Exploring symptom clusters in mild cognitive impairment and dementia with the NIH Toolbox.

OBJECTIVE: Symptom clustering research provides a unique opportunity for understanding complex medical conditions. The objective of this study was to apply a variable-centered analytic approach to understand how symptoms may cluster together, within and across domains of functioning in mild cognitive impairment (MCI) and dementia, to better understand these conditions and potential etiological, prevention, and intervention considerations. METHOD: Cognitive, motor, sensory, emotional, and social measures from the NIH Toolbox were analyzed using exploratory factor analysis (EFA) from a dataset of 165 individuals with a research diagnosis of either amnestic MCI or dementia of the Alzheimer's type. RESULTS: The six-factor EFA solution described here primarily replicated the intended structure of the NIH Toolbox with a few deviations, notably sensory and motor scores loading onto factors with measures of cognition, emotional, and social health. These findings suggest the presence of cross-domain symptom clusters in these populations. In particular, negative affect, stress, loneliness, and pain formed one unique symptom cluster that bridged the NIH Toolbox domains of physical, social, and emotional health. Olfaction and dexterity formed a second unique cluster with measures of executive functioning, working memory, episodic memory, and processing speed. A third novel cluster was detected for mobility, strength, and vision, which was considered to reflect a physical functioning factor. Somewhat unexpectedly, the hearing test included did not load strongly onto any factor. CONCLUSION: This research presents a preliminary effort to detect symptom clusters in amnestic MCI and dementia using an existing dataset of outcome measures from the NIH Toolbox.

Identifying Health-Related Quality of Life Domains After Upper Extremity Transplantation.

OBJECTIVE: To identify the most important health-related quality of life (HRQOL) domains and patient-reported outcomes after upper extremity transplantation (UET) in individuals with upper extremity amputation. DESIGN: Verbatim audio-recordings of individual interviews and focus groups were analyzed using qualitative, grounded theory-based methods to identify important domains of HRQOL and provide guidance for outcomes measurement after UET. SETTING: Individual interviews were conducted by phone. Focus groups were conducted at 5 upper extremity vascularized composite allotransplantation (VCA) centers in the US and at an international conference of VCA experts. PARTICIPANTS: Individual phone interviews were conducted with 5 individuals with lived experience of UET. Thirteen focus groups were conducted with a total of 59 clinical professionals involved in UET. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Not applicable. RESULTS: Twenty-eight key HRQOL domains were identified, including physical functioning and medical complications, positive and negative emotional functioning, and social participation, relations, and independence. We identified key constructs for use in evaluation of the potentially substantial physical, medical, social, and emotional effects of UET. CONCLUSIONS: This study provides an overview of the most important issues affecting HRQOL after UET, including several topics that are unique to individuals with UET. This information will be used to establish systematic, comprehensive, and longitudinal measurement of post-UET HRQOL outcomes.

5-Year Activity and Participation Outcomes of the First Successful Pediatric Bilateral Hand Transplantation: A Case Report.

AIMS: Describe the 5-year outcomes of the first successful pediatric bilateral hand transplantation. METHODS: The child underwent quadrimembral amputation at age two and received bilateral hand allografts at age eight. Rehabilitation included biomechanical, neurorehabilitation, and occupational approaches in acute and outpatient settings. Therapist observed outcomes, patient-reported measures, and parent-reported measures were repeated over a 5-year period. RESULTS: Observation assessments revealed functional dexterity skills and modified independence to full independence with self-care activities. The parent reported the child had moderate difficulty with upper extremity functioning 25-, 41-, and 48-months post-transplantation, and mild difficulty at 60-months; the child reported no difficulties in this domain at 41 months. Five years post-transplantation the child reported enjoying many age-appropriate activities, and high-quality peer relations were endorsed by both parent and child. CONCLUSION: The child developed hand movements for daily activities and was completing daily activities with improved efficiency. Health-related quality of life outcomes were favorable.

Responsiveness of the Traumatic Brain Injury Quality of Life Cognition Banks in Recent Brain Injury.

