic analysis of the hearing assessment application and headphones demonstrated acoustic outputs within established conformity standards for hearing assessment. Twenty-seven children and 63 adults participated in a standard diagnostic hearing assessment and the experimental tablet-based assessment. The results showed that thresholds from the tablet-based assessment were highly correlated with thresholds from the clinical hearing assessment (r =.83–.93) for children and adults for all frequencies and across a range of levels of hearing acuity. The HTT also met clinical test–retest reliability standards (Cronbach's α >.86). The tablet-based hearing assessment provides acceptable estimates of hearing levels for children and adults when diagnostic audiometric assessment capabilities are not available. [ABSTRACT FROM AUTHOR]

Despite the clinically significant impact of executive dysfunction on the outcomes of adolescents and young adults with autism spectrum disorders (ASD), we lack a clear understanding of its prevalence, profile, and development. To address this gap, we administered the NIH Toolbox Cognition Battery to a cross-sectional Intelligence Quotient (IQ) case-matched cohort with ASD (n = 66) and typical development (TD; n = 66) ages 12-22. We used a general linear model framework to examine group differences in task performance and their associations with age. Latent profile analysis (LPA) was used to identify subgroups of individuals with similar cognitive profiles. Compared to IQ case-matched controls, ASD demonstrated poorer performance on inhibitory control (P

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. [ABSTRACT FROM AUTHOR]

To quantify neuropsychiatric symptoms reported by individuals with Post-Acute Sequelae of COVID-19 (PASC) using the NIH Toolbox for Assessment of Neurological and Behavioral Function (NIHTB) and Patient-Reported Outcomes Measurement Information System (PROMIS). 30 PASC (20 women, 21–63 years) and 27 control (16 women, 25–68 years) participants completed three NIHTB batteries and selected PROMIS tests. Group differences on fully corrected T-scores were evaluated using analysis of covariance and Cohen's d effect sizes. A linear regression model predicted the effects from time since diagnosis. PASC had poorer emotional health and motor function than controls, including poorer locomotion, endurance and dexterity, but normal cognitive function, ∼7 months post-infection. PASC participants had a steeper age-related decline on the 2-Minute Walk Endurance Test than controls. T-scores on four cognitive and three motor tests improved with longer time since diagnosis. NIHTB and PROMIS captured the poorer emotional health and motor function in PASC, including the novel findings of deficits in locomotion and dexterity. The normal cognitive performance suggests subclinical effects that may be compensated by neural and cognitive reserves, and manifested subjectively by the negative psychological effects and fatigue. The persistent emotional and psychiatric symptoms necessitate mental health treatment be prioritized. [ABSTRACT FROM AUTHOR]

The NIH Toolbox includes a cognitive battery that provides an Early Childhood Composite score for children age 3–7. However, very few studies have evaluated feasibility when it is used in the youngest segment of this age range—3-year-olds. The current study evaluated performance on the four cognitive subtests composing the early childhood composite, two of which assess executive function, in a large sample of 3-year-olds enrolled in a Vanguard pilot of the National Children's Study. Results found that in a cohort of 609 3-year-olds (mean age = 39.6 months, SD = 1.6, 53% male, 64% White, 87% Non-Hispanic) who were administered four subtests included in the Early Childhood Composite, up to approximately 30% were unable to pass practice items on the Flanker, Dimensional Change Card Sort, and Picture Sequence Memory, whereas only approximately 3% were unable to pass practice items on the Picture Vocabulary Test. Furthermore, of those that did pass practice and achieve scores on the subtests, approximately 70% and 80% performed at or below chance level on the executive function tasks (Flanker and Dimensional Change Card Sort) and Picture Sequence Memory, respectively. Ultimately, the average 3-year-old has difficulty with three of the four NIH Toolbox tasks composing the Early Childhood Composite and may not yet have developed the requisite skills. These findings indicate that changes compatible with the developmental level of preschoolers are recommended to increase the feasibility and effectiveness of the NIH Toolbox in measuring individual cognition differences in 3-year-old children. [ABSTRACT FROM AUTHOR]

Introduction: The National Institutes of Health (NIH) Toolbox (NIHTB) provides computerized measures of cognition, emotion, sensation, and motor abilities across the lifespan. The ARMADA (Assessing Reliable Measurement in Alzheimer's Disease and Cognitive Aging) study validated the NIHTB in individuals across the cognitive aging spectrum. This article reports the characteristics of our sample of participants. Methods: Participants were recruited across nine sites and classified clinically as cognitively normal (NC), with mild cognitive impairment (MCI), or with dementia of the Alzheimer's type (DAT.) They completed the NIHTB at multiple time points and many had at least one Alzheimer's biomarker previously obtained. Results: Groups differed with respect to dementia severity levels, as anticipated, but were well‐matched across many demographic characteristics. Discussion: The ARMADA study demographics and baseline characteristics provide a suitable sample for validating the NIHTB across the cognitive aging spectrum. Other enriched samples (African American participants, Spanish NIHTB, 85+ years of age) will be reported elsewhere. Highlights: There is a need for assessments that can detect the early stages of cognitive decline in older adults.The ARMADA (Assessing Reliable Measurement in Alzheimer's Disease and Cognitive Aging) study will validate the National Institutes of Health (NIH) Toolbox across the aging spectrum, including mild cognitive impairment (MCI) and dementia of the Alzheimer's type (DAT).Here we report the characteristics of participants.Groups were well‐matched across most demographic characteristics, and clinical characteristics differed as expected.ARMADA study cohorts reflect their respective clinical syndromes for validating the NIH Toolbox. [ABSTRACT FROM AUTHOR]

Objective: Older adults with exceptional memory function, designated "SuperAgers," include individuals over age 80, with episodic memory at least as good as individuals ages 50s–60s. The Northwestern University SuperAging cohort is defined by performance on an established test of verbal memory. The purpose of this study was to determine if superior verbal memory extends to nonverbal memory in SuperAgers by examining differences in the National Institutes of Health Toolbox® (NIHTB) between older adults with exceptional memory and those with average-for-age cognition. Method: SuperAgers (n  = 46) and cognitively average-for-age older adults (n  = 31) completed a comprehensive neuropsychological battery and the NIHTB Cognition module. Multiple linear regressions were used to examine differences on subtests between groups. Results: There was a significant effect of group on the Picture Sequence Memory score, (p = .007), such that SuperAgers had higher scores than cognitively average-for-age older adults. There were no other group effects across other non-episodic memory NIHTB Cognition measures. Conclusions: Findings from this study demonstrated stronger performance on the memory measure of the NIHTB in SuperAgers compared to cognitively average-for-age older adults demonstrating superior memory in not only verbal but also nonverbal episodic memory in this group. Additionally, this study adds to the literature validating the NIHTB in older adults, particularly in a novel population of adults over age 80 with exceptional memory. [ABSTRACT FROM AUTHOR]

Abstract 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.

