Objectives: Research has shown that analyzing intrusion errors generated on verbal learning and memory measures is helpful for distinguishing between the memory disorders associated with Alzheimer’s disease (AD) and other neurological disorders, including Huntington’s disease (HD). Moreover, preliminary evidence suggests that certain clinical populations may be prone to exhibit different types of intrusion errors. Methods: We examined the prevalence of two new California Verbal Learning Test-3 (CVLT-3) intrusion subtypes – across-trial novel intrusions and across/within trial repeated intrusions – in individuals with AD or HD. We hypothesized that the encoding/storage impairment associated with medial-temporal involvement in AD would result in a greater number of novel intrusions on the delayed recall trials of the CVLT-3, whereas the executive dysfunction associated with subcortical-frontal involvement in HD would result in a greater number of repeated intrusions across trials. Results: The AD group generated significantly more across-trial novel intrusions than across/within trial repeated intrusions on the delayed cued-recall trials, whereas the HD group showed the opposite pattern on the delayed free-recall trials. Conclusions: These new intrusion subtypes, combined with traditional memory analyses (e.g., recall versus recognition performance), promise to enhance our ability to distinguish between the memory disorders associated with primarily medial-temporal versus subcortical-frontal involvement.

Objectives: The third edition of the California Verbal Learning Test (CVLT-3) includes a new index termed List A versus Novel/Unrelated recognition discriminability (RD) on the Yes/No Recognition trial. Whereas the Total RD index incorporates false positive (FP) errors associated with all distractors (including List B and semantically related items), the new List A versus Novel/Unrelated RD index incorporates only FP errors associated with novel, semantically unrelated distractors. Thus, in minimizing levels of source and semantic interference, the List A versus Novel/Unrelated RD index may yield purer assessments of yes/no recognition memory independent of vulnerability to source memory difficulties or semantic confusion, both of which are often seen in individuals with primarily frontal-system dysfunction (e.g., early Huntington’s disease [HD]). Methods: We compared the performance of individuals with Alzheimer’s disease (AD) and HD in mild and moderate stages of dementia on CVLT-3 indices of Total RD and List A versus Novel/Unrelated RD. Results: Although AD and HD subgroups exhibited deficits on both RD indices relative to healthy comparison groups, those with HD generally outperformed those with AD, and group differences were more robust on List A versus Novel/Unrelated RD than on Total RD. Conclusions: Our findings highlight the clinical utility of the new CVLT-3 List A versus Novel/Unrelated RD index, which (a) maximally assesses yes/no recognition memory independent of source and semantic interference; and (b) provides a greater differentiation between individuals whose memory disorder is primarily at the encoding/storage level (e.g., as in AD) versus at the retrieval level (e.g., as in early HD). (JINS, 2018, 24, 833–841)

Objectives: Cognitive dysfunction from high altitude exposure is a major cause of civilian and military air disasters. Pilot training improves recognition of the early symptoms of altitude exposure so that countermeasures may be taken before loss of consciousness. Little is known regarding the nature of cognitive impairments manifesting within this critical window when life-saving measures may still be taken. Prior studies evaluating cognition during high altitude simulation have predominantly focused on measures of reaction time and other basic attention or motor processes. Memory encoding, retention, and retrieval represent critical cognitive functions that may be vulnerable to acute hypoxic/ischemic events and could play a major role in survival of air emergencies, yet these processes have not been studied in the context of high altitude simulation training. Methods: In a series of experiments, military aircrew underwent neuropsychological testing before, during, and after brief (15 min) exposure to high altitude simulation (20,000 ft) in a pressure-controlled chamber. Results: Acute exposure to high altitude simulation caused rapid impairment in learning and memory with relative preservation of basic visual and auditory attention. Memory dysfunction was predominantly characterized by deficiencies in memory encoding, as memory for information learned during high altitude exposure did not improve after washout at sea level. Retrieval and retention of memories learned shortly before altitude exposure were also impaired, suggesting further impairment in memory retention. Conclusions: Deficits in memory encoding and retention are rapidly induced upon exposure to high altitude, an effect that could impact life-saving situational awareness and response. (JINS, 2017, 23, 1–10)