Patient report of functioning is one component of the neurocognitive exam following traumatic brain injury, and standardized patient-reported outcomes measures are useful to track outcomes during rehabilitation. The Traumatic Brain Injury Quality of Life measurement system (TBI-QOL) is a TBI-specific extension of the PROMIS and Neuro-QoL measurement systems that includes 20 item banks across physical, emotional, social, and cognitive domains. Previous research has evaluated the responsiveness of the TBI-QOL measures in community-dwelling individuals and found clinically important change over a 6-month assessment interval in a sample of individuals who were on average 5 years post-injury. In the present study, we report on the responsiveness of the TBI-QOL Cognition-General Concerns and Executive Function item bank scores and the Cognitive Health Composite scores in a recently injured sample over a 1-year study period. Data from 128 participants with complicated mild, moderate, or severe TBI within the previous 6 months were evaluated. The majority of the sample was male, white, and non-Hispanic. The participants were 18-92 years of age and were first evaluated from 0 to 5 months post-injury. Eighty participants completed the 1-year follow-up assessment. Results show acceptable standard response mean values (0.47-0.51) for all measures and minimal detectable change values ranging from 8.2 to 8.8 T-score points for Cognition-General Concerns and Executive Functioning measures. Anchor rating analysis revealed that changes in scores on the Executive Function item bank and the Cognitive Health Composite were meaningfully associated with participant-reported changes in the areas of attention, multitasking, and memory. Evaluation of change score differences by a variety of clinical indicators demonstrated a small but significant difference in the three TBI-QOL change scores by TBI injury severity grouping. These results support the responsiveness of the TBI-QOL cognition measures in newly injured individuals and provides information on the minimal important differences for the TBI-QOL cognition measures, which can be used for score interpretation by clinicians and researchers seeking patient-reported outcome measures of self-reported cognitive QOL after TBI.

Validation of the Spinal Cord Injury-Functional Index for Use in Community-Dwelling Individuals With SCI.

OBJECTIVE: To evaluate the psychometric properties of the Spinal Cord Injury-Functional Index (SCI-FI) instruments in a community-dwelling sample. DESIGN: Cross-sectional study. SETTING: Community setting. PARTICIPANTS: Individuals (N=269) recruited from 6 SCI Model Systems sites. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants completed computer adaptive test and short form versions of 4 SCI-FI/Capacity (C) banks (ie, Ambulation, Basic Mobility, Fine Motor, Self-Care) and 1 SCI-FI/Assistive Technology (AT) bank (Wheelchair Mobility) at baseline and after 2 weeks. The Self-Report Functional Measure (SRFM) and the clinician-rated motor FIM were used to evaluate evidence of convergent validity. RESULTS: Pearson correlations, intraclass correlation coefficients, minimal detectable change, and Bland-Altman plots supported the test-retest reliability of the SCI-FI instruments. Correlations were large with the SRFM (.69-.89) and moderate-to-large for the FIM instrument (.44-.64), supporting convergent validity. Known-groups validity was demonstrated by a significant main effect of injury level on all instruments and a main effect of injury completeness on the SCI-FI/C instruments. A ceiling effect was detected for individuals with incomplete paraplegia on the Fine Motor/C and Self-Care/C Short Forms. CONCLUSION: Findings support the test-retest reliability, convergent validity, and known-groups validity of the SCI-FI/C instruments and the SCI-FI/AT Wheelchair Mobility instruments for use by community-dwelling individuals.

Assessment of quality of life after upper extremity transplantation: Framework for patient-reported outcome scale domains.

Upper extremity transplantation offers the promise of restored function and regained quality of life (QOL) for individuals who have sustained hand or arm amputation. However, a major challenge for this procedure becoming an accessible treatment option for patients is the lack of standard measures to document benefits to QOL. Patient-reported outcomes (PRO) measures are well-suited for this kind of intervention, where the perspective of the patient is central to defining treatment success. To date, qualitative work with experts, clinicians, and patients has been used to identify the most important domains of QOL for PRO item development. Specifically, our group's qualitative work has identified several domains of QOL that are unique to individuals who have received upper extremity transplants, which are distinct from topics covered by existing PRO measures. These include emotional and social aspects of upper extremity transplant, such as Expectations and Perceived Outcomes, Integration and Assimilation of Transplant, Fitting in, and Post-Surgical Challenges and Complications. The broad topic of Satisfaction with Transplant was subdivided into three subtopics: Function, Sensation, and Aesthetics. Satisfaction with Sensation was also identified as a unique domain not evaluated by existing PRO measures. This report operationalizes these eight QOL domains by presenting scoping definitions. This manuscript describes the work that has been completed for domain characterization as an early step toward developing standardized PRO measures to evaluate these important outcomes specific to upper extremity transplantation.

Development of Composite Scores for the TBI-QOL.

