Operationalization of the updated diagnostic algorithm for classifying HIV-related cognitive impairment and dementia.

BACKGROUND: This study applies the updated HIV-Associated Neurocognitive Disorders (HAND) diagnostic algorithm. METHODS: Participants were 210 HIV-infected-adults, classified using proposed HAND criteria: HIV-Associated Dementia (HAD), Mild Neurocognitive Disorder (MND), Asymptomatic Neurocognitive Impairment (ANI). RESULTS: The algorithm yielded: normal = 32.8%, ANI = 21.4%, MND = 34.3%, and HAD = 11.4%. Normal participants performed superior to HAND-defined participants on cognition, and HAD participants performed more poorly on global cognition and executive functioning. Two distinct subgroups of interest emerged: (1) functional decline without cognitive impairment; (2) severe cognitive impairment and minimal functional compromise. CONCLUSIONS: The algorithm discriminates between HIV-infected cognitively impaired individuals. Diagnosis yields two unique profiles requiring further investigation. Findings largely support the algorithm's utility for diagnosing HIV-cognitive-impairment, but suggest distinct subsets of individuals with discrepant cognitive/functional performances that may not be readily apparent by conventional application of HAND diagnosis.

DHEAS and POMS measures identify cocaine dependence treatment outcome.

UNLABELLED: Early attrition is a significant problem in the treatment of cocaine dependence, but it is unclear why some patients succeed in treatment while others relapse or drop out of treatment without a demonstrated relapse. The goal of this study was to determine whether baseline levels of select hormones, including the adrenal hormone and excitatory neurosteroid dehydroepiandrosterone sulfate (DHEAS), would distinguish between treatment outcome groups. Based on the literature, completion of 90 days of treatment was established as a key outcome variable. METHODS: Quantitative urine levels of the cocaine metabolite benzoylecgonine (BE) and other substance of abuse analytes, plasma levels of DHEAS, DHEA, cortisol, and prolactin, and the profile of mood states (POMS) were serially measured in 38 male cocaine-dependent (DSM-IV) patients and in 28 controls of similar gender and age over a six month study. Exclusion criteria for the patients and controls included Axis I mood, anxiety or psychotic disorders. The patients could not manifest substance dependence except to cocaine. The patients and controls received remuneration for urine and blood collection. Blood samples for hormone levels were obtained between 8 and 10 a.m. on days 1, 14 and 21 of a 21-day inpatient treatment program and throughout 6 months of outpatient study visits at 45-day intervals. RESULTS: Attrition from treatment and study appointments occurred predominately at the junction between inpatient and outpatient programs. Forty percent of patients made the transition to outpatient treatment and remained abstinent and in treatment for a median of 103 days (ABST). Forty-two percent of patients dropped out of treatment during the inpatient stay or never returned after completing the inpatient program (DO) and 18% had a documented relapse either during, or within the first week after, the inpatient stay (REL). POMS total scores were elevated at treatment entry for both the ABST and DO groups. Plasma DHEAS levels in the DO patients were decreased compared to controls and increased in the ABST patients. POMS total scores for the REL patients at baseline were at control levels. Baseline cortisol levels were not statistically different between the outcome groups, though they were elevated for all cocaine patient groups. When treatment outcome was collapsed into whether patients completed (ABST) or did not complete 90 days of treatment (90N), ABST plasma DHEAS and cortisol were significantly elevated compared to the 90N patients and controls across the first 3 weeks of cocaine withdrawal. CONCLUSIONS: At treatment entry, each of the three patient outcome groups was identified by levels of circulating DHEAS and distressed mood. In the ABST patients, distressed mood during withdrawal may have been mitigated through antidepressant-like actions of enhanced endogenous DHEAS activity, thus contributing to improved abstinence and treatment retention. Patients, such as the DO group, with high levels of distressed mood at treatment entry and low DHEAS levels may benefit from adjunctive pharmacotherapy that targets DHEAS and POMS measures. Patients, such as the REL group, who lack distressed mood at treatment entry, may require intense application of motivational approaches plus residential treatment.

Cognitive impairment in euthymic bipolar patients with and without prior alcohol dependence. A preliminary study.

BACKGROUND: Few studies of the neurocognitive performance of patients with bipolar disorder have been performed while patients are in the euthymic state. METHODS: Twenty-five euthymic bipolar patients (12 with and 13 without a history of alcohol dependence) were compared with 22 normal control subjects on a neuropsychological test battery assessing a range of cognitive domains. The relationship between subjects' neurocognitive performance and the course-of-illness variables (lifetime episodes and duration of mania, depression, or both), as well as current lithium level, was determined. RESULTS: The results indicated differences across the groups, with the bipolar patients with and without alcohol dependence performing more poorly than controls on tests of verbal memory. Furthermore, bipolar subjects with a history of alcohol dependence had additional decrements in executive (i.e., frontal lobe) functions when compared with controls. For subjects in the bipolar group, lifetime months of mania and depression were negatively correlated with performance in verbal memory and several executive function measures. CONCLUSIONS: Our findings support the presence of persistent neurocognitive difficulties in patients with long-standing bipolar disorder who are not in the psychiatrically acute state or who are suffering the effects of alcohol abuse and suggest that there may be an aggregate negative effect of lifetime duration of bipolar illness on memory and frontal or executive systems.

