Identification of Subtle Verbal Memory Deficits in Premanifest Huntington Disease Using the California Verbal Learning Test.

BACKGROUND: Verbal memory impairment in individuals with Huntington disease (HD) is well-documented; however, the nature and extent of verbal memory impairment in individuals with premanifest HD (pre-HD) are less understood. OBJECTIVE: To evaluate verbal memory function in individuals with pre-HD by comparing their performance on the California Verbal Learning Test to that of individuals with a clinical diagnosis of HD and that of a demographically similar group of adults with no family history of, or genetic risk for, HD, thereby reducing possible complications of psychiatric difficulties commonly experienced by individuals who are at risk for HD but are gene negative. METHODS: Participant groups included 77 adults with a diagnosis of HD, 23 premanifest gene carriers for HD (pre-HD), and 54 demographically similar, healthy adults. The California Verbal Learning Test-Second Edition (CVLT-II) was used to evaluate the participants' immediate and delayed recall, recognition, learning characteristics, errors, and memory retention. RESULTS: The pre-HD group performed significantly worse than the healthy group, yet significantly better than the HD group, on Short and Long Delay Recall (Free and Cued) and Recognition Discriminability. On Total Immediate Recall, Learning Slope, Semantic Clustering, and Intrusions, the pre-HD group performed similarly to the healthy group and significantly better than the HD group. None of the groups differed in their performance on Repetitions and a measure of retention. CONCLUSIONS: Subtle memory deficits can be observed during the premanifest stage of HD with use of a subset of indices from the CVLT-II.

New Intrusion Analyses on the CVLT-3: Utility in Distinguishing the Memory Disorders of Alzheimer's versus Huntington's Disease.

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.

New Yes/No Recognition Memory Analysis on the California Verbal Learning Test-3: Clinical Utility in Alzheimer's and Huntington's Disease.

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).

Mechanisms of Memory Dysfunction during High Altitude Hypoxia Training in Military Aircrew.

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).

CogSMART Compensatory Cognitive Training for Traumatic Brain Injury: Effects Over 1 Year.

OBJECTIVE: There are very few evidence-based treatments for individuals with mild to moderate traumatic brain injuries. We developed and tested a 12-week, manualized, compensatory cognitive training intervention, Cognitive Symptom Management and Rehabilitation Therapy (CogSMART), which targeted postconcussive symptom management, prospective memory, attention, learning/memory, and executive functioning. The intervention focused on psychoeducation and compensatory strategies such as calendar use, self-talk, note taking, and a 6-step problem-solving method. SETTING: VA Healthcare System. PARTICIPANTS: A total of 50 Veterans with mild to moderate traumatic brain injuries receiving supported employment. DESIGN: Twelve-month randomized controlled trial with participants assigned to receive CogSMART or additional supported employment sessions for the first 12 weeks. Outcome assessments were administered at baseline and 3, 6, and 12 months. MAIN MEASURES: Assessments measured postconcussive symptoms, neuropsychological performance, functional capacity, psychiatric symptom severity, quality of life, and weeks worked during the 12-month trial. RESULTS: Hierarchical linear modeling analyses using all 4 time points demonstrated significant CogSMART-associated reductions in postconcussive symptoms (r = -0.28, P = .026, d = 0.64) and improvements in prospective memory (r = 0.35, P = .031, d = 0.55) and quality of life (r = 0.34, P = .009, d = 1.0). The groups did not differ on weeks worked during the trial. CONCLUSION: CogSMART has the potential to improve postconcussive symptoms, cognitive performance, and self-rated quality of life in individuals with mild to moderate traumatic brain injuries.

Specific measures of executive function predict cognitive decline in older adults.

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.

Source recognition discriminability impairment in Huntington's versus Alzheimer's disease: Evidence from the CVLT-3.

