The cognition battery of the NIH toolbox for assessment of neurological and behavioral function: validation in an adult sample.

This study introduces a special series on validity studies of the Cognition Battery (CB) from the U.S. National Institutes of Health Toolbox for the Assessment of Neurological and Behavioral Function (NIHTB) (Gershon, Wagster et al., 2013) in an adult sample. This first study in the series describes the sample, each of the seven instruments in the NIHTB-CB briefly, and the general approach to data analysis. Data are provided on test-retest reliability and practice effects, and raw scores (mean, standard deviation, range) are presented for each instrument and the gold standard instruments used to measure construct validity. Accompanying papers provide details on each instrument, including information about instrument development, psychometric properties, age and education effects on performance, and convergent and discriminant construct validity. One study in the series is devoted to a factor analysis of the NIHTB-CB in adults and another describes the psychometric properties of three composite scores derived from the individual measures representing fluid and crystallized abilities and their combination. The NIHTB-CB is designed to provide a brief, comprehensive, common set of measures to allow comparisons among disparate studies and to improve scientific communication.

I. NIH Toolbox Cognition Battery (CB): introduction and pediatric data.

This monograph presents the pediatric portion of the National Institutes of Health (NIH) Toolbox Cognition Battery (CB) of the NIH Toolbox for the Assessment of Neurological and Behavioral Function. The NIH Toolbox is an initiative of the Neuroscience Blueprint, a collaborative framework through which 16 NIH Institutes, Centers, and Offices jointly support neuroscience-related research, to accelerate discoveries and reduce the burden of nervous system disorders. The CB is one of four modules that measure cognitive, emotional, sensory, and motor health across the lifespan. The CB is unique in its continuity across childhood, adolescence, early adulthood, and old age, and in order to help create a common currency among disparate studies, it is also available at low cost to researchers for use in large-scale longitudinal and epidemiologic studies. This chapter describes the evolution of the CB; methods for selecting cognitive subdomains and instruments; the rationale for test design; and a validation study in children and adolescents, ages 3-15 years. Subsequent chapters feature detailed discussions of each test measure and its psychometric properties (Chapters 2-6), the factor structure of the test battery (Chapter 7), the effects of age and education on composite test scores (Chapter 8), and a final summary and discussion (Chapter 9). As the chapters in this monograph demonstrate, the CB has excellent psychometric properties, and the validation study provided evidence for the increasing differentiation of cognitive abilities with age.

Global occurrence of depressive symptoms during the COVID-19 pandemic.

OBJECTIVE: This study aimed to estimate the occurrence of depressive symptoms in a global population of young, middle-aged and older adults amid the COVID-19 pandemic. Study data also assessed the impact of the social restrictions caused by the pandemic on depressive symptomatology. METHODS: A self-administered internet-based survey was completed by 111,225 individuals residing in 176 countries (March-April 2020). We retained: demographic data, depressive symptoms (PHQ8), anxieties specific to the COVID-19, personality traits (Big-Five Personality Questionnaire), comorbidity frequency, health quality, behavioral variables (i,e., staying at home, avoiding social gatherings, social distancing in the past week). Occurrence of depressive symptoms was estimated using standard cut-offs (total PHQ8 score ≥ 10). Hierarchical regression modeling examined correlates of depressive symptoms (PHQ8 score) in three groups stratified by age, i.e., 18-34, 35-54 and 55+ years. RESULTS: Moderate to severe depressive symptoms were present in 27% of young, 15% middle-aged and 9% older adults. Younger age, female gender, not partnered, higher anxiety, and poorer health were associated with elevated depressive symptoms. Staying at home/not attending social gatherings were minor contributors to depressive symptoms in young and middle-aged adults. These were not significant in older adults. Social distancing was a marginal contributor in middle-aged and near significant in older adults, but not significant in young adults. CONCLUSIONS: The occurrence of depressive symptoms is decreasing with advancing age. Increased risk of depressive symptoms was associated with being a younger adult, females, single/divorced, poorer health and higher anxiety. In all age groups, the presence of depressive symptoms was greater than global estimates preceding the COVID-19 pandemic. Social restrictions amid the COVID-19 pandemic were marginal risks for depressive symptoms.

Linkage and association analyses of type 2 diabetes/impaired glucose metabolism and adiponectin serum levels in Japanese Americans from Hawaii.