The Adolescent Brain Cognitive Development (ABCD) study is poised to be the largest single-cohort long-term longitudinal study of neurodevelopment and child health in the United States. Baseline data on N= 4521 children aged 9-10 were released for public access on November 2, 2018. In this paper we performed principal component analyses of the neurocognitive assessments administered to the baseline sample. The neurocognitive battery included seven measures from the NIH Toolbox as well as five other tasks. We implemented a Bayesian Probabilistic Principal Components Analysis (BPPCA) model that incorporated nesting of subjects within families and within data collection sites. We extracted varimax-rotated component scores from a three-component model and associated these scores with parent-rated Child Behavior Checklist (CBCL) internalizing, externalizing, and stress reactivity. We found evidence for three broad components that encompass general cognitive ability, executive function, and learning/memory. These were significantly associated with CBCL scores in a differential manner but with small effect sizes. These findings set the stage for longitudinal analysis of neurocognitive and psychopathological data from the ABCD cohort as they age into the period of maximal adolescent risk-taking.

Supplemental Digital Content is Available in the Text. Chronic pain domains and their relationship with individuals' personality, psychology, social interaction, ability, beliefs, attitudes, and expectations, which correlates with unique brain network signatures. Chronic pain is a multidimensional pathological state. Recent evidence suggests that specific brain properties and patients' psychological and physical traits are distorted in chronic pain patients. However, the relationship between these alterations and pain dimensions remains poorly understood. Here, we first evaluated multiple dimensions of chronic pain by assessing a broad battery of pain-related questionnaire scores (23 outcomes) of 107 chronic low back pain patients and identified 3 distinct chronic pain domains: magnitude, affect & disability, and quality. Second, we investigated the pain domains relationship with measures of personality, social interaction, psychological traits, and ability traits (77 biopsychosocial & ability [biopsy&ab] outcomes). Pain magnitude (out-of-sample [OOS] r 2 = 0.33) is associated with emotional control, attention, and working memory, with higher pain scores showing lower capacity to regulate and adapt behaviorally. Pain affect & disability (OOS r 2 = 0.79) associated with anxiety, catastrophizing and social relationships dysfunction. Pain quality did not relate significantly to biopsy&ab variables. Third, we mapped these 3 pain domains to brain functional connectivity. Pain magnitude mainly associated with the sensorimotor and the cingulo-opercular networks (OOS r 2 = 0.41). Pain affect & disability related to frontoparietal and default mode networks (OOS r 2 = 0.35). Pain quality integrated sensorimotor, auditory, and cingulo-opercular networks (OOS r 2 = 0.43). Mediation analysis could link functional connectivity and biopsy&ab models to respective pain domains. Our results provide a global overview of the complexity of chronic pain, showing how underlying distinct domains of the experience map to different biopsy&ab correlates and underlie unique brain network signatures. [ABSTRACT FROM AUTHOR]

The NIH Toolbox Cognition Battery (NIHTB-CB) was developed for epidemiological and longitudinal studies across a wide age span. Such a tool may be useful for intervention trials in conditions characterized by intellectual disability (ID), such as Williams syndrome (WS). Three NIHTB-CB tasks, including two executive functioning (Flanker, Dimensional Change Card Sort) and one episodic memory (Picture Sequence Memory) task, were given to 47 individuals with WS, ages 4 to 50, to evaluate feasibility (i.e., proportion of valid administrations) in this population. Findings indicated that NIHTB-CB tests showed good feasibility. Flanker and DCCS age-corrected scores were negatively correlated with age and showed floor effects, indicating these scores may not be useful for quantifying performance on these NIHTB-CB tests in ID. [ABSTRACT FROM AUTHOR]

