This study examined the course of neuropsychological functioning in patients with chronic myelogeous leukemia (n = 91) or myelodysplastic syndrome (n = 15) who underwent standard treatment for their disease or allogeneic hematopoietic stem cell transplantation (HSCT) at baseline, 12 months, and 18 months post-treatment. At baseline, 23% of the participants (n = 75) in the longitudinal sample had Z-scores on at least one of the neuropsychological tests that were <1.4. Participants in the study showed improvement over baseline at the 12 and 18 months assessments. The average Z-scores for the six cognitive domains in the longitudinal data set over the course of the study ranged from −0.89 to 0.59. Significant predictors of change in neuropsychological test scores included age, with older participants showing less improvement over time. Other predictors included baseline cognitive domains (language, memory, and attention), previous cocaine use, disease status, intelligence quotient, and quality of life measures. Findings support previous studies in patients with hematological malignancies who showed cognitive impairments at baseline prior to HSCT. However, there was little evidence for further cognitive decline over the course of 18 months.
Cancer; Neuropsychology; Hematological malignancy; Cognition; Cancer treatment; Hematopoietic stem cell transplantation
Despite the well-documented observation of odor identification deficits in schizophrenia, less is known about where the disruption in the process of correctly identifying an odor occurs. This study aimed to determine the potential moderating effects of semantic processing on the observed olfactory dysfunction in schizophrenia. Schizophrenia patients and healthy comparison subjects completed two versions of the University of Pennsylvania Smell Identification Test (UPSIT): an uncued free-response version and the standard multiple-choice paradigm, as well as three semantic measures: The Boston Naming Test, Animal Naming, and Pyramids and Palm Tree Test. Schizophrenia patients yielded significantly lower scores than the comparison group on the standard UPSIT and on semantic measures. No relationship was observed between olfactory and semantic task performance in patients. These data suggest that odor identification deficits may not be primarily due to semantic processing deficits in schizophrenia.
Schizophrenia; Semantic processing; Olfactory; Olfaction; Smell; Boston naming test
Cognitive difficulties appear to be a more prevalent clinical feature in progressive supranuclear palsy (PSP) than previously thought, and significant cognitive impairment is prevalent in a majority of patients PSP patients not considered clinically demented. The neurocognitive performance of 200 patients with PSP across multiple sites was examined with a variety of commonly used neuropsychological tests. Results indicate primary executive dysfunction (e.g., 74% impaired on the Frontal Assessment Battery, 55% impaired on Initiation/Perseveration subscale of the Dementia Rating Scale), with milder difficulties in memory, construction, and naming. These results have important clinical implications for providers following patients with PSP.
Progressive supranuclear palsy; Frontal-executive; Parkinsonism; Dementia; Memory
Cognitive impairment is common among individuals with heart failure. The purpose of this study was to compare cognitive profiles of individuals with systolic and diastolic dysfunction. Eighty individuals with heart failure completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Mini-Mental State Examination, Trail Making Test, and letter fluency. Approximately 25% of individuals with systolic dysfunction were impaired on the RBANS Total Scale score, compared with only 3% in the diastolic group. Additionally, individuals with systolic dysfunction scored lower than those with diastolic dysfunction on tests of immediate and delayed memory. The groups did not differ on tests of visuospatial skills, but there were mixed results on the RBANS Attention and Language subtests. Overall, the results of this study suggest that individuals with different types of cardiac dysfunction (systolic and diastolic dysfunction) demonstrate differential patterns of performance on neuropsychological tests. These findings have important clinical implications.
Cardiovascular disease; Executive function; Learning and memory; Mild cognitive impairment; Assessment
Limited research is available regarding the impact of neuropsychological functioning on health risk behaviors in rural-dwelling elderly populations. This cross-sectional study examined the relationships between estimated premorbid verbal IQ (AMNART), executive functioning impairment (EXIT25), and health risk behaviors including alcohol use (AUDIT), smoking, compliance with recommended cancer screenings, and obesity (BMI). The total sample included 456 English-speaking adults and older adults of non-Hispanic White and Hispanic origin seen as part of an ongoing study of rural cognitive aging, Project FRONTIER. Regression analyses revealed significant independent effects of AMNART and EXIT25 on most health risk behaviors, and supported the hypothesized mediating role of EXIT25 on the relationships between AMNART and smoking, cancer screenings, and BMI in both cognitively impaired and healthy subgroups. This study clarifies the relationships between executive functioning, premorbid IQ, and health risk behaviors in diverse groups, and confirms that premorbid IQ represents an important determinant of health behaviors and neurocognitive outcomes.
