Recently, three accounts have emerged on the role of the anterior temporal lobes (ATLs) in semantic memory. One account claims that the ATLs are domain-general semantic hubs, another claims that they underlie knowledge of unique entities specifically, and yet another account claims that they support social conceptual knowledge generally. Here, we review neuropsychological and neuroimaging studies that bear on these three accounts and offer suggestions for future research to elucidate the roles of the ATLs in semantic memory. (JINS, 2009, 15, 645–649.)

Individual differences associated with age and various neurological conditions are often found in many different neuropsychological and cognitive variables. These variables are frequently treated as though they were independent of one another, with the results interpreted in terms of effects on task-specific processes. However, an alternative perspective evaluates the breadth of the individual difference influences, and takes relations with other variables into account when considering effects on specific neurocognitive variables. This analytical procedure is illustrated in analyses of the WAIS-IV and WMS-IV standardization data, and of data from the Virginia Cognitive Aging Project. (JINS, 2009, 15, 650–661.)

The current study examined temporal order memory in preclinical Huntington’s disease (pre-HD). Participants were separated into less than 5 years (pre-HD near) and more than 5 years (pre-HD far) from estimated age of clinical diagnosis. Participants completed a temporal order memory task on a computerized radial eight-arm maze. On the study phase of each trial, participants viewed a random sequence of circles appearing one at a time at the end of each arm. On the choice phase, participants viewed two circles at the end of the study phase arms and chose the circle occurring earliest in the sequence. The task involved manipulations of the temporal lag, defined as the number of arms occurring in the sample phase sequence between the two choice phase arms. Research suggests that there is more interference for temporally proximal stimuli relative to temporally distal stimuli. There were no significant differences between the pre-HD far group and controls on the temporal order memory task. The pre-HD near group demonstrated significant impairments relative to the other groups on closer temporal lags, but were normal on the furthest temporal lag. Therefore, temporal order memory declines with increased temporal interference in pre-HD close to estimated diagnosis of HD. (JINS, 2009, 15, 662–670.)

Synaptic development and elimination are normal neurodevelopmental processes, which if altered could contribute to various neuropsychiatric disorders. 31P-1H magnetic resonance spectroscopic imaging (MRSI) and structural magnetic resonance imaging (MRI) exams were conducted on 105 healthy children ages 6–18 years old to identify neuromolecular indices of synaptic development and elimination. Over the age range studied, age-related changes in high-energy phosphate (phosphocreatine), membrane phospholipid metabolism (precursors and breakdown products), and percent gray matter volume were found. These neuromolecular and structural indices of synaptic development and elimination are associated with development of several cognitive domains. Monitoring of these molecular markers is essential for devising treatment strategies for neurodevelopmental disorders. (JINS, 2009, 15, 671–683.)

Patients with end-stage renal disease (ESRD) who receive dialysis have been shown to have impaired neuropsychological performance. It remains unclear, however, whether cognitive deficits associated with ESRD and/or dialysis are reversible after successful kidney transplantation. Thus, the main purpose of this study was to longitudinally compare the cognitive performance of adequately dialyzed patients with ESRD before and shortly after kidney transplantation. Twenty-two dialyzed patients with ESRD who subsequently received a kidney transplant, 20 dialyzed patients who were medically qualified and awaiting kidney transplant but did not receive it, and 30 matched controls were the participants for this study. Overall, our results demonstrate that a successful kidney transplant is associated with improved neuropsychological performance in patients with ESRD. Specifically, a significant improvement was seen on measures of psychomotor speed, visual planning, retrieval of learnt material, and abstract thinking. Additionally, the degree of cognitive improvement following kidney transplant was significantly associated with some pre-, intra-, and postoperative factors (e.g., age, duration of chronic kidney disease, postoperative graft function). The results of this study also show that the cognitive performance of adequately dialyzed patients without a kidney transplant, although often below that of matched controls, remains relatively stable over time . (JINS, 2009, 15, 684–694.)