Type 2 diabetes is a common disorder associated with obesity. Lower plasma levels of adiponectin were associated with type 2 diabetes. Candidate regions on chromosomes 1 ( approximately 70 cM) and 14 ( approximately 30 cM) were evaluated for replication of suggestive linkage results for type 2 diabetes/impaired glucose homeostasis in an independent sample of Japanese Americans. Replication of independent linkage evidence for serum levels of adiponectin on chromosome 14 was also evaluated. We investigated 529 subjects from 175 sibships who were originally part of the Honolulu Heart Program. Analyses included nonparametric linkage and association using SAGE (Statistical Analysis for Genetic Epidemiology) and FBAT (family-based test of association) programs and Monte Carlo simulation of Fisher's exact test in SAS. For type 2 diabetes/impaired glucose metabolism, nominal linkage evidence (P < 0.02) followed-up by genotypic association (P = 0.016) was found with marker D14S297 at 31.8 cM; linkage analyses using only diabetes phenotype were also nominally significant at this marker (P < 0.02). Nominal evidence for genotypic association to adiponectin serum level phenotype (P = 0.04) was found with the marker D14S1032 at 23.2 cM. The present study was limited by relatively small sample size. Nevertheless, these results corroborate earlier studies, suggesting that further research is warranted in the candidate region approximately 30 cM on chromosome 14.

Are HIV-Infected Older Adults Aging Differently?

With increasing success in treating HIV, infected persons are living longer, and a new challenge has emerged - the need to understand how HIV-infected adults are aging. What are the similarities with typical aging and what are the unique aspects that may have resulted from HIV infection, interacting with characteristic life style factors and other comorbid conditions? Are specific diseases and conditions (comorbidities), typically seen as part of the aging process, occurring at accelerated rates or with higher frequency (accentuated) in HIV-infected adults? At this juncture, conclusions should be tentative. Certainly, biological processes that correlate with aging occur earlier in the older adult HIV population. Clinical manifestations of these biological processes are age-associated illnesses occurring in greater numbers (multimorbidity), but they are not accelerated. Specifically cardiovascular disease, certain cancers, and renal disease are more common with other comorbidities less certain. Management of this elevated risk for developing multimorbidity is a major concern for patients and their health care teams. The medical system must respond to the evolving needs of this aging and growing older adult population who will dominate the epidemic. Adopting a more holistic approach to their health care management is needed to achieve optimal health and well-being in the HIV-infected older adult. Geriatric care principles best embody this approach.

Predicting death over 8 years in a prospective cohort of HIV-infected women: the Women's Interagency HIV Study.

OBJECTIVES: Predicting mortality in middle-aged HIV-infected (HIV+) women on antiretroviral therapies (ART) is important for understanding the impact of HIV infection. Several health indices have been used to predict mortality in women with HIV infection. We evaluated: (1) an HIV biological index, Veterans Aging Cohort Study (VACS); (2) a physical index, Fried Frailty Index (FFI); and (3) a mental health index, Center for Epidemiologic Studies-Depression (CES-D). Proportional hazards regression analyses were used to predict death and included relevant covariates. DESIGN: Prospective, observational cohort. SETTING: Multicentre, across six sites in the USA. PARTICIPANTS: 1385 multirace/ethnic ART-experienced HIV+ women in 2005. PRIMARY AND SECONDARY OUTCOMES: All deaths, AIDS deaths and non-AIDS deaths up to ~8 years from baseline. RESULTS: Included together in one model, VACS Index was the dominant, significant independent predictor of all deaths within 3 years (HR=2.20, 95% CI 1.83, 2.65, χ2=69.04, p<0.0001), and later than 3 years (HR=1.55, 95% CI 1.30, 1.84, χ2=23.88, p<0.0001); followed by FFI within 3 years (HR=2.06, 95% CI 1.19, 3.57, χ2=6.73, p=0.01) and later than 3 years (HR=2.43, 95% CI 1.58, 3.75, χ2=16.18, p=0.0001). CES-D score was not independently associated with mortality. CONCLUSIONS AND RELEVANCE: This is the first simultaneous evaluation of three common health indices in HIV+ adults. Indices reflecting physical and biological ageing were associated with death.

Elevated aortic pulse wave velocity, a marker of arterial stiffness, predicts cardiovascular events in well-functioning older adults.