Executive functioning; Diversity; Cognition; Health risk behaviors; Premorbid verbal IQ; geriatrics
Executive dysfunction (ED) is a characteristic of Huntington disease (HD), but its severity and progression is less understood in the prodromal phase, e.g., before gross motor abnormalities. We examined planning and problem-solving abilities using the Towers Task in HD mutation-positive individuals without motor symptoms (n = 781) and controls (n = 212). Participants with greater disease progression (determined using mutation size and current age) performed more slowly and with less accuracy on the Towers Task. Performance accuracy was negatively related to striatal volume while both accuracy and working memory were negatively related to frontal white matter volume. Disease progression at baseline was not associated with longitudinal performance over 4 years. Whereas the baseline findings indicate that ED becomes more prevalent with greater disease progression in prodromal HD and can be quantified using the Towers task, the absence of notable longitudinal findings indicates that the Towers Task exhibits limited sensitivity to cognitive decline in this population.
Huntington's disease; Genetic disorders; Executive functions; Neuroimaging (structural); Norms/normative studies; Practice effects/reliable change; longitudinal change
Visuospatial stimuli are normally perceived from the global structure to local details. A right-brain stroke often disrupts this perceptual organization, resulting in piecemeal encoding and thus poor visuospatial memory. Using a randomized controlled design, the present study examined whether promoting the global-to-local encoding improves retrieval accuracy in right-brain-damaged stroke survivors with visuospatial memory deficits. Eleven participants received a single session of the Global Processing Training (global-to-local encoding) or the Rote Repetition Training (no encoding strategy) to learn the Rey–Osterrieth Complex Figure. The result demonstrated that the Global Processing Training significantly improved visuospatial memory deficits after a right-brain stroke. On the other hand, rote practice without a step-by-step guidance limited the degree of memory improvement. The treatment effect was observed both immediately after the training procedure and 24 h post-training. Overall, the present findings are consistent with the long-standing principle in cognitive rehabilitation that an effective treatment is based on specific training aimed at improving specific neurocognitive deficits. Importantly, visuospatial memory deficits after a right-brain stroke may improve with treatments that promote global processing at encoding.
Stroke rehabilitation; Visuospatial disorder; Cognitive rehabilitation; Memory rehabilitation; Complex figure; Learning and memory
Increased understanding of the underlying mechanisms of cognitive remediation is needed to facilitate development of intervention strategies for childhood cancer survivors experiencing cognitive late effects. Accordingly, a pilot functional magnetic resonance imaging (fMRI) study was conducted with 14 cancer survivors (12.02 ± 0.09 years old), who participated in a cognitive remediation clinical trial, and 28 healthy children (12.7 ± 0.6 years old). The ventral visual areas, cerebellum, supplementary motor area, and left inferior frontal cortex were significantly activated in the healthy participants during a continuous performance task. In survivors, brain activation in these regions was diminished at baseline, and increased upon completion of remediation and at a 6-month follow-up. The fMRI activation index for each region of interest was inversely associated with the Conners' Clinical Competence Index (p<.01). The pilot study suggests that fMRI is useful in evaluating neural responses to cognitive remediation.