Decline in executive function has been noted in the prodromal stage of Alzheimer's disease (AD) and may presage more global cognitive declines. In this prospective longitudinal study, five measures of executive function were used to predict subsequent global cognitive decline in initially nondemented older adults. Of 71 participants, 15 demonstrated significant decline over a 1-year period on the Dementia Rating Scale (Mattis, 1988) and the remaining participants remained stable. In the year before decline, the decline group performed significantly worse than the no-decline group on two measures of executive function: the Color-Word Interference Test (CWIT; inhibition/switching condition) and Verbal Fluency (VF; switching condition). In contrast, decliners and non-decliners performed similarly on measures of spatial fluency (Design Fluency switching condition), spatial planning (Tower Test), and number-letter switching (Trail Making Test switching condition). Furthermore, the CWIT inhibition-switching measure significantly improved the prediction of decline and no-decline group classification beyond that of learning and memory measures. These findings suggest that some executive function measures requiring inhibition and switching provide predictive utility of subsequent global cognitive decline independent of episodic memory and may further facilitate early detection of dementia. (JINS, 2012, 18, 118–127)

Schizophrenia is associated with executive dysfunction. Yet, the degree to which executive functions are impaired differentially, or above and beyond underlying basic cognitive processes is less clear. Participants included 145 matched pairs of individuals with schizophrenia (SCs) and normal comparison subjects (NCs). Executive functions were assessed with 10 tasks of the Delis-Kaplan Executive Function System (D-KEFS), in terms of “achievement scores” reflecting overall performance on the task. Five of these tasks (all measuring executive control) were further examined in terms of their basic component (e.g., processing speed) scores and contrast scores (reflecting residual higher order skills adjusted for basic component skills). Group differences were examined via multivariate analysis of variance. SCs had worse performance than NCs on all achievement scores, but the greatest SC-NC difference was that for the Trails Switching task. SCs also had worse performance than NCs on all basic component skills. Of the executive control tasks, only Trails Switching continued to be impaired after accounting for impairments in underlying basic component skills. Much of the impairment in executive functions in schizophrenia may reflect the underlying component skills rather than higher-order functions. However, the results from one task suggest that there might be additional impairment in some aspects of executive control. (JINS, 2010, 17, 000–000)

There is increasing consensus regarding the importance of operationally defining and measuring functional decline in mild cognitive impairment (MCI). However, few studies have directly examined functional abilities in MCI or its presumed subtypes and, to date, reported findings have been discrepant. Nondemented older adults (n = 120) were administered a comprehensive cognitive battery measuring multiple domains as well as a performance-based functional ability measure. Participants were characterized as either cognitively normal, amnestic MCI, or non-amnestic MCI. MCI individuals demonstrated decrements in instrumental activities of daily living (IADL) relative to their cognitively normal counterparts. Specifically, participants with amnestic MCI demonstrated significant decrements in financial management, whereas those with non-amnestic MCI showed poorer performance in abilities related to health and safety. Moreover, decreased functional abilities were associated with decrements in global cognitive functioning but not memory or executive functions in the MCI participants. Finally, logistic regression demonstrated that functional abilities accurately predicted MCI subtype. Results support the need for better delineation of functional decline in MCI. Given the implications of functional status for MCI diagnosis and treatment, the direct assessment of functional abilities is recommended. Results further suggest performance-based IADL assessment may have utility in distinguishing MCI subtypes. (JINS, 2010, 16, 630–639.)

In this study, verbal learning and memory following pediatric closed-head injuries (CHI) using the children's version of the California Verbal Learning Test (CVLT). Participants included 47 children, ages 5–16 yr, with a history of CHI, and 47 matched, noninjured controls. Children with CHI performed more poorly than controls on the CVLT, although their deficits varied qualitatively as a function of injury severity. Those with mild/moderate injuries performed as well as controls on learning trials, but they recalled proportionally fewer words after a delay (although their recognition was intact). Severely injured children demonstrated deficits in learning, delayed recall, and recognition, compared to controls. The groups did not differ in learning characteristics, but children with severe CHI exhibited more intrusions than controls. Pediatric CHI are associated with specific disturbances in verbal learning and memory similar to those of adults with CHI but different from those of children with other developmental and neurological disorders. JINS, 1995, I, 78–87.)