Purpose: We previously reported seizure and EEG outcomes of the ESTEL study (Electrical Stimulation of Thalamus for Epilepsy of Lennox-Gastaut phenotype). To assess potential cognitive and behavioral changes during chronic, duty-cycle stimulation of bilateral thalamic centromedian nucleus, we compared standardized cognitive and behavioral measurements, as well as caregiver assessments of disability/severity, before implantation and after 3-months stimulation.Methods: Twenty patients with LGS (17-37 years;13 females) were studied; one participant was not randomized due to DBS device removal, with outcomes of 19 remaining participants reported here. Cognitive and behavioral measurements were performed at baseline (i.e., before DBS implantation), at the end of the blinded stimulation phase, and at study exit. Instruments measured cognition (NIH toolbox cognitive battery, NIHTB-CB), adaptive skills (ABAS-3), epilepsy severity (GASE) and disability (GAD), quality of life (QOLIE-31), and depression (PHQ-9). Changes in scores after 3-months of stimulation relative to baseline were explored using Wilcoxon matched-pairs signed rank tests.Results: After 3-months of stimulation, caregiver-reported epilepsy severity (GASE) and disability (GAD) improved (p<0.05). No other instrument showed a significant change from baseline. Measurements that required direct participant involvement, rather than caregivers, was completed by only a subset of higher-functioning individuals (NIHTB-CB, n = 13; QOLIE-31, n = 3; and PHQ-9, n = 6). In addition to cognitive impairments, behavioral and physical limitations were common obstacles to instrument completion. Standardized scores were hindered by 'floor effects'; however, raw scores better reflected clinical impressions of participants' functioning and were more sensitive to caregiver-reported changes following treatment.Conclusion: DBS treatment is associated with reduced epilepsy severity and disability in young adults with LGS. Performing cognitive and behavioral outcome measurement in patients with cognitive impairment is challenging but possible and requires careful selection of instruments and modifications of score interpretation to avoid floor effects. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to establish the utility of the NIH Toolbox as a cognitive screener of executive functions in the clinical context. Additionally, we aimed to investigate whether age and time on transfusion were related to executive function performance. Method: Twenty-eight children and adolescents with sickle cell anemia (SCA) between 8 and 18 years (M = 13.28, SD = 3.05) on transfusion treatment were included. Participants completed five NIH Toolbox tasks (three executive function tasks and two non-executive function control tasks). Results: Mean scores on one of the three executive function measures (inhibitory control) fell below the average range (M = 81.36, SD = 14.01) with approximately 70% of children from both groups below the average range. Scores for processing speed (M = 86.82, SD = 22.01) and cognitive flexibility (M = 85.75, SD = 12.67) were low averages. As expected, scores on non-executive measures (language and memory) fell within the average range. No significant differences were observed between children with silent stroke and no stroke on executive function measures. Older age (p <.01) and length of time on transfusion (p <.05) predicted lower inhibitory control scores. Conclusions: Findings provide evidence for poor development of inhibitory control with age in this patient population. As the NIH Toolbox successfully highlighted expected deficits in this patient population, this study supports the use of this tool as a brief screening measure for children with SCD. The clinical and theoretical implications of the findings are discussed. [ABSTRACT FROM AUTHOR]

Introduction: Early detection of cognitive decline in older adults is a public health priority. Advancing Reliable Measurement in Alzheimer's Disease and Cognitive Aging (ARMADA), a multisite study, is validating cognition, emotion, motor, and sensory modules of the National Institutes of Health Toolbox for Assessment of Neurological and Behavioral Function (NIHTB) in the aging spectrum from cognitively normal to dementia of the Alzheimer's type (DAT). Methods: Participants 65 to 85 years old, in demographic groups racially proportional to the general US population, are recruited in one of three groups to validate the NIHTB: cognitively normal, amnestic mild cognitive impairment (aMCI), or mild DAT. Additional special emphasis cohorts include (1) Blacks in the three clinical groups; (2) Spanish‐speakers in the three clinical groups; (3) cognitively normal, population‐proportional, over age 85. Discussion: Longitudinal study will determine whether NIHTB can predict cognitive decline and is associated with Alzheimer's disease biomarkers. Here, we detail the methods for the ARMADA study. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that gut microbes modulate brain plasticity via the bidirectional gut-brain axis and play a role in stroke rehabilitation. However, the microbial species alterations associated with stroke and their correlation with functional outcome measures following acute stroke remain unknown. Here we measure post-stroke gut dysbiosis and how it correlates with gut permeability and cognitive functions in 12 stroke participants, 18 controls with risk factors for stroke, and 12 controls without risk factors. Stool samples were used to measure the microbiome with whole genome shotgun sequencing and leaky gut markers. We genotyped APOE status and measured diet composition and motor, cognitive, and emotional status using NIH Toolbox. We used linear regression methods to identify gut microbial associations with cognitive and emotional assessments. We did not find significance differences between the two control groups. In contrast, the bacteria populations of the Stroke group were statistically dissimilar from the control groups. Relative abundance analysis revealed notable decreases in butyrate-producing microbial taxa, secondary bile acid-producing taxa, and equol-producing taxa. The Stroke group had higher levels of the leaky gut marker alpha-1-antitrypsin in the stool than either of the groups and several taxa including Roseburia species (a butyrate producer) were negatively correlated with alpha-1-antitrypsin. Stroke participants scored lower on memory testing than those in the two control groups. Stroke participants with more Roseburia performed better on the picture vocabulary task; more Bacteroides uniformis (a butyrate producer) and less Escherichia coli (a pro-inflammatory species) reported higher levels of self-efficacy. Intakes of fiber, fruit and vegetable were lower, but sweetened beverages were higher, in the Stroke group compared with controls. Vegetable consumption was correlated with many bacterial changes among the participants, but only the species Clostridium bolteae, a pro-inflammatory species, was significantly associated with stroke. Our findings indicate that stroke is associated with a higher abundance of proinflammatory species and a lower abundance of butyrate producers and secondary bile acid producers. These altered microbial communities are associated with poorer functional performances. Future studies targeting the gut microbiome should be developed to elucidate whether its manipulation could optimize rehabilitation and boost recovery.

Background: The Cognitive Battery of the National Institutes of Health Toolbox (NIH-TB) is a collection of assessments that have been adapted and normed for administration across the lifespan and is increasingly used in large-scale population-level research. However, despite increasing adoption in longitudinal investigations of neurocognitive development, and growing recommendations that the Toolbox be used in clinical applications, little is known about the long-term temporal stability of the NIH-TB, particularly in youth. Methods: The present study examined the long-term temporal reliability of the NIH-TB in a large cohort of youth (9–15 years-old) recruited across two data collection sites. Participants were invited to complete testing annually for 3 years. Results: Reliability was generally low-to-moderate, with intraclass correlation coefficients ranging between 0.31 and 0.76 for the full sample. There were multiple significant differences between sites, with one site generally exhibiting stronger temporal stability than the other. Conclusions: Reliability of the NIH-TB Cognitive Battery was lower than expected given early work examining shorter test-retest intervals. Moreover, there were very few instances of tests meeting stability requirements for use in research; none of the tests exhibited adequate reliability for use in clinical applications. Reliability is paramount to establishing the validity of the tool, thus the constructs assessed by the NIH-TB may vary over time in youth. We recommend further refinement of the NIH-TB Cognitive Battery and its norming procedures for children before further adoption as a neuropsychological assessment. We also urge researchers who have already employed the NIH-TB in their studies to interpret their results with caution. [ABSTRACT FROM AUTHOR]