Attention; Brain tumor; Childhood brain insult; Neuroimaging (functional); Rehabilitation
Apathy is a relatively common clinical feature of HIV-Associated Neurocognitive Disorders, but little is known about its implications for everyday functioning outcomes. In the present study, we examined the associations between apathy and self-reported instrumental activities of daily living (IADL) and neurocognitive complaints in 75 participants with HIV infection and 52 demographically comparable seronegative comparison subjects. All volunteers completed the apathy subscale of the Frontal Systems Behavioral Scale as part of a comprehensive neuromedical, psychiatric, and neurocognitive research evaluation. When compared with the seronegative comparison participants, the HIV+ group reported significantly higher current levels of apathy, but did not differ in self-report of prior (i.e., pre-seroconversion) apathy. Higher current apathy self-ratings were associated with greater severity of IADL declines and more numerous cognitive complaints in the HIV+ sample, even after adjusting for potential psychiatric (e.g., depression), medical (e.g., hepatitis C co-infection), and neurocognitive predictors. Cognitive complaints, but not IADLs, were also uniquely associated with ratings of executive dysfunction and disinhibition. All told, these findings suggest that apathy may make a unique contribution to important everyday functioning outcomes among persons living with HIV infection. The clinical detection of apathy may help identify HIV-infected individuals at particular risk for functional impairments who may require additional support to maintain independence.
HIV/AIDS; Activities of daily living; Apathy; Everyday functioning
Although HIV-associated neurocognitive disorders (HAND) are the strong predictors of everyday functioning difficulties, approximately half of all functionally impaired individuals are labeled “neurocognitively normal” according to the standard neuropsychological measures, suggesting that novel predictors of functional problems in this prevalent subgroup are needed. The present study hypothesized that increased neurocognitive intra-individual variability as indexed by dispersion would be associated with poor daily functioning among 82 persons with HIV infection who did not meet research criteria for HAND. An intra-individual standard deviation was calculated across the demographically adjusted T-scores of 13 standard neuropsychological tests to represent dispersion, and functional outcomes included self-reported declines in basic and instrumental activities of daily functioning (basic activity of daily living [BADL] and instrumental activity of daily living [IADL], respectively) and medication management. Dispersion was a significant predictor of medication adherence and dependence in both BADL and IADL, even when other known predictors of functional status (i.e., age, affective distress, and indices of disease severity) were included in the models. As a significant and unique predictor of a performance on the range of daily functioning activities, neurocognitive dispersion may be indicative of deficient cognitive control expressed as inefficient regulation of neurocognitive resources in the context of competing functional demands. As such, dispersion may have clinical utility in detecting risk for functional problems among HIV-infected individuals without HAND.
HIV; Everyday functioning; Neuropsychological assessment; Variability; AIDS dementia complex; Treatment compliance
This joint position paper of the American Academy of Clinical Neuropsychology and the National Academy of Neuropsychology sets forth our position on appropriate standards and conventions for computerized neuropsychological assessment devices (CNADs). In this paper, we first define CNADs and distinguish them from examiner-administered neuropsychological instruments. We then set forth position statements on eight key issues relevant to the development and use of CNADs in the healthcare setting. These statements address (a) device marketing and performance claims made by developers of CNADs; (b) issues involved in appropriate end-users for administration and interpretation of CNADs; (c) technical (hardware/software/firmware) issues; (d) privacy, data security, identity verification, and testing environment; (e) psychometric development issues, especially reliability, and validity; (f) cultural, experiential, and disability factors affecting examinee interaction with CNADs; (g) use of computerized testing and reporting services; and (h) the need for checks on response validity and effort in the CNAD environment. This paper is intended to provide guidance for test developers and users of CNADs that will promote accurate and appropriate use of computerized tests in a way that maximizes clinical utility and minimizes risks of misuse. The positions taken in this paper are put forth with an eye toward balancing the need to make validated CNADs accessible to otherwise underserved patients with the need to ensure that such tests are developed and utilized competently, appropriately, and with due concern for patient welfare and quality of care.
Computerized testing; Neurocognition; Neuropsychological test validity
Repeated assessments are a relatively common occurrence in clinical neuropsychology. The current paper will review some of the relevant concepts (e.g., reliability, practice effects, alternate forms) and methods (e.g., reliable change index, standardized based regression) that are used in repeated neuropsychological evaluations. The focus will be on the understanding and application of these concepts and methods in the evaluation of the individual patient through examples. Finally, some future directions for assessing change will be described.