The California Verbal Learning Test was used to characterize the learning and memory impairment in schizophrenia (SC) and to evaluate potential clinical and demographic factors associated with this impairment. SC patients (n = 175) performed worse than normal comparison (NC) subjects (n = 229) on all learning, recall, and recognition memory measures. The most important clinical correlates of these impairments were earlier age of onset, more negative symptoms, and greater anticholinergic medication dosage. SC patients showed a prominent retrieval deficit as indicated by disproportionate improvement when tested in a recognition, rather than a free recall, format. A residual impairment seen with recognition testing suggests a mild encoding deficit as well. In contrast, the relative absence of a storage deficit is suggested by the lack of rapid forgetting. Using a discriminant function analysis that differentiates cortical dementia [i.e., Alzheimer's disease (AD)], subcortical dementia [i.e., Huntington's disease (HD)], and normals, it was found that 5070 of the SC patients were classified as having a subcortical memory profile and 35% were classified as having a normal profile, whereas only 15% were classified as having a cortical memory profile. Although these findings reflect the clinical heterogeneity often found in SC, results suggest that most SC patients demonstrate a pattern of learning and memory impairments that resembles the pattern seen in patients with primary subcortical (specifically striatal) pathology. (JINS, 1995, I, 88–99.)

This study evaluated cognitive set-shifting in 12 patients with focal lesions in the lateral prefrontal cortex (LPC) by examining their performance on the Trail Making Test from the Delis-Kaplan Executive Function System (D-KEFS). Patients with LPC lesions performed significantly worse than controls on the D-KEFS Trail Making Test on the Letter Sequencing, Number-Letter Switching (set-shifting), and Motor Speed conditions. Patients with LPC lesions performed significantly more slowly on the Number-Letter Switching condition even after controlling for performance on the four baseline conditions of the test. In addition, patients with LPC lesions exhibited significantly elevated error rates on the Number-Letter Switching condition. Results suggest that LPC lesions can lead to impaired cognitive set-shifting on a visual-motor sequencing task. (JINS, 2007, 13, 704–709.)

The purpose of this study was to examine the relationships between lobar volumes and set shifting. We studied 101 subjects, including 36 normal controls, 16 patients with probable Alzheimer's disease, 30 patients with frontotemporal dementia (FTD), and 19 patients with semantic dementia (SD), using a shifting paradigm that carefully controlled for component abilities. Subjects were administered two conditions of the Delis–Kaplan Executive Function System (D-KEFS) Design Fluency Test. In the control condition (DF:Control), examinees generated as many unique designs as possible in 60 s by drawing lines connecting only unfilled dots. In the switching condition (DF:Switch), examinees generated designs by drawing lines alternating between filled and unfilled dots. We used BRAINS2 software to generate volumes of the right and left frontal, temporal, and parietal lobes. Partial correlations and multiple regressions showed that, after controlling for Mini-Mental State Examination and DF:Control, only the right and left frontal lobe volumes significantly correlated with the DF:Switch, most clearly in the FTD and SD groups. Follow-up analyses indicated that frontal contributions to shifting were not related to working memory. Results highlight the importance of carefully controlling for component cognitive processes when studying executive functioning. (JINS, 2007, 13, 386–392.)

Response bias reflects the decision rule an individual uses when faced with uncertainty on recognition memory tasks. Recent studies indicate frontal regions may mediate response bias performance. One theory of aging also implicates frontal lobe contributions in age-related cognitive changes. This suggests that frontal lobe changes may mediate response bias in older adults. Consistent with this frontal aging hypothesis, we predicted that response bias would become more liberal with age. Methods: Participants were 181 younger (30–49) and 112 older normal adults (75+) that were part of the California Verbal Learning Test-second edition (CVLT-2) normative sample (total n = 1078). We used parametric measures of discriminability and response bias provided by the CVLT-2 scoring program. Groups were similar in IQ and education. Multi-level regression models were created to examine the effects of moderating variables. The interaction between age and age group significantly predicted response bias. Post hoc analysis indicated that increasing age was associated with more liberal bias in the older but not in the younger group. In the light of reported relationships between frontal regions and both aging and response bias, we hypothesize that frontal changes may be the underlying mechanism explaining the increase in liberal response bias with age. (JINS, 2006, 12, 1–7.)