Adults with type 1 diabetes (T1D) are considered at increased risk for cognitive impairment and accelerated brain aging. However, longitudinal data on cognitive impairment and dementia in this population are scarce. To identify risk factors associated with cognitive performance and cognitive impairment in a longitudinal sample of older adults with T1D. We analyzed data collected as part of the Wireless Innovation for Seniors with Diabetes Mellitus (WISDM) Study, in which 22 endocrinology practices participated. Randomized participants with T1D ≥60 years of age who completed at least one cognitive assessment were included in this study (n = 203). Cognitive impairment was classified using published recommendations. Older age, male sex, non-private health insurance, worse daily functioning, diagnosis of neuropathy, and longer duration of diabetes were associated with worse cognitive performance, but not cognitive impairment. 49 % and 39 % of the sample met criteria for cognitive impairment at baseline and 52 weeks respectively. Of the participants that had data at both time points, 10 % were normal at baseline and impaired at 52 weeks and 22 % of participants (44 % of those classified with cognitive impairment at baseline) reverted to normal over 52 weeks. This study indicated that several demographic and clinical characteristics are associated with worse cognitive performance in older adults with T1D, but there were no associations between these characteristics and cognitive impairment defined by NIH Toolbox cognitive impairment criteria. Caution is warranted when assessing cognition in older adults with T1D, as a large percentage of those identified as having cognitive impairment at baseline reverted to normal after 52 weeks. There is need for future studies on the interrelationship of cognition and aging to better understand the effects of T1D on cognitive health, to improve clinical monitoring and help mitigate the risk of dementia in this population. • Adults with T1D have increased risk factors for cognitive impairment and dementia. • Longitudinal data on cognitive impairment and dementia in this population are scarce. • Demographic and clinical characteristics are associated with cognitive performance. • Almost half of those with cognitive impairment at baseline reverted to normal. [ABSTRACT FROM AUTHOR]

Objective: To determine phenotypic differences between Black and White patients with Parkinson's disease (PD).Design/methods: Patients with PD in a movement disorders clinic were approached to participate. After consent, a battery of tests was completed, including MDS-UPDRS Part III and the motor domains of the NIH Toolbox, Montreal Cognitive Assessment, Single Digit Modality Test, Patient-Reported Outcomes Measurement Information System (PROMIS) measures, Parkinson's Disease Questionnaire (PDQ39), Schwab and England, Epworth Sleepiness Scale, UPSIT smell test, and others.Results: Twenty-four Black PD and 25 White PD patients participated. There were no differences in demographics and MDS-UPDRS Part III scores. White PD participants performed better on the 4-m walk gait speed test (p < 0.0005), standing balance test (p < 0.001), Montreal Cognitive Assessment (p < 0.0005), and Single Digit Modality Test (p < 0.005). Black PD participants had lower scores on PROMIS Satisfaction with Participation (p = 0.023), PROMIS Physical Function Mobility (p = 0.007), total PDQ39 (p = 0.008), PDQ39 mobility (p = 0.012), PDQ39 ADL (p = 0.014), PDQ39 cognition (p = 0.023), and PDQ39 body discomfort (p = 0.041) scales.Conclusions: Significant differences were found in motor, non-motor and quality of life scales in Black and White PD participants with similar demographics. Further work will need to be done to identify the underlying reasons and ways to mitigate these disparities. [ABSTRACT FROM AUTHOR]

Purpose Hypoparathyroid patients describe cognitive deficits, yet data regarding objective assessment of cognitive function are limited. We assessed cognition in a pilot study of hypoparathyroid patients using the National Institutes of Health Toolbox® Adult Cognitive Battery (NIHTB-CB). We also sought to determine whether cognition relates to emotion, quality of life, and hypoparathyroidism-related biochemistries. Methods Nineteen hypoparathyroid patients were studied. Objective cognition was assessed with NIHTB-CB. Impairment was defined as fully demographically adjusted T-score < 1.5 SD in at least 1 cognitive domain or < 1 SD in 2 or more domains. Results Of the 19 participants (17 women; median age 49; 18 postsurgical), impaired demographically adjusted NIHTB-CB cognition scores were observed in 13 subjects (68%). Cognition scores correlated with self-reported perception of general health. Processing speed was the most commonly impaired cognitive domain, with T-scores that were ≤2 SD in 6 subjects (32%). Processing speed correlated with serum calcium (r = 0.53, P  = 0.023) and inversely with serum phosphate (r = −0.48, P  = 0.042) levels. Conclusions Impaired cognition using the NIHTB-CB was common in this small pilot cohort of hypoparathyroid patients. Slower processing speed was present and associated with lower serum calcium and higher serum phosphate levels. Larger controlled studies with additional neuropsychological testing are needed to investigate cognitive function in hypoparathyroidism. [ABSTRACT FROM AUTHOR]

Abstract Background ASCQ-Me®, Neuro-QoL™, NIH Toolbox®, and PROMIS®, which are health-related quality of life measures collectively known as HealthMeasures, have experienced rapid uptake in the scientific community with over 1700 peer-reviewed publications through 2018. Because of their proliferation across multiple research disciplines, there has been significant heterogeneity in the description and reporting of these measures. Here, we provide a publication checklist to promote standardization and comparability across different reports. This checklist can be used across all HealthMeasures systems. Checklist Development: Authors drafted a draft checklist, circulated among the HealthMeasures Steering Committee and PROMIS Health Organization until the members reached consensus. Checklist: The final checklist has 21 entries in 4 categories: measure details, administration, scoring, and reporting. Most entries (11) specify necessary measure-specific details including version number and administration language(s). Administration (4 entries) reminds authors to include details such as use of proxy respondents and the assessment platform. Scoring (3 entries) is necessary to ensure replication and cross-study comparisons. Reporting (3 entries) reminds authors to always report scores on the T-score metric. Conclusion Consistent documentation is necessary to ensure transparent and reproducible methods and support the accumulation of evidence across studies. This checklist promotes standardization and completeness in documentation for ASCQ-Me, Neuro-QoL, PROMIS, and NIH Toolbox measures.