Reliable change; Practice effects; Assessment
The serial position effect shows that two interrelated cognitive processes underlie immediate recall of a supraspan word list. The current study used item response theory (IRT) methods to determine whether the serial position effect poses a threat to the construct validity of immediate list recall as a measure of verbal episodic memory. Archival data were obtained from a national sample of 4,212 volunteers aged 28–84 in the Midlife Development in the United States study. Telephone assessment yielded item-level data for a single immediate recall trial of the Rey Auditory Verbal Learning Test (RAVLT). Two parameter logistic IRT procedures were used to estimate item parameters and the Q1 statistic was used to evaluate item fit. A two-dimensional model better fit the data than a unidimensional model, supporting the notion that list recall is influenced by two underlying cognitive processes. IRT analyses revealed that 4 of the 15 RAVLT items (1, 12, 14, and 15) were misfit (p < .05). Item characteristic curves for items 14 and 15 decreased monotonically, implying an inverse relationship between the ability level and the probability of recall. Elimination of the four misfit items provided better fit to the data and met necessary IRT assumptions. Performance on a supraspan list learning test is influenced by multiple cognitive abilities; failure to account for the serial position of words decreases the construct validity of the test as a measure of episodic memory and may provide misleading results. IRT methods can ameliorate these problems and improve construct validity.
Learning and memory; Assessment; Statistical methods
Late-life minor depression (miD) is a prevalent but poorly understood illness. Verbal learning and memory profiles have commonly been used to characterize neuropsychiatric disorders. This study compared the performance of 27 older adults with miD on the California Verbal Learning Test (CVLT) with 26 age-matched individuals with Major Depressive Disorder (MDD) and 36 non-depressed controls. Results revealed that the miD group performed comparably with controls and significantly better than the MDD group on several CVLT indices. Moreover, cluster analysis revealed three distinct groups, consistent with theoretical representations of “normal,” “subcortical,” and “cortical” verbal learning and memory profiles. The majority of the miD group showed “normal” profiles (74%), whereas most individuals with MDD displayed “subcortical” profiles (54%). The findings suggest that depression in the elderly is a heterogeneous entity and that the CVLT may be a useful tool for characterizing learning and memory in late-onset depressive disorders.
Depression; Minor; Elderly; Late-onset; CVLT; Verbal learning and memory
The Effort Index (EI) of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was developed to identify inadequate effort. Although researchers have examined its validity, the reliability of the EI has not been evaluated. The current study examined the temporal stability of the EI across 1 year in two independent samples of older adults. One sample consisted of 445 cognitively intact older adults (mean age = 72.89; 59% having 12–15 years of education) and the second sample consisted of 51 individuals diagnosed with amnestic Mild Cognitive Impairment (mean age = 82.41; 41% having 12–15 years of education). For both samples, the EI was found to have low stability (Spearman's ρ = .32–.36). When participants were divided into those whose EI stayed stable or improved versus those whose EI worsened (i.e., declining effort) on retesting, it was observed that individuals with lower baseline RBANS Total scores tended to worsen on the EI across time. Overall, the findings suggest low temporal stability of the EI in two geriatric samples. In particular, individuals with poorer cognition at baseline could present with poorer effort across time. These findings also suggest the need to further examine the temporal stability of other effort measures.
Malingering/symptom validity testing; Elderly/geriatrics/aging; Mild cognitive impairment
Individuals with substance use disorders (SUDs) commonly report lapses in prospective memory (PM) in their daily lives; however, our understanding of the profile and predictors of laboratory-based PM deficits in SUDs and their associations with everyday PM failures is still very preliminary. The current study examined these important questions using well-validated measures of self-report and laboratory-based PM in a mixed cohort of 53 SUD individuals at treatment entry and 44 healthy adults. Consistent with prior research, the SUD group endorsed significantly more self-cued and environmentally based PM failures in their daily lives. Moreover, the SUD group demonstrated significantly lower time-based PM performance, driven largely by cue detection errors. The effect of SUDs on PM was particularly strong among participants with fewer years of education. Within the SUD cohort, time-based PM was correlated with clinical measures assessing executive functions, retrospective memory, and psychomotor speed. Importantly, time-based PM was uniquely associated with elevated PM failures in daily lives of the SUD participants, independent of current affective distress and other neurocognitive deficits. Findings suggest that individuals with SUD are vulnerable to deficits in PM, which may in turn increase their risk for poorer everyday functioning outcomes (e.g., treatment non-compliance).
