Associations between NIH Toolbox Cognition Battery and in vivo brain amyloid and tau pathology in non-demented older adults.
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ABSTRACT:
SUBMITTER: Snitz BE
PROVIDER: S-EPMC7228102 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Associations between NIH Toolbox Cognition Battery and <i>in vivo</i> brain amyloid and tau pathology in non-demented older adults.
Snitz Beth E BE Tudorascu Dana L DL Yu Zheming Z Campbell Elizabeth E Lopresti Brian J BJ Laymon Charles M CM Minhas Davneet S DS Nadkarni Neelesh K NK Aizenstein Howard J HJ Klunk William E WE Weintraub Sandra S Gershon Richard C RC Cohen Ann D AD
Alzheimer's & dementia (Amsterdam, Netherlands) 20200515 1
<h4>Introduction</h4>The National Institutes of Health (NIH) Toolbox Cognition Battery (NIHTB-CB) was developed to be a common assessment metric across a broad array of research studies. We investigated associations between NIHTB-CB and brain amyloid and tau deposition in cognitively unimpaired older adults.<h4>Methods</h4>One hundred eighteen community-based volunteers completed magnetic resonance imaging (MRI), Pittsburgh compound B (PiB)-PET (positron emission tomography) and AV-1451-PET neur ...[more]
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Project description:Demographic factors impact neuropsychological test performances and accounting for them may help to better elucidate current brain functioning. The NIH Toolbox Cognition Battery (NIHTB-CB) is a novel neuropsychological tool, yet the original norms developed for the battery did not adequately account for important demographic/cultural factors known to impact test performances. We developed norms fully adjusting for all demographic variables within each language group (English and Spanish) separately. The current study describes the standards for individuals tested in English. Neurologically healthy adults (n=1038) and children (n=2917) who completed the NIH Toolbox norming project in English were included. We created uncorrected scores weighted to the 2010 Census demographics, and applied polynomial regression models to develop age-corrected and fully demographically adjusted (age, education, sex, race/ethnicity) scores for each NIHTB-CB test and composite (i.e., Fluid, Crystallized, and Total Composites). On uncorrected NIHTB-CB scores, age and education demonstrated significant, medium-to-large associations, while sex showed smaller, but statistically significant effects. In terms of race/ethnicity, a significant stair-step effect on uncorrected NIHTB-CB scores was observed (African American<Hispanic<White). After applying normative corrections, NIHTB-CB no longer demonstrated any significant associations with demographic factors. The previously developed norms still maintained significant associations with demographic factors, and demonstrated more variable impairment rates in segments of the healthy normative sample. Similar to other neuropsychological tests, demographic factors demonstrated significant associations with unadjusted NIHTB-CB scores. Application of fully corrected scores will help account for unwanted variance that is associated with non-clinical factors to more accurately reflect effects of disease-related changes in brain function.
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Project description:OBJECTIVE:Few independent studies have examined the psychometric properties of the NIH Toolbox Cognition Battery (NIHTB-CB) in older adults, despite growing interest in its use for clinical purposes. In this paper we report the test-retest reliability and construct validity of the NIHTB-CB, as well as its agreement or concordance with traditional neuropsychological tests of the same construct to determine whether tests could be used interchangeably. METHODS:Sixty-one cognitively healthy adults ages 60-80 completed "gold standard" (GS) neuropsychological tests, NIHTB-CB, and brain MRI. Test-retest reliability, convergent/discriminant validity, and agreement statistics were calculated using Pearson's correlations, concordance correlation coefficients (CCC), and root mean square deviations. RESULTS:Test-retest reliability was acceptable (CCC = .73 Fluid; CCC = .85 Crystallized). The NIHTB-CB Fluid Composite correlated significantly with cerebral volumes (r's = |.35-.41|), and both composites correlated highly with their respective GS composites (r's = .58-.84), although this was more variable for individual tests. Absolute agreement was generally lower (CCC = .55 Fluid; CCC = .70 Crystallized) due to lower precision in fluid scores and systematic overestimation of crystallized composite scores on the NIHTB-CB. CONCLUSIONS:These results support the reliability and validity of the NIHTB-CB in healthy older adults and suggest that the fluid composite tests are at least as sensitive as standard neuropsychological tests to medial temporal atrophy and ventricular expansion. However, the NIHTB-CB may generate different estimates of performance and should not be treated as interchangeable with established neuropsychological tests.
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Project description:Hispanics are the fastest growing ethnicity in the United States, yet there are limited well-validated neuropsychological tools in Spanish, and an even greater paucity of normative standards representing this population. The Spanish NIH Toolbox Cognition Battery (NIHTB-CB) is a novel neurocognitive screener; however, the original norms were developed combining Spanish- and English-versions of the battery. We developed normative standards for the Spanish NIHTB-CB, fully adjusting for demographic variables and based entirely on a Spanish-speaking sample. A total of 408 Spanish-speaking neurologically healthy adults (ages 18-85 years) and 496 children (ages 3-7 years) completed the NIH Toolbox norming project. We developed three types of scores: uncorrected based on the entire Spanish-speaking cohort, age-corrected, and fully demographically corrected (age, education, sex) scores for each of the seven NIHTB-CB tests and three composites (Fluid, Crystallized, Total Composites). Corrected scores were developed using polynomial regression models. Demographic factors demonstrated medium-to-large effects on uncorrected NIHTB-CB scores in a pattern that differed from that observed on the English NIHTB-CB. For example, in Spanish-speaking adults, education was more strongly associated with Fluid scores, but showed the strongest association with Crystallized scores among English-speaking adults. Demographic factors were no longer associated with fully corrected scores. The original norms were not successful in eliminating demographic effects, overestimating children's performances, and underestimating adults' performances on the Spanish NIHTB-CB. The disparate pattern of demographic associations on the Spanish versus English NIHTB-CB supports the need for distinct normative standards developed separately for each population. Fully adjusted scores presented here will aid in more accurately characterizing acquired brain dysfunction among U.S. Spanish-speakers.