Research suggests that individuals with Huntington's disease (HD) perform better than individuals with Alzheimer's disease (AD) on the California Verbal Learning Test (CVLT) Yes/No Recognition trial. However, those with HD have been shown to have deficits comparable to those with AD on the Source Recognition Discriminability (RD) index (which assesses the ability to distinguish between List A targets and List B distractors), suggesting that HD may involve selective impairment in aspects of yes/no recognition that rely on source memory. However, whether individuals with HD and AD show comparable deficits on Source RD across stages of dementia severity has not been adequately investigated. We examined performance on the CVLT-3 List A vs. List B RD index in individuals with HD or AD and mild or moderate dementia. Among individuals with mild dementia, scores were higher in the HD versus AD group, whereas among individuals with moderate dementia, scores were comparable between the HD and AD groups; this corresponded to differential performance across dementia stages among individuals with HD, but not AD. The present findings suggest that, relative to AD, HD may be associated with disproportionate decline in aspects of yes/no recognition that rely on source memory.

Evaluation of specific executive functioning skills and the processes underlying executive control in schizophrenia.

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.

Cohort differences on the CVLT-II and CVLT3: Evidence of a negative Flynn effect on the attention/working memory and learning trials.

OBJECTIVE: Although cohort effects on IQ measures have been investigated extensively, studies exploring cohort differences on verbal memory tests, and the extent to which they are influenced by socioenvironmental changes across decades (e.g. educational attainment; ethnic makeup), have been limited. METHOD: We examined differences in performance between the normative samples of the CVLT-II from 1999 and the CVLT3 from 2016 to 2017 on the immediate- and delayed-recall trials, and we explored the degree to which verbal learning and memory skills might be influenced by the cohort year in which norms were collected versus demographic factors (e.g. education level). RESULTS: Multivariate analysis of variance tests and follow-up univariate tests yielded evidence for a negative cohort effect (also referred to as negative Flynn effect) on performance, controlling for demographic factors (p = .001). In particular, findings revealed evidence of a negative Flynn effect on the attention/working memory and learning trials (Trial 1, Trial 2, Trial 3, Trials 1-5 Total, List B; ps < .007), with no significant cohort differences found on the delayed-recall trials. As expected, education level, age group, and ethnicity were significant predictors of CVLT performance (ps < .01). Importantly, however, there were no interactions between cohort year of norms collection and education level, age group, or ethnicity on performance. CONCLUSIONS: The clinical implications of the present findings for using word list learning and memory tests like the CVLT, and the potential role of socioenvironmental factors on the observed negative Flynn effect on the attention/working memory and learning trials, are discussed.

Revisiting total recognition discriminability in Huntington's and Alzheimer's disease: New insights from the CVLT-3.

The original and second editions of the California Verbal Learning Test (CVLT) used nonparametric and parametric methods, respectively, to assess Total Recognition Discriminability (RD). In a previous study, we found evidence that the nonparametric formula may be more sensitive than the parametric formula to high false positive (FP) rates and provide more accurate assessments of yes/no recognition in neurodegenerative populations prone to high FP rates, including Alzheimer's disease (AD). In the present study, we extended our investigation to examine the utility of CVLT-3 nonparametric and parametric Total RD indices in the assessment and comparison of yes/no recognition in individuals with Huntington's disease (HD) and AD in mild and moderate stages of dementia. Findings suggested that the CVLT-3 nonparametric Total RD index was more sensitive than the parametric index to HD and AD differences in yes/no recognition across mild and moderate stages of dementia. Additionally, group differences on total FP errors were more closely mirrored by group differences on the nonparametric Total RD index. The present results bolster our previous findings and highlight the utility of examining nonparametric (in addition to parametric) Total RD on the CVLT-3 in assessments of yes/no recognition involving clinical populations prone to high FP rates.

Complex activities of daily living vary by mild cognitive impairment subtype.

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.

Utility of the D-KEFS Color Word Interference Test as an embedded measure of performance validity.