Episodic memory; Polydrug abuse; Drug rehabilitation; Activities of daily living; Neuropsychological assessment
The Iowa Gambling Task (IGT) is assumed to measure executive functioning, but this has not been empirically tested by means of both convergent and discriminant validity. We used structural equation modeling (SEM) to test whether the IGT is an executive function (EF) task (convergent validity) and whether it is not related to other neuropsychological domains (discriminant validity). Healthy community-dwelling participants (N = 214) completed a comprehensive neuropsychological battery. We analyzed the conventional IGT metric and three alternative metrics based on the overall difference of advantageous minus disadvantageous choices made during the last 60 IGT responses and advantageous minus disadvantageous choices based on two specific decks of cards (D minus A). An a priori six-factor hierarchical model of neuropsychological functioning was confirmed with SEM. Attention and processing speed were grouped as “non-associative” factors. Fluency, executive functioning, visual learning/memory, and verbal learning/memory were grouped as higher-level “associative” factors. Of the non-associative factors, attention, but not speed, predicted IGT performance. When each associative factor was entered along with attention, only EF improved the model fit and that was only for metrics based on trials 41–100. SEM indicates metrics based on trails 1–100 are influenced by attention, and metrics based on trails 41–100 are influenced by attention and EF. Its associative strength with attention is twice that of EF. Conceptually, the IGT is a multi-trait task involving novel problem-solving and attentional domains to a greater extent, and executive functioning to a lesser extent.
Iowa Gambling Task; Decision-making; Executive function; Neuropsychological evaluation; Structural equation modeling
Formulae to estimate premorbid memory functioning in a sample of cognitively intact older adults have been developed. These formulae were validated in a small sample of patients with amnestic Mild Cognitive Impairment. However, further validation is clearly needed. The current study applied these formulae to a sample of 1,059 patients referred to a dementia clinic and compared the premorbid estimates of memory functioning with current memory abilities. Large and statistically significant differences were observed in the current sample, with premorbid memory scores exceeding current memory scores. Although some cautions should be observed when using these estimates clinically, growing support for these estimates of premorbid memory abilities may aid clinicians in determining change across time in older patients.
Predicting cognition; Learning and memory; Assessment
Use of normative data stratified by education may result in misclassification of African American older adults because reading ability, an estimate of educational attainment, is lower than reported years of education for some African American elders. This study examined the contribution of reading ability versus education to neuropsychological test performance in 86 community-dwelling African American elders ages 56–91 with 8–18 years of education. Hierarchical multiple regression analyses revealed that reading ability, but not education, was significantly associated with performances on the Trail Making Test, Controlled Oral Word Association Test, Animal Naming, Digit Span, and the Stroop test. Reading ability was not significantly related to performances on measures of memory. Medium to large effect sizes (Cohen's d = 0.58–1.41) were found when comparing mean performances on neuropsychological measures in groups with low versus high reading scores. Results indicate that reading ability contributes beyond educational attainment to performances on some neuropsychological measures among African American elders. These findings have implications for reducing misclassification among minority populations through the use of appropriate normative data.
Assessment; Elderly; Geriatrics; Aging; Norms; Normative studies
This study examined the association between recent trends in CD4 and viral loads and cognitive test performance with the expectation that recent history could predict cognitive performance. Eighty-three human immunodeficiency virus (HIV)-infected patients with a mean CD4 count of 428 copies/ml were examined in this study (62% with undetectable plasma viral load [PVL]). We investigated the relationships between nadir CD4 cell count, 1-year trends in immunologic function/PVLs, and cognitive performance across several domains using linear regression models. Nadir CD4 cell count was predictive of current executive function (p = .004). One year clinical history for CD4 cell counts and/or PVLs were predictive of executive function, attention/working memory, and learning/memory measures (p < .05). Models that combined recent clinical history trends and nadir CD4 cell counts suggested that recent clinical trends were more important in predicting current cognitive performance for all domains except executive function. This research suggests that recent CD4 and viral load history is an important predictor of current cognitive function across several cognitive domains. If validated, clinical variables and cognitive dysfunction models may improve our understanding of the dynamic relationships between disease evolution and progression and CNS involvement.