Over fifty years have passed since the last large scale longitudinal study of individuals with PAH deficiency in the U.S. Since then, there have been significant changes in terms of treatment recommendations as well as treatment options. The Phenylalanine Families and Researchers Exploring Evidence (PHEFREE) Consortium was recently established to collect a more up-to-date and extensive longitudinal natural history in individuals with phenylketonuria across the lifespan. In the present paper, we describe the structure and methods of the PHEFREE longitudinal study protocol and report cross-sectional data from an initial sample of 73 individuals (5 months to 54 years of age) with PAH deficiency who have enrolled. Looking forward, the study holds the promise for advancing the field on several fronts including the validation of novel neurocognitive tools for assessment in individuals with PKU as well as evaluation of the long-term effects of changes in metabolic control (e.g., effects of Phe-lowering therapies) on outcome., Competing Interests: Declaration of competing interest SEC has received consulting fees from BioMarin, Jnana, and PTC; and BioMarin has funded past and current research. GA has served as a consultant for PTC Therapeutics. DKG has conducted clinical research trials for BioMarin and Synlogic related to the treatment of PAH deficiency. COH has received consulting fees from BioMarin, Jnana Therapeutics, PTC Therapeutics, Sanofi, Pfizer, Synlogic, Tessera Therapeutics, and Tome Biosciences and conducted clinical research trials for BioMarin, Jnana Therapeutics, Sanofi, and Synlogic related to treatment of PAH deficiency. EJ has served as a consultant for Jnana Therapeutics, Arcturus Therapeutics, Travere Therapeutics, and participated in advisory boards for Jnana Therapeutics and Sanofi. HL has received consulting fees from BioMarin, Sanofi, Jnana, PTC, and Tome Biosciences. NL has served on advisory boards for Amgen/Horizon, Amicus Therapeutics, Audentes/Astrellas, BioMarin, Chiesi/Protalix, Sanofi, Ipsen, Jaguar Gene Therapy, Jnana, Leadiant Biosciences, Moderna, Nestlé Pharma, PTC Therapeutics, Reneo, and Ultragenyx and has received clinical trial support from Amgen/Horizon, Amicus Therapeutics, Audentes/Astrellas, BioMarin, Chiesi/Protalix, Sanofi, Jnana, Moderna, PTC Therapeutics, Takeda, and Ultragenyx. SS has served on advisory boards and received clinical trial support from BioMarin, Synlogic, PTC Therapeutics, and Jnana Therapeutics. JT has served as a consultant for BioMarin and has received clinical trials support from PTC Therapeutics, BioMarin, and Sanofi. DAW has received clinical trial support from BioMarin., (Copyright © 2024. Published by Elsevier Inc.)

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.

Objective: Low scores on neuropsychological tests are considered objective evidence of mild cognitive impairment. In clinical practice and research, it can be challenging to identify a cognitive deficit or mild cognitive impairment in high-functioning people because they are much less likely to obtain low test scores. This study was designed to improve the methodology for identifying mild cognitive impairment in adults who have above average or superior intellectual abilities. Method: Participants completed the National Institutes of Health Toolbox for the Assessment of Neurological and Behavioral Function Cognition Battery (NIHTB-CB). The sample included 384 adults between the ages of 20 and 85 who had completed either a 4-year college degree or who scored in the above average, superior, or very superior range on a measure of intellectual functioning, the Crystallized Composite score. Algorithms were developed, based on the absence of high scores and the presence of low scores, for identifying mild cognitive impairment. Results: Base rate tables for the presence of low scores and the absence of high scores are provided. The base rate for people with high average crystalized ability obtaining any one of the following, 5 scores <63rd percentile, or 4+ scores <50th percentile, or 3+ scores ≤ 25th percentile, or 2+ scores ≤ 16th percentile, is 15.5%. Conclusions: Algorithms were developed for identifying cognitive weakness or impairment in high-functioning people. Research is needed to test them in clinical groups, and to assess their association with clinical risk factors for cognitive decline and biomarkers of acquired neurological or neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background and objectivesThe NIH Toolbox for Neurological and Behavioral Function assessment battery contains measures in the domains of cognitive function, motor function, sensory function, and emotional health. It was designed for use in epidemiological and clinical trials health-related research.DesignThis paper describes the first phase of instrument development for the stress and self-efficacy subdomain of emotional health. Based on an extensive literature review and expert consultation, 127 measures were initially considered for inclusion in this subdomain, including measures of stress, self-efficacy, emotion regulation, and coping.ResultsSeveral measures, including emotion regulation and measures of coping strategies, did not meet criteria that were a priori established for inclusion. Psychometric properties of the remaining candidate measures were evaluated using data from five independent samples (combined N = 3175). Confirmatory and exploratory factor analyses indicated the Perceived Stress Scale and the General Self-Efficacy Scale each assessed single dimensions.ConclusionsBased on their psychometric performance, these two instruments were selected for inclusion and subsequent national norming for the NIH Toolbox.

Objective: Low scores on neuropsychological tests are considered objective evidence of mild cognitive impairment. In clinical practice and research, it can be challenging to identify a cognitive deficit or mild cognitive impairment in high-functioning people because they are much less likely to obtain low test scores. This study was designed to improve the methodology for identifying mild cognitive impairment in adults who have above average or superior intellectual abilities.Method: Participants completed the National Institutes of Health Toolbox for the Assessment of Neurological and Behavioral Function Cognition Battery (NIHTB-CB). The sample included 384 adults between the ages of 20 and 85 who had completed either a 4-year college degree or who scored in the above average, superior, or very superior range on a measure of intellectual functioning, the Crystallized Composite score. Algorithms were developed, based on the absence of high scores and the presence of low scores, for identifying mild cognitive impairment.Results: Base rate tables for the presence of low scores and the absence of high scores are provided. The base rate for people with high average crystalized ability obtaining any one of the following, 5 scores