Objective: The D-KEFS Color Word Interference Test (CWIT) is among the most commonly administered measures of verbally mediated processing speed and executive functioning. Previous research suggests that this test may also be sensitive to performance invalidity. We sought to develop new embedded measures of performance invalidity based on multi-condition performance on the CWIT and to evaluate previously proposed embedded measures for performance invalidity on this test.Method: Newly developed and previously proposed embedded measures were evaluated in three samples: a traumatic brain injury (TBI) sample (N = 224) classified into psychometrically-defined performance-valid and performance-invalid subgroups; the D-KEFS normative sample (N = 1,735); and a Parkinson's disease sample (N = 166). To explore the resilience of CWIT cutoffs to the effects of age and neurocognitive impairment, the D-KEFS normative sample was stratified into age groups of 8-19, 20-69, and 70-89 and the Parkinson's disease sample into normal cognition, mild cognitive impairment, and dementia groups.Results: Our newly developed embedded measures derived from within the TBI sample were largely resilient to the effects of age and neurocognitive impairment other than dementia. Overall, a cutoff of ≤18 on the sum of age-corrected scaled scores on all four conditions exhibited the strongest classification accuracy. In contrast, previously proposed cutoffs (Erdodi et al., 2018) produced unacceptable false-positive rates within the TBI sample and generally a high rate of potential false positives in the normative age and clinical groups.Conclusion: Scoring ≤18 on the sum of all conditions on the CWIT appears to be an optimal cutoff for performance invalidity detection in non-demented samples.

The emergence of age-related changes in recognition memory in healthy middle-aged adults using the CVLT-II.

Although age-related memory differences between young and older adults have been well documented, fewer studies have investigated memory changes in middle age. We examined the performance of healthy middle-aged adults (40-55 years of age; n = 32) in relation to healthy young (18-25 years of age; n = 57) and older adults (65+ years of age; n = 55) on variations of recognition discriminability (RD) indices derived from the California Verbal Learning Test-Second Edition (CVLT-II). Middle-aged adults performed significantly worse (ps < .05) than young adults on multiple RD indices that incorporate semantically related distractor items, suggesting memory changes in middle age may be associated with increased susceptibility to semantic interference. Moreover, middle-aged adults performed comparably to older adults across all RD indices, indicating the recognition profile of middle-aged adults on RD indices more closely resembles that of older adults than young adults.

Quantification of five neuropsychological approaches to defining mild cognitive impairment.

OBJECTIVES: Operational definitions of cognitive impairment have varied widely in diagnosing mild cognitive impairment (MCI). Identifying clinical subtypes of MCI has further challenged diagnostic approaches because varying the components of the objective cognitive assessment can significantly impact diagnosis. Therefore, the authors investigated the applicability of diagnostic criteria for clinical subtypes of MCI in a naturalistic research sample of community elders and quantified the variability in diagnostic outcomes that results from modifying the neuropsychological definition of objective cognitive impairment. DESIGN: Cross-sectional and longitudinal study. SETTING: San Diego, CA, Veterans Administration Hospital. PARTICIPANTS: Ninety nondemented, neurologically normal, community-dwelling older adults were initially assessed and 73 were seen for follow-up approximately 17 months later. MEASUREMENTS: Participants were classified via consensus diagnosis as either normally aging or having MCI via each of the five diagnostic strategies, which varied the cutoff for objective impairment and the number of neuropsychological tests considered in the diagnostic process. RESULTS: A range of differences in the percentages identified as MCI versus cognitively normal were demonstrated, ranging from 10-74%, depending on the classification criteria used. A substantial minority of individuals demonstrated diagnostic instability over time and across diagnostic approaches. The single domain nonamnestic subtype diagnosis was particularly unstable (e.g., prone to reclassification as normal at follow up). CONCLUSION: Our findings provide empirical support for a neuropsychologically derived operational definition of clinical subtypes of MCI and point to the importance of using comprehensive neuropsychological assessments. Diagnoses, particularly involving nonamnestic MCI, were variable over time. The applicability and utility of this particular MCI subtype warrants further investigation.