BACKGROUND: Aging results in vascular stiffening and an increase in the velocity of the pressure wave as it travels down the aorta. Increased aortic pulse wave velocity (aPWV) has been associated with mortality in clinical but not general populations. The objective of this investigation was to determine whether aPWV is associated with total and cardiovascular (CV) mortality and CV events in a community-dwelling sample of older adults. METHODS AND RESULTS: aPWV was measured at baseline in 2488 participants from the Health, Aging and Body Composition (Health ABC) study. Vital status, cause of death and coronary heart disease (CHD), stroke, and congestive heart failure were determined from medical records. Over 4.6 years, 265 deaths occurred, 111 as a result of cardiovascular causes. There were 341 CHD events, 94 stroke events, and 181 cases of congestive heart failure. Results are presented by quartiles because of a threshold effect between the first and second aPWV quartiles. Higher aPWV was associated with both total mortality (relative risk, 1.5, 1.6, and 1.7 for aPWV quartiles 2, 3, and 4 versus 1; P=0.019) and cardiovascular mortality (relative risk, 2.1, 3.0, and 2.3 for quartiles 2, 3, and 4 versus 1; P=0.004). aPWV quartile was also significantly associated with CHD (P=0.007) and stroke (P=0.001). These associations remained after adjustment for age, gender, race, systolic blood pressure, known CV disease, and other variables related to events. CONCLUSIONS: Among generally healthy, community-dwelling older adults, aPWV, a marker of arterial stiffness, is associated with higher CV mortality, CHD, and stroke.

Walking may be related to less vascular stiffness in the Activity Counseling Trial (ACT).

BACKGROUND: The ACT was a clinical trial of various patient education and counseling interventions to increase physical activity in sedentary primary care populations. It provided the opportunity to measure the effect of increasing physical activity on aortic pulse wave velocity (APWV), a measure of vascular stiffness, in a relatively healthy middle-aged population. The effects of the interventions, as well as the impact of walking and correlates such as older age and maximal oxygen uptake (VO2max), on APWV were assessed. METHODS: The participants in this study were a subset of the 874 persons recruited for the ACT. Information about self-reported physical activity and disease status was collected at baseline (464 persons), 6-month (528 persons), and 24-month (555 persons) intervals. Physiological measures included APWV, systolic blood pressure, and other correlates. RESULTS: In multivariate analyses, the various treatment arms did not have a significant effect on APWV. However, walking in hours per day was associated with slower APWV times or less stiffness (P = .03). This was significant for women and consistent but not significant for men. In addition, age, clinic site, race, systolic blood pressure, and VO2max were independently associated with APWV. CONCLUSIONS: Increased walking frequency over a 24-month period was predictive of reduced vascular stiffness in ACT. The more significant result for walking frequency in women than in men might be caused by the presence of a low Vo2max or physical activity threshold for an effect of walking on APWV, which most women achieved but most men had surpassed at the start of the study. Although needing confirmation because this was a secondary analysis, modest physical activity may have a beneficial effect on large vessel structure.

Head injury in early adulthood and the lifetime risk of depression.

BACKGROUND: Depressive symptoms are common and can be debilitating in the months after head injury. Head injury can also have long-term cognitive effects, but little is known about the long-term risk of depression associated with head injury. We investigated the lifetime rates of depressive illness 50 years after closed head injury. METHODS: Participants were male World War II veterans who served during 1944-1945 and were hospitalized at that time for a head injury, pneumonia, or laceration, puncture, or incision wounds. We used military medical records to establish the presence and severity of closed head injuries. Veterans with (n = 520) and without (n = 1198) head injuries were interviewed in 1996-1997 for their lifetime history of depressive illness. Men with dementia were excluded. RESULTS: Veterans with head injury were more likely to report major depression in subsequent years and were more often currently depressed. Using logistic regression and controlling for age and education, the lifetime prevalence of major depression in the head injured group was 18.5% vs 13.4% in those with no head injury (odds ratio = 1.54, 95% confidence interval = 1.17-2.04). Current major depression was detected in 11.2% of the veterans with head injuries vs 8.5% of those without head injury (odds ratio = 1.63, 95% confidence interval = 1.07-2.50). This increase in depression could not be explained by a history of myocardial infarction, a history of cerebrovascular accident, or history of alcohol abuse. The lifetime risk of depression increased with severity of the head injury. CONCLUSION: The risk of depression remains elevated for decades following head injury and seems to be highest in those who have had a severe head injury.

Variability in midlife systolic blood pressure is related to late-life brain white matter lesions: the Honolulu-Asia Aging study.