Recent studies have reported cognitive asymmetries in patients with Alzheimer's disease (AD) and in individuals with apolipoprotein E ε4 (APOE ε4) genotype who are in the preclinical phase of AD. This increased frequency of cognitive asymmetry, typically defined as a significant discrepancy (in either direction) between verbal and spatial abilities, often occurs despite an absence of differences on traditional measures of central tendency (i.e., mean test scores). We prospectively studied the relationship between APOE genotype and two modality-specific executive-function tasks: The Verbal Fluency and Design Fluency tests of the Delis-Kaplan Executive Function System (D-KEFS) in 52 normal functioning older adult participants who were grouped according to the presence (n = 24) or absence (n = 28) of the APOE ε4 allele. Nondemented older adults with the APOE ε4 allele demonstrated a greater frequency of cognitive asymmetric profile on the new switching conditions of the Verbal and Design Fluency measures than the APOE non-ε4 individuals. This study further supports the utility of assessing cognitive asymmetry for the detection of subtle cognitive differences in individuals at-risk for AD, and suggests that dual-task executive function tests (i.e., fluency plus switching) may serve as a useful preclinical marker of AD. (JINS, 2005, 11, 863–870.)

Memory tests that are in a recall format have almost universally measured accuracy in terms of the number of target items reported by the examinee. However, this traditional scoring method can, in certain cases, result in artificially inflated memory accuracy scores. That is, just as a “yes” response bias and high false-positive rate on recognition testing can artificially inflate a patient's hit rate, so, too, a liberal response bias and high intrusion rate on recall testing can artificially inflate a patient's level of target recall. Recognition tests correct for this problem by using a discriminability measure that provides a single score of hit rate relative to false-positive rate; however, recall tests rarely provide a single score of recall accuracy that corrects for intrusion rate. In the present study, we examined the utility of a new recall discriminability measure that analyzes target recall relative to intrusion rate. Patients with Alzheimer's disease (AD) or Huntington's disease (HD) were administered the CVLT–II, which provides both the traditional measure of target recall and a new measure of recall discriminability. The results indicate that the new recall discriminability measure was superior to the traditional level of target recall measure in distinguishing the recall performance of AD and HD patients. Implications of these results for clinical practice and theories of memory disorder in dementia are discussed. (JINS, 2005, 11, 708–715.)

Frontal-lobe epilepsy (FLE), temporal-lobe epilepsy (TLE), and matched-control subjects were administered the Trail Making Test (TMT) of the Delis-Kaplan Executive Function System (D-KEFS; Delis et al., 2001), which assesses set-shifting on a visuomotor sequencing task. Results indicated that patients with FLE were impaired in both speed and accuracy on the switching condition relative to patients with TLE and controls. The two patient groups did not differ from controls on the four baseline conditions of the test, which assess visual scanning, motor speed, number sequencing, and letter sequencing. In addition, seizure-related variables (i.e., age of seizure onset, duration of epilepsy, and seizure frequency) failed to correlate with set-shifting performance in patients with FLE. These results suggest that patients with FLE can be reliably distinguished from those with TLE and control subjects on set-shifting as measured by the DKEFS TMT. (JINS, 2005, 11, 477–481.)

Problem: Inferential reasoning in language involves the ability to deduce information based on context and prior experience. This ability has been generally studied as a right-hemisphere function. Recent research, however, has suggested that inferencing involves anterior regions of both the left and right hemispheres. Methods: We further explored this idea by testing a group of non-aphasic, focal frontal patients (right and left hemisphere) on a new test of inferencing, the Word Context Test. The Word Context Test requires examinees to identify the meaning of a made-up word (e.g., prifa) based on its use in a series of sentences. Findings: Patients with frontal lobe lesions were significantly impaired on this task relative to a group of age- and education-matched controls. Contrary to earlier research focusing on a special role for the right hemisphere in inferencing, there was considerable overlap in performance of right- and left-frontal patients, with right-frontal patients performing better. Conclusions: These findings suggest that inferencing is disrupted following focal frontal injury and have implications for discourse comprehension in non-aphasic patients. (JINS, 2005, 11, 426–433.)