Frontal lobe structures decline faster than most other brain regions in older adults. Age-related change in the frontal lobe is associated with poorer executive function (e.g., working memory, switching/set-shifting, and inhibitory control). The effects and presence of frontal lobe white matter hyperintensities (WMH) on executive function in normal aging is relatively unknown. The current study assessed relationships between region-specific frontal WMH load and cognitive performance in healthy older adults using three executive function tasks from the NIH Toolbox (NIHTB) Cognition Battery. A cohort of 279 healthy older adults ages 65–88 completed NIHTB and 3T T1-weighted and FLAIR MRI. Lesion Segmentation Toolbox quantified WMH volume and generated lesion probability maps. Individual lesion maps were registered to the Desikan-Killiany atlas in FreeSurfer 6.0 to define regions of interest (ROI). Independent linear regressions assessed relationships between executive function performance and region-specific WMH in frontal lobe ROIs. All models included age, sex, education, estimated total intracranial volume, multi-site scanner differences, and cardiovascular disease risk using Framingham criteria as covariates. Poorer set-shifting performance was associated with greater WMH load in three frontal ROIs including bilateral superior frontal (left β = −0.18, FDR-p = 0.02; right β = −0.20, FDR-p = 0.01) and right medial orbitofrontal (β = −0.17, FDR-p = 0.02). Poorer inhibitory performance associated with higher WMH load in one frontal ROI, the right superior frontal (right β = −0.21, FDR-p = 0.01). There were no significant associations between working memory and WMH in frontal ROIs. Our study demonstrates that location and pattern of frontal WMH may be important to assess when examining age-related differences in cognitive functions involving switching/set-shifting and inhibition. On the other hand, working memory performance was not related to presence of frontal WMH in this sample. These data suggest that WMH may contribute selectively to age-related declines in executive function. Findings emerged beyond predictors known to be associated with WMH presence, including age and cardiovascular disease risk. The spread of WMH within the frontal lobes may play a key role in the neuropsychological profile of cognitive aging. Further research should explore whether early intervention on modifiable vascular factors or cognitive interventions targeted for executive abilities may help mitigate the effect of frontal WMH on executive function.

Variability in working memory (WM) task selection likely contributes to heterogeneity in effect size estimates of deficiencies in youth with attention-deficit/hyperactivity disorder (ADHD). This has resulted in the development of brief, easy to administer assessments such as the NIH List Sorting Working Memory (LSWM) task from the NIH Cognitive Toolbox in hopes of standardizing measurement of this construct. Unfortunately, substantial questions persist regarding the specific constructs being evaluated by this task (e.g., visuospatial [VS] or phonological [PH] WM) as well as the ability of this task to detect WM deficits in previously identified impaired groups (e.g., ADHD). The current study examines the extent to which the LSWM task is associated with VS and PHWM performance as well as symptoms of ADHD. Additionally, we examined the magnitude of differences between ADHD and Typically Developing (TD) youth on this task relative to empirically derived WM tasks utilized in the past. Forty-six children (25 ADHD, 21 TD) completed multiple WM tasks. The LSWM task was moderately associated with PHWM and demonstrated relatively weaker associations with VSWM. Symptoms of inattention and hyperactivity/impulsivity were unrelated to the LSWM task; whereas tasks assessing PH and VSWM were moderately associated with inattention and weakly associated with hyperactivity (VSWM only). No significant between-group differences in performance emerged on the LSWM task; however, significant large-magnitude group differences were observed on both the PH and VSWM tasks. These findings suggest that the LSWM task may lack the ability to detect WM difficulties in youth with ADHD. [ABSTRACT FROM AUTHOR]

Frontal lobe structures decline faster than most other brain regions in older adults. Age-related change in the frontal lobe is associated with poorer executive function (e.g., working memory, switching/set-shifting, and inhibitory control). The effects and presence of frontal lobe white matter hyperintensities (WMH) on executive function in normal aging is relatively unknown. The current study assessed relationships between region-specific frontal WMH load and cognitive performance in healthy older adults using three executive function tasks from the NIH Toolbox (NIHTB) Cognition Battery. A cohort of 279 healthy older adults ages 65–88 completed NIHTB and 3T T1-weighted and FLAIR MRI. Lesion Segmentation Toolbox quantified WMH volume and generated lesion probability maps. Individual lesion maps were registered to the Desikan-Killiany atlas in FreeSurfer 6.0 to define regions of interest (ROI). Independent linear regressions assessed relationships between executive function performance and region-specific WMH in frontal lobe ROIs. All models included age, sex, education, estimated total intracranial volume, multi-site scanner differences, and cardiovascular disease risk using Framingham criteria as covariates. Poorer set-shifting performance was associated with greater WMH load in three frontal ROIs including bilateral superior frontal (left β = −0.18, FDR- p = 0.02; right β = −0.20, FDR- p = 0.01) and right medial orbitofrontal (β = −0.17, FDR- p = 0.02). Poorer inhibitory performance associated with higher WMH load in one frontal ROI, the right superior frontal (right β = −0.21, FDR- p = 0.01). There were no significant associations between working memory and WMH in frontal ROIs. Our study demonstrates that location and pattern of frontal WMH may be important to assess when examining age-related differences in cognitive functions involving switching/set-shifting and inhibition. On the other hand, working memory performance was not related to presence of frontal WMH in this sample. These data suggest that WMH may contribute selectively to age-related declines in executive function. Findings emerged beyond predictors known to be associated with WMH presence, including age and cardiovascular disease risk. The spread of WMH within the frontal lobes may play a key role in the neuropsychological profile of cognitive aging. Further research should explore whether early intervention on modifiable vascular factors or cognitive interventions targeted for executive abilities may help mitigate the effect of frontal WMH on executive function. [ABSTRACT FROM AUTHOR]