The emergence of cognitive discrepancies in preclinical Alzheimer's disease: a six-year case study.

We present neuropsychological data from an 81-year-old individual who was followed over a six-year period, initially as a healthy control participant. She performed above age-adjusted cutoff scores for impairment on most neuropsychological tests, including learning and memory measures, until the final assessment when she received a diagnosis of probable Alzheimer's disease (AD). Despite generally normal scores on individual cognitive tests, her cognitive profile revealed increasingly large cognitive discrepancies when contrasting verbal versus visuospatial tasks, and complex versus basic-level tasks. The present case provides intriguing evidence that cognitive-discrepancy measures could improve our ability to detect subtle changes in cognition at the earliest, preclinical stages of AD.

Recall and Recognition Discriminability in Parkinson's Disease and Huntington's Disease.

BACKGROUND: Parkinson's disease (PD) and Huntington's disease (HD) are two neurodegenerative diseases affecting frontal-striatal function and memory ability. Studies using the original California Verbal Learning Test (CVLT) to examine recall and recognition abilities between these groups have produced mixed findings. Some found that individuals with HD demonstrate worse recall and recognition than those with PD, whereas others reported comparable performance. OBJECTIVE: We utilized multiple indices of recall and recognition discriminability, provided by the second and third editions of the CVLT (CVLT-II and CVLT-3, respectively), that allow for a more thorough assessment of more nuanced aspects of verbal memory function. METHODS: We examined differences between individuals with PD (n = 72) and those with HD (n = 77) on CVLT-II indices of recall discriminability (immediate, short delay free and cued, long delay free and cued) and recognition discriminability (total, source, semantic, and novel) using standardized scores while controlling for education and Dementia Rating Scale-2 scores. RESULTS: The HD group performed significantly worse than the PD group on all measures of recall and recognition discriminability (ps < 0.05), and group differences were associated with large Cohen's d effect sizes. CONCLUSIONS: Our findings suggest that individuals with HD are more impaired than individuals with PD in more nuanced aspects of recall and recognition memory function. These CVLT indices yield more thorough assessments of recall and recognition memory function and have the potential to improve efforts to characterize and distinguish profiles of memory loss in different neurodegenerative populations, including PD and HD.

Discriminant validity and neuroanatomical correlates of rule monitoring in frontotemporal dementia and Alzheimer's disease.

Despite the predominant frontal neuropathology of frontotemporal dementia (FTD), traditional measures of executive functioning do not reliably distinguish FTD from Alzheimer's disease (AD). Performance monitoring is an executive function that is associated with frontal lobe integrity and may be disrupted in FTD. The current study adopted a component process approach to evaluate the discriminant validity and neuroanatomical correlates of performance monitoring (i.e., rule monitoring) during an executive spatial planning task. Forty-four participants with FTD, 30 with AD, and 27 healthy comparison (HC) subjects completed the Delis-Kaplan Executive Function System (D-KEFS) Tower task. A subset of patients underwent structural magnetic resonance imaging to obtain regional measures of cortical volumes. FTD and AD groups demonstrated significantly poorer overall achievement scores on the Tower test relative to the HC sample, but did not differ from one another. In contrast, the FTD group committed significantly more rule violation errors than both HC and AD groups, indicating poorer performance monitoring. In addition, poorer overall achievement correlated with smaller brain volumes in several regions, including bilateral frontal and parietal regions, whereas an increased number of rule violations correlated specifically with decreased bilateral frontal volume. Both left and right frontal volumes remained significant predictors of rule violation errors after controlling for the contribution of overall achievement on the task and all other brain regions. Findings are consistent with literature implicating the frontal lobes in performance monitoring and highlight the importance of characterizing the component processes of performance failures in the cognitive assessment of FTD and AD.

Cognitive discrepancies versus APOE genotype as predictors of cognitive decline in normal-functioning elderly individuals: a longitudinal study.