BACKGROUND AND PURPOSE: Although white matter lesions (WMLs) on brain MRI in older persons are common, the mechanisms are unclear. Besides the associations with advanced age and high blood pressure (BP), variability in systolic BP (SBP) and the resulting changes in blood flow to the deep arteries of the brain may be contributing factors. METHODS: Japanese-American men in Hawaii have participated in a long-term study of cardiovascular disease, including midlife BP measurements at 3 clinical examinations in the period from 1965 to 1974. In the period from 1991 to 1993, dementia status was added to the fourth examination, and a brain MRI was completed in a fifth examination, which was from 1994 to 1996, on a subset of 575 men, who averaged 82 years. WMLs and ventricular atrophy were determined as the upper fifth in a standardized semiquantitative measure. Excess SBP variability was defined as greater than average increases in BP measurements from up to 3 examinations over 6 years. Logistic regression was used for the association of this variability with WMLs and atrophy, controlling for age, apolipoprotein E4 status, dementia diagnosis, and history of stroke. RESULTS: There were significant (2-fold) increased risks for WMLs among those with moderate and high SBP variability (third and fifth quintiles compared with the lowest quintile). Those in the highest SBP variability category (the fifth quintile) also had significantly more atrophy. CONCLUSIONS: These SBP variability-MRI relationships suggest that variation in SBP in midlife may be a contributing factor to the development of WMLs and ventricular atrophy in late life.

Relation of heart rate at rest and mortality in the Women's Health and Aging Study.

Increased heart rate (HR) has been shown to be associated with increased risk of all-cause and heart disease mortality. However, HR as a health indicator in disabled older women has not been closely examined. The purpose of this study is to assess the association between HR and 3-year mortality in disabled older women. HR at rest was measured using the electrocardiogram. Three groups were categorized by baseline HR (beats per minute): (1) <60, (2) 60 to 89, and (3) >/=90. The survival rate over 3 years was examined. For the total population, age-adjusted 3-year mortality was nearly 40% for the HR >/=90 group, compared with <20% mortality in the HR 60 to 89 group. Women with a HR <60 beats/min had similar mortality to those with HRs 60 to 89 beats/min. Among women with no heart disease and normal electrocardiograms, mortality was slightly lower in all groups, but the association of elevated HR with increased mortality remained. In Cox proportional hazard models, after adjustment for age, number of diseases, medications, blood pressure, smoking status, body mass index, ankle-brachial index, activity status, physical performance score, and forced expiratory volume in the first second, there remained a twofold increase in the risk of death for the HR >/=90 group. Subclinical conditions not measured in this study, such as mild heart failure, may be associated with both increased HR and mortality; this may explain the relation. In patients with and without heart disease, further investigation of cardiovascular status may be warranted if their HR is >/=90 beats/min.

Using the NIH Toolbox in special populations: considerations for assessment of pediatric, geriatric, culturally diverse, non-English-speaking, and disabled individuals.

BACKGROUND: In order to develop health outcomes measures that are relevant and applicable to the general population, it is essential to consider the needs and requirements of special subgroups, such as the young, elderly, disabled, and people of different ethnic and cultural backgrounds, within that population. METHODS: The NIH Toolbox project convened several working groups to address assessment issues for the following subgroups: pediatric, geriatric, cultural, non-English-speaking, and disabled. Each group reviewed all NIH Toolbox instruments in their entirety. RESULTS: Each working group provided recommendations to the scientific study teams regarding instrument content, presentation, and administration. When feasible and appropriate, instruments and administration procedures have been modified in accordance with these recommendations. CONCLUSION: Health outcome measurement can benefit from expert input regarding assessment considerations for special subgroups.

Norming plans for the NIH Toolbox.

OBJECTIVE: The NIH Toolbox for Assessment of Neurological and Behavioral Function (NIH Toolbox) is a comprehensive battery of brief assessment tools. The purpose of this article is to describe plans to establish normative reference values for the NIH Toolbox measures. METHODS: A large sample will be obtained from the US population for the purpose of calculating normative values. The sample will be stratified by age (ages 3-85 years), sex, and language preference (English or Spanish) and have a total sample size of at least 4,205. The sample will include a minimum of 25-100 individuals in each targeted demographic and language subgroup. RESULTS: Norming methods will include poststratification adjustment calculated using iterative proportional fitting, also known as raking, so that the weighted sample will have the same distribution on key demographic variables as the US population described in the 2010 Census. CONCLUSIONS: As with any set of norms, users should be mindful of the reference population and make conclusions consistent with the limitations of normative sampling, since it is not a probability-based sample. However, the NIH Toolbox norming study has been designed to minimize bias and maximize representativeness and precision of estimates. The availability of a "toolbox" of normed measures will be an important foundation for addressing critical research questions in neurologic and behavioral health.