Introduction: The opiate epidemic has severe medical and social consequences. Opioids are commonly prescribed in patients with chronic pain, and are a main contributor to the opiate epidemic. The adverse effects of long-term opioid usage have been studied primarily in dependence/addiction disorders, but not in chronic pain. Here, we examine the added iatrogenic effects, psychology, and brain morphology of long-term opioid use in matched patients with chronic pain with and without opioid use (case–controlled design). Methods: We compared psychosocial, functional, and psychological measures between patients with chronic back pain (CBP) who were managing their pain with or without opioids, thereby controlling for the effect of pain on these outcomes. In addition, we investigated brain morphological differences associated with long-term opioid usage. We recruited 58 patients with CBP, 29 of them on long-term opioids and 29 who did not use opioids, and who were matched in terms of age, sex, pain intensity, and pain duration. Questionnaires were used to assess pain quality, pain psychology, negative and positive emotions, physical, cognitive, sensory, and motor functions, quality of life, and personality traits. Results: Patients with CBP on opioids displayed more negative emotion, poorer physical function, and more pain interference (p < 0.001), whereas there were no statistical differences in cognitive and motor functions and personality traits. Voxel-based morphometry using structural brain imaging data identified decreased gray matter density of the dorsal paracingulate cortex (family-wise error-corrected p < 0.05) in patients with opioids, which was associated with negative emotion (p = 0.03). Finally, a volumetric analysis of hippocampal subfields identified lower volume of the left presubiculum in patients on opioids (p < 0.001). Conclusion: Long-term opioid use in chronic pain is associated with adverse negative emotion and disabilities, as well as decreased gray matter volumes of specific brain regions. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the latent factor structure of the NIH Toolbox Cognition Battery (NIHTB-CB) and its measurement invariance across clinical diagnosis and key demographic variables including sex, race/ethnicity, age, and education for a typical Alzheimer's disease (AD) research sample. Method: The NIHTB-CB iPad English version, consisting of 7 tests, was administered to 411 participants aged 45–94 with clinical diagnosis of cognitively unimpaired, dementia, mild cognitive impairment (MCI), or impaired not MCI. The factor structure of the whole sample was first examined with exploratory factor analysis (EFA) and further refined using confirmatory factor analysis (CFA). Two groups were classified for each variable (diagnosis or demographic factors). The confirmed factor model was next tested for each group with CFA. If the factor structure was the same between the groups, measurement invariance was then tested using a hierarchical series of nested two-group CFA models. Results: A two-factor model capturing fluid cognition (executive function, processing speed, and memory) versus crystalized cognition (language) fit well for the whole sample and each group except for those with age < 65. This model generally had measurement invariance across sex, race/ethnicity, and education, and partial invariance across diagnosis. For individuals with age < 65, the language factor remained intact while the fluid cognition was separated into two factors: (1) executive function/processing speed and (2) memory. Conclusions: The findings mostly supported the utility of the battery in AD research, yet revealed challenges in measuring memory for AD participants and longitudinal change in fluid cognition. [ABSTRACT FROM AUTHOR]

• Two NIH Toolbox tasks demonstrate concurrent validity with existing neuropsychological measures. • Antiseizure medications and seizure onset age are associated with task performance. • Pilot data show good repeatability and the ability to show change over time. The NIH Toolbox Cognition Battery (NIHTB-CB) is designed to assess cognitive functioning across the lifespan. We aimed to evaluate the clinical validity of two NIHTB-CB tasks as cognitive screening tools in pediatric epilepsy by comparing them to standard neuropsychological measures and their association with epilepsy characteristics. Forty-seven patients with epilepsy ages 5–18, including ten repeat evaluations, were assessed. Correlational analyses and agreement statistics were conducted to validate NIHTB-CB tasks (Flanker Inhibitory Control and Attention test (Flanker) and Pattern Comparison Processing Speed test (Pattern Comparison)) with standard clinical measures. We also examined if performance was related to epilepsy characteristics, including polytherapy, age of seizure onset, seizure type, and history of Electrical Status Epilepticus in Sleep (ESES). The NIHTB-CB tests had moderate to strong correlations with neuropsychological measures of executive functioning, processing speed, and intelligence. Agreement statistics indicated better sensitivity than specificity. Polytherapy and later age of seizure onset were associated with lower performance on Pattern Comparison. ESES patients did not significantly differ in performance on the tests compared to non-ESES patients. Pilot data from a subset of repeated measures indicated a good range of change scores. These two NIHTB tasks are feasible as a screening tool in a clinic given their correlation with clinical measures that assess executive function, processing speed, and IQ. This study supports the use of these tasks as brief, easily accessible screener tools to identify cognitive dysfunction in domains commonly impacted in patients with epilepsy and potential use for monitoring over time. [ABSTRACT FROM AUTHOR]

Episodic memory is one of the most important cognitive domains that involves acquiring, storing and recalling new information. In this article, we describe a new measure developed for the NIH Toolbox, called the Picture Sequence Memory Test (PSMT) that is the first to examine episodic memory across the age range from 3 to 85. We describe the development of the measure and present validation data for ages 20 to 85. The PSMT involves presentation of sequences of pictured objects and activities in a fixed order on a computer screen and simultaneously verbally described, that the participant must remember and then reproduce over three learning trials. The results indicate good test-retest reliability and construct validity. Performance is strongly related to well-established "gold standard" measures of episodic memory and, as expected, much less well correlated with those of a measure of vocabulary. It shows clear decline with aging in parallel with a gold standard summary measure and relates to several other demographic factors and to self-reported general health status. The PSMT appears to be a reliable and valid test of episodic memory for adults, a finding similar to those found for the same measure with children.

PurposeTo develop a vision-targeted health-related quality of life (HRQOL) measure for the NIH Toolbox for the Assessment of Neurological and Behavioral Function.MethodsWe conducted a review of existing vision-targeted HRQOL surveys and identified color vision, low luminance vision, distance vision, general vision, near vision, ocular symptoms, psychosocial well-being, and role performance domains. Items in existing survey instruments were sorted into these domains. We selected non-redundant items and revised them to improve clarity and to limit the number of different response options. We conducted 10 cognitive interviews to evaluate the items. Finally, we revised the items and administered them to 819 individuals to calibrate the items and estimate the measure's reliability and validity.ResultsThe field test provided support for the 53-item vision-targeted HRQOL measure encompassing 6 domains: color vision, distance vision, near vision, ocular symptoms, psychosocial well-being, and role performance. The domain scores had high levels of reliability (coefficient alphas ranged from 0.848 to 0.940). Validity was supported by high correlations between National Eye Institute Visual Function Questionnaire scales and the new-vision-targeted scales (highest values were 0.771 between psychosocial well-being and mental health, and 0.729 between role performance and role difficulties), and by lower mean scores in those groups self-reporting eye disease (F statistic with p