Impairments in executive functioning frequently occur after acquired brain damage, in psychiatric disorders, and in relation to aging. The Brixton Spatial Anticipation Test is a relatively new measure for assessing the ability to detect and follow a rule, an important aspect of executive functioning. To date, normative data on this task are limited, particularly concerning the elderly. This study presents age- and education-adjusted regression-based norms obtained in a group of healthy older participants (n = 283; mean age 67.4 ± 8.5 years). The applicability and validity of these norms were further examined in different groups of patients with stroke (n = 106), diabetes mellitus (n = 376), MCI/early dementia (n = 70), psychiatric disorders (n = 63), and Korsakoff’s syndrome (n = 41). The results showed that patients with Korsakoff’s syndrome, stroke, and psychiatric disorders performed significantly worse than healthy controls. Test-retest correlation (n = 83), learning effects, and correlations with other neuropsychological tests were also explored. Based on the present study, the Brixton test appears a useful addition to existing measures of executive functioning. Moreover, the test can be reliably applied in different groups of clinical patients. (JINS, 2009, 15, 695–703.)

Errorless learning is an intervention that benefits memory performance in healthy older adults and a variety of clinical populations. A limitation of the errorless learning technique is that it is passive and does not involve elaborative processing. We report two studies investigating the added benefits of elaborative, self-generated learning to the errorless learning advantage. We also explored the mnemonic mechanisms of the errorless learning advantage. In both studies, older adults and individuals with amnestic mild cognitive impairment (aMCI) completed four encoding conditions representing the crossing of errorless/errorful learning and self-generated/experimenter-provided learning. Self-generation enhanced the errorless learning benefit in cued recall and cued recognition, but not in free recall or item recognition. An errorless learning advantage was observed for priming of target words, and this effect was amplified for participants with aMCI after self-generated learning. Moreover, the aMCI group showed significant priming of prior self-generated errors. These results demonstrate that self-generation enhances the errorless learning advantage when study and test conditions match. The data also support the argument that errorless learning eliminates the misleading implicit influence of prior errors, as well as the need for explicit memory processes to distinguish targets from errors. (JINS, 2009, 15, 704–716.)

Many U.S. Gulf War-era veterans complained of poor cognition following the war. This study assessed neuropsychological functioning in veterans 10 years after the war through objective tests. 2189 Gulf War-era veterans (1061 deployed, 1128 non-deployed) were examined at 1 of 16 U.S. Veterans Affairs medical centers. Outcomes included neuropsychological domains derived from factor analysis and individual test scores. Deployed veterans performed significantly worse than non-deployed veterans on 2 of 8 factors (motor speed & sustained attention, analysis not corrected for multiple comparisons) and on 4 of 27 individual test variables (Trails A & B, California Verbal Learning Test – List B, and Continuous Performance Test sensitivity, with only Trails B surviving Bonferroni correction). Within deployed veterans, Khamisiyah exposure was negatively correlated with motor speed after controlling for emotional distress. Depressive symptoms and self-reported exposure to toxicants were independently and significantly associated with worse sustained attention. Other factors were also associated with self-reported exposures. The findings were not a result of differential effort across groups. Gulf War deployment is associated with subtle declines of motor speed and sustained attention, despite overall intact neuropsychological functioning. Evidence suggests that toxicant exposures influence both these functions, and depressive symptoms also influence attention. (JINS, 2009, 15, 717–729.)

Research regarding learning in Alzheimer’s disease (AD) patients has been mixed. Learning capacity might be better indexed using a score that reflects the interaction between the learning slope and total recall, referred to as the Cumulative Word Learning (CWL) score. We compared a group of AD patients to normal participants using a traditional index of learning and the CWL score that were derived from the Hopkins Verbal Learning Test – Revised (HVLT-R). The HVLT-R is a supra-span, list-learning test containing 12 words from three semantic categories. The results indicated that the sample of AD patients performed within the average range, using the traditional learning z score. Although mild AD patients were not found to differ from controls in the traditional learning z score, a significant difference was noted for the CWL score. The moderate AD patients differed from the normal controls in both learning measures. Furthermore, unlike the traditional learning score, the CWL score was a significant predictor of overall cognitive functioning, as indexed using their Mini-Mental State Examination (MMSE) score. Thus, the CWL score might be a more sensitive indicator overall of total learning capacity and may be useful in staging Alzheimer’s disease because of increased resilience to floor effects. (JINS, 2009, 15, 730–739.)