OBJECTIVE: To develop a set of composite scores that can be used for interpreting quality of life (QOL) after traumatic brain injury (TBI) using 9 of the patient-reported outcomes measures from the Traumatic Brain Injury Quality of Life (TBI-QOL) measurement system. DESIGN: Participants completed 20 item banks from the TBI-QOL as part of a larger assessment. Composite index scores were created with normalized transformation with nonlinear area conversion using scores from 9 of the banks, and are expressed in index score units, with higher composite scores indicating better functioning. For descriptive purposes, associations among composites and individual banks were evaluated using regression, along with patterns of composite scores by injury severity groups using analysis of variance. SETTING: Three medical centers in the United States. PARTICIPANTS: Community-dwelling adults (n=504) with a history of TBI. INTERVENTIONS: Not applicable. MAIN OUTCOMES MEASURE: TBI-QOL. RESULTS: Five composite indices were generated: global QOL, physical health, emotional health, cognitive health, and social health. Lookup tables are provided herein. Composite scores were highly intercorrelated (all r>.60, P<.0001), and individual TBI-QOL banks all correlate strongly with the global QOL composite in the expected direction (all r>.50, P<.0001). CONCLUSION: Researchers and clinicians can use the TBI-QOL global QOL, physical health, emotional health, cognitive health, and social health composite scores to aggregate results from multiple TBI-QOL banks, which is anticipated to ease interpretation and reliability. This work additionally highlights the importance of considering nonphysical symptoms as outcomes variables for TBI research, as cognitive, social, and emotional domains were some of the most strongly correlated banks with the global QOL composite.

Measuring Self-Reported Cognitive Function Following TBI: Development of the TBI-QOL Executive Function and Cognition-General Concerns Item Banks.

OBJECTIVE: To develop and calibrate new patient-reported outcome measures of cognitive concerns for individuals with traumatic brain injury (TBI). SETTING: Five TBI model systems rehabilitation centers in the United States. PARTICIPANTS: Adults with medically confirmed history of TBI. DESIGN: Cross-sectional survey in interview format. MAIN MEASURES: Traumatic Brain Injury-Quality of Life (TBI-QOL) Executive Function and TBI-QOL Cognition-General Concerns item banks. RESULTS: A total of 569 adults with complicated-mild, moderate, or severe TBI completed preliminary item pools, which included 65 Executive Function items and 56 Cognition-General Concerns items. Confirmatory factor analysis supported the retention of 37 Executive Function and 39 Cognition-General Concerns items. Samejima's graded response model was used to estimate item parameters for associated computer adaptive test administrations, and informed the selection of corresponding static short forms. Data from an independent sample of 77 adults with complicated-mild, moderate, or severe TBI supported the test-retest reliability of these newly developed measures. CONCLUSION: The TBI-QOL Executive Function and Cognition-General Concerns item banks provide researchers and clinicians with reliable tools for assessing patient-reported post-TBI cognitive difficulties as part of the comprehensive TBI-QOL measurement system.

Development of the TBI-QOL Headache Pain Item Bank and Short Form.

OBJECTIVE: To develop, calibrate, and evaluate the test-retest reliability of a new patient-reported outcome measure of headache pain relevant for individuals with traumatic brain injury (TBI). SETTING: Six TBI Model Systems rehabilitation centers in the United States. PARTICIPANTS: Adults with medically confirmed documentation of TBI. DESIGN: Cross-sectional calibration field testing and test-retest reliability analyses. MAIN MEASURES: Traumatic Brain Injury-Quality of Life Headache Pain item bank. RESULTS: Thirteen headache pain items were calibrated as a unidimensional measure using data from 590 participants. The new measure was reliable (α = .98; item-total correlation range: 0.71-0.91). Item parameter estimates were estimated using Samejima's Graded Response Model and a 10-item calibrated short form was created. Simulation testing confirmed that both the computer-adaptive test and the short-form administrations were equivalent to the full item bank. One- to-2-week test-retest reliability of the computer-adaptive test was high (Pearson r and intraclass correlation coefficients = 0.81). Approximately two-thirds of the sample reported at least 1 headache symptom. CONCLUSION: The Traumatic Brain Injury-Quality of Life Headache Pain item bank and short form provide researchers and clinicians with reliable measures of the subjective experience of headache symptoms for individuals with a history of TBI.

Linking the GAD-7 and PHQ-9 to the TBI-QOL Anxiety and Depression Item Banks.