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Project description:ObjectiveThis 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.MethodThe 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.ResultsA 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.ConclusionsThe 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.
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Project description:BackgroundRecent advances in understanding molecular and synaptic mechanisms of intellectual disabilities (ID) in fragile X syndrome (FXS) and Down syndrome (DS) through animal models have led to targeted controlled trials with pharmacological agents designed to normalize these underlying mechanisms and improve clinical outcomes. However, several human clinical trials have failed to demonstrate efficacy of these targeted treatments to improve surrogate behavioral endpoints. Because the ultimate index of disease modification in these disorders is amelioration of ID, the validation of cognitive measures for tracking treatment response is essential. Here, we present preliminary research to validate the National Institutes of Health Toolbox Cognitive Battery (NIH-TCB) for ID.MethodsWe completed three pilot studies of patients with FXS (total n = 63; mean age 19.3 ± 8.3 years, mean mental age 5.3 ± 1.6 years), DS (n = 47; mean age 16.1 ± 6.2, mean mental age 5.4 ± 2.0), and idiopathic ID (IID; n = 16; mean age 16.1 ± 5.0, mean mental age 6.6 ± 2.3) measuring processing speed, executive function, episodic memory, word/letter reading, receptive vocabulary, and working memory using the web-based NIH-TB-CB, addressing feasibility, test-retest reliability, construct validity, ecological validity, and syndrome differences and profiles.ResultsFeasibility was good to excellent (≥80 % of participants with valid scores) for above mental age 4 years for all tests except list sorting (working memory). Test-retest stability was good to excellent, and convergent validity was similar to or better than results obtained from typically developing children in the normal sample for executive function and language measures. Examination of ecological validity revealed moderate to very strong correlations between the NIH-TCB composite and adaptive behavior and full-scale IQ measures. Syndrome/group comparisons demonstrated significant deficits for the FXS and DS groups relative to IID on attention and inhibitory control, a significant reading weakness for FXS, and a receptive vocabulary weakness for DS.ConclusionsThe NIH-TCB has potential for assessing important dimensions of cognition in persons with ID, and several tests may be useful for tracking response to intervention. However, more extensive psychometric studies, evaluation of the NIH-TCB's sensitivity to change, both developmentally and in the context of treatment, and perhaps establishing links to brain function in these populations, are required to determine the true utility of the battery as a set of outcome measures.
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Project description:Importance:Cognitive dysfunction (CD) is recognized by the American Cancer Society as a treatment effect in head and neck cancer, but the extent of this problem at baseline in oropharyngeal cancer (OPC), the most common subsite in current practice, to our knowledge has never been studied. Objective:To assess the baseline cognition of patients with OPC using National Institutes of Health (NIH)-sponsored instruments of Patient-Reported Outcomes Measurement Information System (PROMIS) and NIH Toolbox Cognitive Battery (NIHTB-CB). Design, Setting, and Participants:This was a prospective cohort study conducted at a tertiary academic center. Of 83 consecutive patients, newly diagnosed as having OPC from September 2016 to May 2017, 16 were ineligible, 8 refused to participate, and 3 were lost to follow-up after screening, resulting in 56 study participants. Main Outcomes and Measures:Self-perceived and objective cognition with PROMIS and NIHTB-CB standardized T scores, respectively, were main outcomes. Impairment was defined as (1) T scores less than 0.5 SD for PROMIS; (2) T score less than 1.5 SD in at least 1 cognitive domain or less than 1 SD in 2 or more domains for NIHTB-CB total cognition; and (3) T score per previously published criteria for NIHTB-CB intelligence-stratified cognition. Results:Of the 56 study participants (52 men, 4 women; median age, 59 years [range, 42-77 years]), 19 (34%) had a college degree, and 20 (36%) had a professional or technical occupation. Thirty (about 53%) were never-smokers, 26 (46%) were never-drinkers, 29 (52%) were obese, 13 (23%) had a moderate to severe comorbidity, 3 (5%) used antidepressants, and 25 (52%) had hearing loss. Impaired self-reported, NIHTB-CB total, and intelligence-stratified cognition scores were observed in 6 (11%), 18 (32%), and 12 (21%), respectively. Among all variables, objective impairment was more common in men (23% vs 0%) and those with p16-negative OPC (33% vs 20%), moderate to severe comorbidity (31% vs 18%), and hearing loss (31% vs 12%). Conclusions and Relevance:Impaired objective cognition was more common at baseline than self-reported, and was more frequent in men, participants with p16-negative OPC, moderate to severe comorbidity, and hearing loss. NIHTB-CB allowed immediate scoring of demographically adjusted cognitive function. In clinical practice, these scores can be used to identify patients with impaired cognition at baseline who may be susceptible to developing further impairment after treatment. Identification of impairment at baseline will help to institute early cognitive interventions, which may lead to an improved posttreatment quality of life.
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