Outcome studies on traumatic brain injury (TBI) have shown that functional status can be predicted by demographic, injury severity, and trauma-related factors. Concurrent cognitive functions as one of the determinants of functional outcome is less documented. This study evaluated the effects of concurrent neuropsychological measures on functional outcome 1 year after injury. Neuropsychological data, employment status, self-reported fatigue, and the Glasgow Outcome Scale-Extended (GOSE) were collected from 115 persons with TBI (ranging from mild to severe) at 3 and 12 months postinjury. Principal components analysis was conducted with the neuropsychological measures and three components emerged. Multiple regression analysis, controlling for demographic and injury severity related factors, was used to test the effects of cognitive components at 12 months on functional outcome (GOSE). One year after injury, 64% were categorized as “good recovery” and 36% as “moderate disability” according to GOSE. Good functional recovery depended on shorter duration of posttraumatic amnesia, less fatigue, absence of intracranial pathology, higher education, and better performance on cognitive measures. The predictive values of Verbal/Reasoning and Visual/Perception components are supported; each added significantly and improved prediction of functional outcome. The Memory/Speed component showed a near-significant relationship to outcome. (JINS, 2009, 15, 740–750)

Although memory deficits are typically the earliest and most profound symptoms of Alzheimer’s disease (AD) and mild cognitive impairment (MCI), there is increasing recognition of subtle executive dysfunctions in these patients. The purpose of the present study was to determine the sensitivity of the Behavioral Assessment of the Dysexecutive Syndrome (BADS), and to detect early specific signs of the dysexecutive syndrome in the transition from normal cognition to dementia. The BADS was administered to 50 MCI subjects, 50 mild AD patients, and 50 normal controls. Statistically significant differences were found among the three groups with the AD patients performing most poorly, and the MCI subjects performing between controls and AD patients. The Rule Shift Cards and the Action Program subtests were the most highly discriminative between MCI and controls; the Zoo Map and Modified Six Elements between MCI and AD; and the Action Program, Zoo Map, and Modified Six Elements between AD and controls. These results demonstrate that the BADS is clinically useful in discriminating between normal cognition and progressive neurodegenerative conditions. Furthermore, these data confirm the presence of a dysexecutive syndrome even in mildly impaired elderly subjects. (JINS, 2009, 15, 751–757.)

Scores on the Boston Naming Test (BNT) are frequently lower for African American when compared with Caucasian adults. Although demographically based norms can mitigate the impact of this discrepancy on the likelihood of erroneous diagnostic impressions, a growing consensus suggests that group norms do not sufficiently address or advance our understanding of the underlying psychometric and sociocultural factors that lead to between-group score discrepancies. Using item response theory and methods to detect differential item functioning (DIF), the current investigation moves beyond comparisons of the summed total score to examine whether the conditional probability of responding correctly to individual BNT items differs between African American and Caucasian adults. Participants included 670 adults age 52 and older who took part in Mayo’s Older Americans and Older African Americans Normative Studies. Under a two-parameter logistic item response theory framework and after correction for the false discovery rate, 12 items where shown to demonstrate DIF. Of these 12 items, 6 (“dominoes,” “escalator,” “muzzle,” “latch,” “tripod,” and “palette”) were also identified in additional analyses using hierarchical logistic regression models and represent the strongest evidence for race/ethnicity-based DIF. These findings afford a finer characterization of the psychometric properties of the BNT and expand our understanding of between-group performance. (JINS, 2009, 15, 758–768.)

Clinicians are accustomed to interpreting diagnostic test scores in terms of sensitivity and specificity. Many clinicians also appreciate that sensitivity and specificity need to be interpreted in terms of local base rates (i.e., pretest probability). However, most neuropsychological tests contain a wide range of scores. Important diagnostic information may be sacrificed when valid test scores are reduced to the simple dichotomy of “positive” or “negative” diagnosis that underlies sensitivity and specificity analysis. The purpose of this study is to provide an introduction to multiple-level likelihood ratios, a method for preserving the information in a wider range of scores. These statistics are first described using a hypothetical example of dementia screening, then with patient data from an epilepsy surgery sample. Multiple-level likelihood ratios have several advantages over sensitivity and specificity analysis because they are applied across a wider range of diagnostic scores, and generalize to settings with different base rates. We suggest that the diagnostic validity of many psychological tests may be underestimated by relying solely on traditional dichotomous sensitivity and specificity analysis. (JINS, 2009, 15, 769–776.)