In a recent study, we empirically demonstrated limitations in traditional ways that psychologists have used factor analysis to define cognitive constructs (Delis et al., 2003). Our criticism of factor analysis was not directed at this statistical method per se, but rather at how it has often been employed by psychologists to test cognitive constructs. Specifically, we pointed out shortcomings in using this technique with normal or mixed clinical populations. We argued that the factor-analytic studies of memory tests with normal or mixed clinical populations often yielded solutions in which measures of immediate and delayed memory loaded on the same factor. This particular use of factor analysis can mask important distinctions between critical cognitive functions that have been demonstrated using other research methods, such as experimental manipulations or case studies. We then conducted a factor-analytic study that empirically demonstrated that, whereas immediate and delayed memory measures load on the same factor when using normal or mixed clinical samples, these measures load on separate factors when using a homogenous population of patients with Alzheimer's disease (AD). We drew the conclusion that factor analytic techniques can still be used as one method for exploring conceptual relationships, but only if these methods are used as part of a systematic, programmatic exploration involving separate confirmatory factor analyses using multiple homogenous patient populations. In the first published reply to our study, Larrabee (2003) pointed out other limitations, stating that application of factor-analytic techniques to a single test that yields multiple measures may result in global, simplistic solutions due to method variance, which is the tendency of different variables from the same test to correlate significantly.

Verbal learning and memory (VLM) following pediatric stroke was characterized in a cross-sectional neuropsychological and neuroimaging study of 26 subjects, aged 5 to 17, with a history of pediatric stroke and 26 age, SES, and gender matched orthopedic controls. Further comparisons were made between the VLM profiles of stroke subjects with right versus left hemisphere lesions and early (≤12 months) versus late (>12 months) strokes. Overall, stroke subjects scored significantly lower than control subjects on several VLM indices (California Verbal Learning Test–Children; CVLT–C), as well as on measures of intellectual functioning (IQ) and auditory attention/working memory (Digit Span). Subgroup analyses of the stroke population found no significant differences in VLM, Digit Span, Verbal IQ or Performance IQ when left-hemisphere lesion subjects were compared to right-hemisphere lesion subjects. In contrast, early strokes were associated with significantly fewer words recalled after delay, reduced discriminability (fewer correct hits relative to false positive errors on recognition testing), and relatively worse auditory attention/working memory scores (Digit Span). These findings indicate that pediatric stroke subjects demonstrated more VLM impairment than control subjects, and early strokes were associated with greater recall and recognition deficits. In stark contrast with adult-onset stroke, both left- and right-hemisphere lesions during childhood resulted in similar VLM performance. (JINS, 2004, 10, 742–752.)

Little is known about possible differences in the memory deficits that occur in Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). We compared 24 autopsy-confirmed DLB and 24 age-, education-, and MMSE-matched autopsy-confirmed AD patients on the California Verbal Learning Test (CVLT) and the Wechsler Memory Scale-Revised Logical Memory subtest. The DLB and AD groups were similarly impaired on CVLT Total Learning (Trials 1–5) and Long Delayed Free Recall, but the DLB group demonstrated relative improvement in Savings scores and on recognition testing compared to the AD group. Likewise, the patient groups were equally impaired on Logical Memory immediate and delayed recall, but the DLB group's Saving scores were significantly better than those of the AD patients. These results indicate that while both DLB and AD patients exhibit significant memory impairment, the ability to consolidate information may be less severely impaired in DLB patients than in AD patients. (JINS, 2004, 10, 689–697.)

Cognitive deficits following ventromedial prefrontal damage (VM-PFD) have been elusive, with most studies reporting primarily emotional and behavioral changes. The present case illustrates the utility of a process approach to assessing cognitive deficits following VM-PFD. At age 26, C.D. acquired bilateral VM-PFD, more so in the left frontal region, following a penetrating head injury. Despite exemplary premorbid academic and military performances, his subsequent history suggests dramatic occupational and social changes, reminiscent of Phineas Gage. In fact, lesion analysis revealed similar structural damage to that estimated of Gage. C.D.'s scores on the vast majority of neuropsychological measures were average to superior (e.g., Verbal IQ = 119). However, on several new process measures, particularly those that quantify error rates on multilevel executive function and memory tasks, C.D. exhibited marked impairments. From his pattern of deficits, C.D. appeared to sacrifice accuracy for speed and to adopt liberal response strategies, implicating problems with cognitive inflexibility, impulsivity, and disinhibition. The current findings suggest that VM-PFD may be associated with a wider spectrum of cognitive deficits than previously characterized. (JINS, 2004, 10, 453–465.)