OBJECTIVE: To link scores on commonly used measures of anxiety (7-item Generalized Anxiety Disorder Scale; GAD-7) and depression (9-item Patient Health Questionnaire; PHQ-9) to the Traumatic Brain Injury Quality of Life (TBI-QOL) measurement system. SETTING: 5 Traumatic Brain Injury Model Systems. PARTICIPANTS: A total of 385 individuals with traumatic brain injury (TBI) (31% complicated mild; 14% moderate; and 54% severe). DESIGN: Observational cohort. MAIN MEASURES: GAD-7, PHQ-9, TBI-QOL Anxiety v1.0 and TBI-QOL Depression v1.0. RESULTS: Item response theory-based linking methods were used to create crosswalk tables that convert scores on the GAD-7 to the TBI-QOL Anxiety metric and scores on the PHQ-9 to the TBI-QOL Depression metric. Comparisons between actual and crosswalked scores suggest that the linkages were successful and are appropriate for group-level analysis. Linking functions closely mirror crosswalks between the GAD-7/PHQ-9 and the Patient-Reported Outcomes Measurement Information System (PROMIS), suggesting that general population linkages are similar to those from a TBI sample. CONCLUSION: Researchers and clinicians can use the crosswalk tables to transform scores on the GAD-7 and the PHQ-9 to the TBI-QOL metric for group-level analyses.

Nih toolbox premorbid ability adjustments: Application in a traumatic brain injury sample.

PURPOSE/OBJECTIVE: Metrics to estimate premorbid cognitive ability, such as word reading tests, are important for clinical determination of cognitive changes following brain injury. In the present study, reading adjusted scores for the National Institutes of Health Toolbox Cognition Battery (NIHTB-CB) fluid tests were developed and validated with a sample of individuals with traumatic brain injury (TBI), to evaluate the clinical utility of reading-adjusted scores. Research Method/Design: The development sample included 843 adult participants, ages 20-85, from the NIHTB-CB standardization sample. A sample of 158 participants with complicated mild or moderate TBI (n = 74) or severe TBI (n = 84) were administered the NIHTB-CB, and comprised the validation sample. Scores were derived for the five fluid tests using four adjustment models: age-only, demographic-only, age-and-reading, and demographic-and-reading referenced scores. RESULTS: Estimated premorbid ability varies depending on the reference model. Scores from each of the four reference models differentiated the comparison and TBI samples at the group level. However, performance varied by premorbid ability. CONCLUSIONS/IMPLICATIONS: Premorbid ability affects identification of cognitive difficulties after TBI. Reading referenced scores provide an individualized estimate of the effects of premorbid ability than demographic characteristics alone. Each model identified a similar number of individuals as having cognitive difficulties; however, the models differed on which individuals had cognitive difficulties. The models had higher disagreement rates in the clinical compared with the comparison sample, particularly for individuals with lower premorbid ability. Clinical use and caveats are discussed. (PsycINFO Database Record

Bilateral basal ganglia activity in verbal working memory.

Although the cortical substrates of verbal working memory are reasonably well understood, less is known about the relative contribution of subcortical structures to verbal working memory. Therefore, in addition to elaboration of a model of verbal working memory by including a specific focus on basal ganglia, the purpose of this study also was to examine potential differences in neural function across the complete process of verbal working memory, from encoding through retrieval. Functional magnetic resonance imaging was used to observe regions of brain activation in neurologically normal participants during a task of verbal working memory. The expected frontal-parietal network was found to be active over the course of the verbal working memory task. The encoding portion of the task engaged left inferior frontal regions and bilateral caudate and thalamus. Bilateral medial thalamus and posterior cingulate regions were engaged during the maintenance phase of the task. Retrieval activated the left inferior frontal sulcus and posterior parietal/occipital regions. Findings are considered in light of current models of verbal working memory and subcortical structures.

Cognitive predictors of verbal memory in a mixed clinical pediatric sample.

Verbal memory problems, along with other cognitive difficulties, are common in children diagnosed with neurological and/or psychological disorders. Historically, these "memory problems" have been poorly characterized and often present with a heterogeneous pattern of performance across memory processes, even within a specific diagnostic group. The current study examined archival neuropsychological data from a large mixed clinical pediatric sample in order to understand whether functioning in other cognitive areas (i.e., verbal knowledge, attention, working memory, executive functioning) may explain some of the performance variability seen across verbal memory tasks of the Children's Memory Scale (CMS). Multivariate analyses revealed that among the cognitive functions examined, only verbal knowledge explained a significant amount of variance in overall verbal memory performance. Further univariate analyses examining the component processes of verbal memory indicated that verbal knowledge is specifically related to encoding, but not the retention or retrieval stages. Future research is needed to replicate these findings in other clinical samples, to examine whether verbal knowledge predicts performance on other verbal memory tasks and to explore whether these findings also hold true for visual memory tasks. Successful replication of the current study findings would indicate that interventions targeting verbal encoding deficits should include efforts to improve verbal knowledge.