OBJECTIVES: Cognitive-discrepancy analysis has been shown to be a useful technique for detecting subtle cognitive deficits in normal-functioning elderly individuals who are genetically at-risk for Alzheimer disease (AD). However, studies that have used cognitive-discrepancy measures to date have used retrospective or cross-sectional designs, and the utility of this approach to predict cognitive decline has not been examined in a prospective investigation. DESIGN: Longitudinal study. SETTING: San Diego, CA, Veterans Administration Hospital. PARTICIPANTS: Twenty-four normal-functioning elderly individuals participated in the study, with 16 subjects exhibiting no change in their Dementia Rating Scale (DRS) scores over an 1-year period (Stable Group), and 8 subjects exhibiting a decline in DRS scores over the 1-year period (Decline group). MEASUREMENTS: A cognitive-discrepancy measure isolating cognitive switching was computed that contrasted performance on a new higher-level task of executive functioning (a Stroop/Switching measure) relative to a composite measure of lower-level Stroop conditions. RESULTS: a) In the year before their cognitive changes, the Decline group exhibited a significantly larger cognitive-discrepancy (Stroop/Switching versus lower-level Stroop conditions) score compared with a control (Stable) group; and b) the cognitive-discrepancy measure was superior to APOE genotype in predicting DRS decline. CONCLUSION: Cognitive-discrepancy analysis isolating a component executive function ability not only seems to be a useful tool for identifying individuals at risk for cognitive deficits, but also shows promise in predicting individuals who may show subtle cognitive decline over time.

Refining CVLT-II recognition discriminability indices to enhance the characterization of recognition memory changes in healthy aging.

The present study examined age-related differences on the four false-positive (FP) error subtypes found on the California Verbal Learning Test-Second Edition yes/no recognition memory trial and the influence of these subtypes on source and novel recognition discriminability (SoRD and NRD, respectively) index calculations. Healthy older (n = 55) adults generally made more FP errors than healthy young adults (n = 57). Accordingly, older adults performed worse than young adults on all SoRD and NRD indices. However, the manner in which FP error subtypes were incorporated into SoRD and NRD index calculations impacted the magnitudes of observed differences between and within the two age groups on SoRD and NRD indices. The present findings underline the importance of examining FP errors in assessments of recognition memory abilities, and using more refined indices of recognition discriminability to further elucidate the nature of age-related recognition memory impairment.

Apolipoprotein E and traumatic brain injury in a military population: evidence of a neuropsychological compensatory mechanism?

OBJECTIVE: Although research has implicated the apolipoprotein E (APOE) epsilon-4 genotype as having a negative effect on neuropsychological outcomes following traumatic brain injury (TBI), the potentially negative role of the epsilon4 allele on TBI outcomes has recently been challenged. In light of this debate, the present study served to examine the role of APOE genotype on neuropsychological outcomes approximately 1 month following mild to moderate TBI in a military population. Because of the well documented role of the APOE-epsilon4 allele in increasing the risk of Alzheimer's disease, we predicted that persons with the APOE-epsilon4 genotype would display relatively greater deficits in cognition than their non-epsilon4 counterparts. METHODS: 78 participants were consecutively recruited following a mild to moderate TBI and were divided into two groups based on the presence or absence of an APOE epsilon4 allele. Groups were comparable on demographic characteristics and psychosocial outcomes. Participants were administered a comprehensive neuropsychological battery. RESULTS: Analyses revealed comparable performances on most neuropsychological measures and better performances by epsilon4 carriers on select measures of attention, executive functioning and episodic memory encoding. Furthermore, differences remained after accounting for the effects of TBI severity. CONCLUSIONS: Evidence from these analyses supports current literature refuting the notion of relatively poorer neuropsychological functioning associated with the APOE-epsilon4 genotype among young adult participants shortly following mild or moderate brain injury. Neuropsychological performance differences by APOE genotype following TBI are discussed in terms of the importance of considering severity of injury, timing of postinjury assessment and possible neurocognitive compensatory mechanisms.