The psychometric properties of the English-language NIH Toolbox for Assessment of Neurological and Behavioral Function (NIH Toolbox) have been examined in numerous populations. This study evaluated the reliability and validity of the Spanish-language NIH Toolbox. Participants were children aged 3 to 7 years and adults aged 18 to 85 years who took part in the NIH Toolbox norming study in Spanish. Results supported the internal consistency reliability of included measures. Test–retest reliability was strong for most tests, though it was weaker for the test of olfaction among children and the test of locomotion among adults. Spearman's correlations and general linear models showed Spanish tests were often associated with age, sex, and education. Convergent validity for the two language measures that underwent more intensive development, evaluated via Spearman's correlations with legacy measures, was strong. Results support using the Spanish-language NIH Toolbox to measure neurological and behavioral functioning among Spanish-speaking individuals in the United States. [ABSTRACT FROM AUTHOR]

Objectives: Head impact exposure (HIE) in youth football is a public health concern. The objective of this study was to determine if one season of HIE in youth football was related to cognitive changes. Method: Over 200 participants (ages 9–13) wore instrumented helmets for practices and games to measure the amount of HIE sustained over one season. Pre- and post-season neuropsychological tests were completed. Test score changes were calculated adjusting for practice effects and regression to the mean and used as the dependent variables. Regression models were calculated with HIE variables predicting neuropsychological test score changes. Results: For the full sample, a small effect was found with season average rotational values predicting changes in list-learning such that HIE was related to negative score change: standardized beta (β) = -.147, t(205) = -2.12, and p =.035. When analyzed by age clusters (9–10, 11–13) and adding participant weight to models, the R2 values increased. Splitting groups by weight (median split), found heavier members of the 9–10 cohort with significantly greater change than lighter members. Additionaly, significantly more participants had clinically meaningful negative changes: X2 = 10.343, p =.001. Conclusion: These findings suggest that in the 9–10 age cluster, the average seasonal level of HIE had inverse, negative relationships with cognitive change over one season that was not found in the older group. The mediation effects of age and weight have not been explored previously and appear to contribute to the effects of HIE on cognition in youth football players. [ABSTRACT FROM AUTHOR]

The judgement of human ability is ubiquitous, from school admissions to job performance reviews. The exact make-up of ability traits, however, is often narrowly defined and lacks a comprehensive basis. We attempt to simplify the spectrum of human ability, similar to how five personality traits are widely believed to describe most personalities. Finding such a basis for human ability would be invaluable since neuropsychiatric disease diagnoses and symptom severity are commonly related to such differences in performance. Here, we identified four underlying ability traits within the National Institutes of Health Toolbox normative data (n = 1, 369): (1) Motor-endurance, (2) Emotional processing, (3) Executive and cognitive function, and (4) Social interaction. We used the Human Connectome Project young adult dataset (n = 778) to show that Motor-endurance and Executive and cognitive function were reliably associated with specific brain functional networks (r2 = 0.305 ± 0.021), and the biological nature of these ability traits was also shown by calculating their heritability (31 and 49%, respectively) from twin data.

Objective: The association between hippocampal volume and memory is continuing to be characterized in healthy older adults. Prior research suggests smaller hippocampal volume in healthy older adults is associated with poorer episodic memory and processing speed, as well as working memory, verbal learning, and executive functioning as measured by the NIH Toolbox Fluid (Fluid Cognition Composite, FCC) and Crystalized Cognition Composites (CCC). This study aimed to replicate these findings and to evaluate the association between: (1) hippocampal asymmetry index and cognition; and (2) independent contributions of the left and right hippocampal volume and cognition in a large sample of healthy older adults.Participants and Methods: One-hundred and eighty-three healthy older adults (M age = 71.72, SD = 5.3) received a T1-weighted sequence on a 3T scanner. Hippocampal subfields were extracted using FreeSurfer 6.0 and combined to provide left, right, and total hippocampal volumes. FCC subtests include Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, List Sorting, Picture Sequence Memory, and Pattern Comparison. CCC subtests include Picture Vocabulary and Oral Reading Recognition. Multiple linear regressions were performed predicting cognition composites from the total, left and right, and asymmetry of hippocampal volume, controlling for sex, education, scanner, and total intracranial volume. Multiple comparisons in primary analyses were corrected using a false discovery rate (FDR) of p < 0.05.Results: FCC scores were positively associated with total (β = 0.226, FDR q = 0.044) and left (β = 0.257, FDR q = 0.024) hippocampal volume. Within FCC, Picture Sequence Memory scores positively associated with total (β = 0.284, p = 0.001) and left (β = 0.98, p = 0.001) hippocampal volume. List Sorting scores were also positively associated with left hippocampal volume (β = 0.189, p = 0.029).Conclusions: These results confirm previous research suggesting that bilateral hippocampal volume is associated with FCC, namely episodic memory. The present study also suggests the left hippocampal volume may be more broadly associated with both episodic and working memory. Studies should continue to investigate lateralized hippocampal contributions to aging processes to better identify predictors of cognitive decline.

A major goal of animal research is to identify interventions that can promote successful aging and delay or reverse age-related cognitive decline in humans. Recent advances in standardizing cognitive assessment tools for humans have the potential to bring preclinical work closer to human research in aging and Alzheimer’s disease. The National Institute of Health (NIH) has led an initiative to develop a comprehensive Toolbox for Neurologic Behavioral Function (NIH Toolbox) to evaluate cognitive, motor, sensory and emotional function for use in epidemiologic and clinical studies spanning 3 to 85 years of age. This paper aims to analyze the strengths and limitations of animal behavioral tests that can be used to parallel those in the NIH Toolbox. We conclude that there are several paradigms available to define a preclinical battery that parallels the NIH Toolbox. We also suggest areas in which new tests may benefit the development of a comprehensive preclinical test battery for assessment of cognitive function in animal models of aging and Alzheimer’s disease.