Cognition assessment using the NIH Toolbox.

Cognition is 1 of 4 domains measured by the NIH Toolbox for the Assessment of Neurological and Behavioral Function (NIH-TB), and complements modules testing motor function, sensation, and emotion. On the basis of expert panels, the cognition subdomains identified as most important for health, success in school and work, and independence in daily functioning were Executive Function, Episodic Memory, Language, Processing Speed, Working Memory, and Attention. Seven measures were designed to tap constructs within these subdomains. The instruments were validated in English, in a sample of 476 participants ranging in age from 3 to 85 years, with representation from both sexes, 3 racial/ethnic categories, and 3 levels of education. This report describes the development of the Cognition Battery and presents results on test-retest reliability, age effects on performance, and convergent and discriminant construct validity. The NIH-TB Cognition Battery is intended to serve as a brief, convenient set of measures to supplement other outcome measures in epidemiologic and longitudinal research and clinical trials. With a computerized format and national standardization, this battery will provide a "common currency" among researchers for comparisons across a wide range of studies and populations.

Comorbidities and depression in older adults with HIV.

OBJECTIVE: To investigate whether the high rates of depression found in older adults living with HIV are associated with the number and types of comorbidities. METHODS: The Research on Older Adults with HIV (ROAH) study collected self-reported health data on ~1000 New York City HIV-positive men and women aged 50 years and older. Participants provided data on health problems experienced in the past year and depressive symptomatology (Center for Epidemiological Studies Depression Scale (CES-D)). Data were analysed using a non-parametric test of association and multiple regression analysis. RESULTS: The correlation between CES-D scores and number of comorbidities was significant (r=0.24). In multivariate analyses, depression remained a significant covariate of the number of comorbid conditions, in addition to female gender, inadequate income, history of drug and alcohol use, AIDS diagnosis and self-rated health. Correlations of depression with specific comorbidities varied. Significant correlations with sensory loss and dermatological problems were observed. Significant correlations existed with heart and respiratory conditions as well as fractures, but the directionality of these cross-sectional relationships is uncertain. CONCLUSIONS: The findings suggest the need for further longitudinal research to understand how high rates of depressive symptoms are related to comorbidities. Focussed clinical care that strives to prevent the collapse of the immune system must evolve into an effective treatment strategy for multimorbidities, where HIV is but one of many other chronic illnesses. If the management of depression continues to be a low priority, the older person with HIV may experience an avoidable reduction in life expectancy.

Age and comorbidity impact surgical therapy in older bladder carcinoma patients: a population-based study.

BACKGROUND: Bladder carcinoma often occurs in older patients who also may have other comorbid conditions that could influence the administration of surgical therapy. The current study was conducted to describe the distribution of comorbid conditions in patients with bladder carcinoma and ascertain whether these conditions, as grouped by the American Society of Anesthesiologists physical status classification, affected the choice of surgical therapy. METHODS: The authors examined six population-based cancer registries from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program in 1992. A total of 820 individuals age 55 years and older was found. A random sample of newly diagnosed bladder carcinoma patients were stratified according to registry, age group (ages 55-64 yrs, ages 65-74 yrs, and age 75 yrs and older), and gender. Data regarding comorbid conditions were abstracted from the medical records and merged with routinely collected cancer registry data. The main outcome measures were the prevalence and distribution of comorbid conditions, American Society of Anesthesiologists physical status classification, and the receipt of cystectomy in patients with muscle invasion. RESULTS: Hypertension, chronic pulmonary disease, arthritis, and heart disease were found to affect at least 15% of the study population. Approximately 38% of patients were current or former smokers. Greater than 90% of patients with superficial disease were treated with transurethral resection alone. Among those patients with muscle invasion, only 55% of those ages 55-59 years underwent cystectomy; this percentage dropped to 4% in patients age 85 years and older. Among patients with an American Society of Anesthesiologists physical status classification of 0-2, the cystectomy rate ranged from 53% in those ages 55-59 years to 9% in those age 85 years and older. CONCLUSIONS: There were no significant treatment differences noted with regard to age among patients with superficial disease. Among those patients with muscle invasion, those age 75 years and older were less likely to undergo radical cystectomy (14%) compared with patients ages 55-64 years (48%) and those ages 65-74 years (43%). Patient age may contribute to treatment decisions in patients with muscle-invasive disease, even when comorbidity is taken into account.