Although several brief sensitive screening tools are available to detect cognitive dysfunction, few have been developed to quickly assess executive functioning (EF) per se. We designed a new brief tool to evaluate EF in neurodegenerative diseases. Patients with an established diagnosis of behavioral variant frontotemporal dementia (bvFTD; n = 22), Alzheimer disease (AD; n = 25), and controls (n = 26) were assessed with a cognitive screening test, the INECO Frontal Screening (IFS), and EF tests. Clinical Dementia Rating Scale (CDR) scores were obtained for all patients. Internal consistency of the IFS was very good (Cronbach’s alpha = .80). IFS total (out of 30 points) was 27.4 (SD = 1.6) for controls, 15.6 (SD = 4.2) for bvFTD, and 20.1 (SD = 4.7) for AD. Using a cutoff of 25 points, sensitivity of the IFS was 96.2%, and specificity 91.5% in differentiating controls from patients with dementia. The IFS correlated significantly with the CDR and executive tasks. The IFS total discriminated controls from demented patients, and bvFTD from AD. IFS is a brief, sensitive, and specific tool for the detection of executive dysfunction associated with neurodegenerative diseases. The IFS may be helpful in the differential diagnosis of FTD and AD. (JINS, 2009, 15, 777–786.)

The frequency and characteristics of closing-in behavior (CIB) were examined in 797 patients with Alzheimer’s disease (AD), 132 of whom were followed up longitudinally. The frequency of CIB increased with the complexity of the graphic copying task and with the severity of Alzheimer’s disease. Regression analyses suggested that attentional deficits are critical factors for the appearance of CIB, but that visuospatial impairments also play an important role in the emergence of severe forms of CIB. (JINS, 2009, 15, 787–792.)

Few studies have evaluated the prevalence of impairments of financial capacity among individuals with psychiatric disorders. Late life depression (LLD) is a common psychiatric disorder associated with significant disability and cognitive impairment. The purpose of this investigation was to determine the prevalence and cognitive correlates of impairments of financial capacity among individuals with LLD. Participants included 65 LLD individuals and 32 comparison subjects. Assessments included measures of financial capacity, cognitive functioning, and depression symptom severity. Individuals with LLD exhibited a significantly higher rate of impaired financial capacity (22%) than the comparison group (6%). Results of a multiple regression analysis indicated that performance on measures of executive functioning and attention, but not depression severity, were most strongly associated with financial capacity performance in LLD. Our results suggest impairments of financial capacity in LLD are largely explained by cognitive functioning in these domains. (JINS, 2009, 15, 793–798.)

We examined differences in response latencies obtained during a validated video-based hazard perception driving test between three healthy, community-dwelling groups: 22 mid-aged (35–55 years), 34 young–old (65–74 years), and 23 old-old (75–84 years) current drivers, matched for gender, education level, and vocabulary. We found no significant difference in performance between mid-aged and young-old groups, but the old-old group was significantly slower than the other two groups. The differences between the old-old group and the other groups combined were independently mediated by useful field of view (UFOV), contrast sensitivity, and simple reaction time measures. Given that hazard perception latency has been linked with increased crash risk, these results are consistent with the idea that increased crash risk in older adults could be a function of poorer hazard perception, though this decline does not appear to manifest until age 75+ in healthy drivers. (JINS, 2009, 15, 799–802.)

Pituitary adenomas, even after successful treatment, are associated with cognitive dysfunctions. We hypothesized that an association between the age of the patients at pituitary surgery and neuropsychological outcome may exist. Forty-two patients (mean age 51 ± 10 years) who had been successfully treated for pituitary adenoma (surgery with or without subsequent radiotherapy) underwent neuropsychological testing. Age at treatment (mean 37 ± 11 years) was significantly associated with Trail Making Test, Part B (TMT-B) results, a measure of executive control and attention (r = .60, p < .0001). This association remained significant after adjustment for age at testing and time since treatment (r = .42, p = .008). No associations were detected between age at treatment and Trail Making Test, Part A (TMT-A, attentional speed), the digit span test (acoustic working memory), and the German version of the Auditory Verbal Learning and Memory, and Memory Test (verbal memory, all p ≥ .3). Our data suggest a favorable effect of younger age at treatment in adults on neurocognitive outcome after surgery for pituitary adenoma. (JINS, 2009, 15, 803–806.)

Neuropsychological data on an extended series of cases of variant Creutzfeldt-Jakob Disease (vCJD) are presented, complementing earlier findings from smaller sample studies of this condition. Distinct neuropsychological features in this extended series included relatively preserved verbal knowledge, immediate verbal memory span, and elementary visual processing. This sparing contrasted with ubiquitous impairment in every vCJD patient on timed tests of verbal fluency and digit-symbol substitution. There were also high rates of impairment on tests of memory, and of visuoperceptual and visuospatial reasoning. Our findings lend support to the view that distinctive neuropsychological features may be one of the diagnostic markers of the condition. (JINS, 2009, 15, 807–810.)