HIV; Cognition; Neuropsychology; Executive function; Recent clinical history
The Montreal Cognitive Assessment (MoCA) screen was developed as a brief instrument to identify mild cognitive impairment and dementia among older individuals. To date, limited information is available regarding the neuroimaging signatures associated with performance on the scale, or the relationship between the MoCA and more comprehensive cognitive screening measures. The present study examined performances on the MoCA among 111 non-clinical older adults (ages 51–85) enrolled in a prospective study of cognitive aging. Participants were administered the MoCA, Mini-Mental State Exam (MMSE), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A subset of participants (N = 69) underwent structural 3 T magnetic resonance imaging (MRI) to define the volumes of total frontal gray matter, total hippocampus, T2-weighted subcortical hyperintensities (SH), and total brain volume. The results revealed significant correlations between the total score on the MoCA and total score on the RBANS and MMSE, though the strength of the correlations was more robust between the MoCA and the RBANS. Modest correlations between individual subscales of the MoCA and neuroimaging variables were evident, but no patterns of shared variance emerged between the MoCA total score and neuroimaging indices. In contrast, total brain volume correlated significantly with total score on the RBANS. These results suggest that additional studies are needed to define the significance of MoCA scores relative to brain integrity among an older population.
Mild cognitive impairment; Neuroimaging (structural)
The Boston Naming Test is one of the most widely used neuropsychological instruments; yet, there has been limited use of modern psychometric methods to investigate its properties at the item level. The current study used Item response theory to examine each item's difficulty and discrimination properties, as well as the test's measurement precision across the range of naming ability. Participants included 300 consecutive referrals to the outpatient neuropsychology service at Mayo Clinic in Florida. Results showed that successive items do not necessarily reflect a monotonic increase in psychometric difficulty, some items are inadequate to distinguish individuals at various levels of naming ability, multiple items provide redundant psychometric information, and measurement precision is greatest for persons within a low-average range of ability. These findings may be used to develop short forms, improve reliability in future test versions by replacing psychometrically poor items, and analyze profiles of intra-individual variability.
Boston Naming Test; Item response theory; Item difficulty; Item discriminability
Questions have been raised about whether poor performance on memory tasks by individuals with major depressive disorder (MDD) might be the result of poor or variable effort or disease-related disruption of neural circuits supporting memory functions. The present study examined performance on a measure of task engagement and on an auditory memory task among 45 patients with MDD (M age = 47.82, SD = 19.55) relative to 32 healthy controls (HC; M age = 51.03, SD = 22.09). One-hundred percent of HC and MDD volunteers performed above the threshold for adequate effort on a formal measure of task engagement. The MDD subjects performed significantly more poorly than the HC subjects on an auditory learning and memory test. The present results suggest that auditory memory difficulties do occur among those with MDD and that decrements in performance in this group may be related to factors other than lack of effort.
Depression; Malingering/symptom validity testing; Learning and memory
According to the multi-process theory of prospective memory (ProM), time-based tasks rely more heavily on strategic processes dependent on prefrontal systems than do event-based tasks. Given the prominent frontostriatal pathophysiology of HIV infection, one would expect HIV-infected individuals to demonstrate greater deficits in time-based versus event-based ProM. However, the two prior studies examining this question have produced variable results. We evaluated this hypothesis in 143 individuals with HIV infection and 43 demographically similar seronegative adults (HIV−) who completed the research version of the Memory for Intentions Screening Test, which yields parallel subscales of time- and event-based ProM. Results showed main effects of HIV serostatus and cue type, but no interaction between serostatus and cue. Planned pair-wise comparisons showed a significant effect of HIV on time-based ProM and a trend-level effect on event-based ProM that was driven primarily by the subset of participants with HIV-associated neurocognitive disorders. Nevertheless, time-based ProM was more strongly correlated with measures of executive functions, attention/working memory, and verbal fluency in HIV-infected persons. Although HIV-associated deficits in time- and event-based ProM appear to be of comparable severity, the cognitive architecture of time-based ProM may be more strongly influenced by strategic monitoring and retrieval processes.
AIDS dementia complex; Episodic memory; Executive functions; Neuropsychological assessment