Declarative and procedural memory functioning in abstinent cocaine abusers.

BACKGROUND: We determined the nature and recovery of procedural and declarative memory functioning in a cocaine-abusing cohort in the 45-day period following use. METHODS: Thirty-seven cocaine abusers and 27 control subjects were administered the following memory and mood measures: California Verbal Learning Test, recall of the Rey-Osterrieth Complex Figure Test, Pursuit Rotor Task, and Profile of Mood States at 4 visits (within 72 hours of admission and at 10, 21, and 45 days following abstinence). RESULTS: Analysis of performance on the Rey-Osterrieth Complex Figure Test revealed that both groups improved in their recall over repeated administrations, though the control group recalled significantly more of the information than cocaine subjects during the 45-day interval. Results for the California Verbal Learning Test indicated improved learning for both subject groups over time, but no group x time interaction. On the Pursuit Rotor Task, cocaine abusers improved their performance at a faster rate than controls at visit 1. At day 45 (visit 4), cocaine abusers again showed improvement on the Pursuit Rotor Task, whereas controls demonstrated a relative plateau in rate of learning. CONCLUSIONS: This study documented a lasting detrimental effect on a sensitive nonverbal declarative memory task in cocaine-dependent subjects following abstinence of 45 days. In contrast, abstinence from cocaine during this 45-day period was associated with sustained improvement on a motor learning test in the cocaine abusers relative to controls.

Highly active antiretroviral treatment in HIV infection: benefits for neuropsychological function.

OBJECTIVES: To determine whether highly active antiretroviral therapy (HAART) is associated with reduced HIV-associated neuropsychological impairment. DESIGN: Cross-sectional analysis in a natural history study of adaptation to HIV/AIDS. METHOD: A sample of 130 homo-/bisexual men with HIV/AIDS (mean age, 41 years; 42% non-white) were evaluated with a neuropsychological battery assessing attention, concentration, psychomotor speed, learning, memory and executive function. Subjects taking HAART were compared with those not taking HAART on demographics, CD4 cell count, viral load, scores on individual neuropsychological tests and proportion with neuropsychological impairment. RESULTS: Sixty-nine (53%) subjects were taking HAART, and 48 (37%) were neuropsychologically impaired. Subjects taking HAART had lower mean CD4 cell counts than those not taking HAART (254 versus 342 x 10(6)/l; P < 0.05), although they were more likely to have undetectable viral load (42 versus 20%; P < 0.01) and were less likely to be neuropsychologically impaired (22 versus 54%; P < 0.0001). Subjects taking HAART performed significantly better on tests of attention, concentration, learning, memory, and psychomotor speed. After excluding subjects with potential non-HIV confounders of neuropsychological function, those without neuropsychological impairment had significantly lower mean viral load levels and were more likely to have undetectable viral load than those with impairment. CONCLUSION: These preliminary findings suggest that HAART benefits neuropsychological function through the reduction of viral load.

Declarative and procedural memory in bipolar disorder.

BACKGROUND: Memory function is an important but under researched area for neuropsychological investigation in persons with bipolar disorder. Previous studies have reported cognitive deficits on tasks of declarative memory in bipolar patients in the euthymic state. METHODS: This study extended these findings by investigating declarative as well as procedural learning and memory in bipolar patients (with and without alcohol abuse) who were examined in the euthymic state. The California Verbal Learning Test, Star Mirror Tracing Task, Pursuit Rotor Task, American National Adult Reading Test, and the Vocabulary Subtest of the WAIS-R, were administered to bipolar patients and control subjects by researchers who were blind to the subject's group. RESULTS: Bipolar patients performed worse than control subjects on a measure of declarative memory (California Verbal Learning Test) but did not differ from the performance of control subjects on either of the two procedural learning tasks (Pursuit Rotor Task and Star Mirror Task). CONCLUSIONS: These results suggest disturbed function of temporal lobe, but not basal ganglia, structures in persons with bipolar disorder.

Hippocampal and anterior cingulate activation deficits in patients with geriatric depression.

OBJECTIVE: The authors assessed frontotemporal function in patients with geriatric depression, a debilitating and increasingly prevalent disorder that has not been examined with brain activation paradigms. METHOD: Six depressed elderly patients and five healthy comparison subjects underwent high-sensitivity [(15)O]H(2)O positron emission tomography scans during a paced word generation task and a resting condition. RESULTS: Bilateral activation deficits were noted in the dorsal anterior cingulate gyrus and hippocampus of the depressed geriatric patients relative to the comparison subjects. Patients had memory deficits that correlated with lower hippocampal activity during both rest and activation. CONCLUSIONS: These initial findings suggest that hippocampal and dorsal anterior cingulate hypoactivation may constitute contributing neural substrates of geriatric depression. They also suggest that hippocampal dysfunction is related to the memory dysfunction characteristic of this disorder.

Cortical abnormalities associated with subcortical lesions in vascular dementia. Clinical and position emission tomographic findings.

OBJECTIVE: To examine the effects of subcortical lesions on cortical metabolic rate and clinical symptoms in patients with vascular dementia. METHOD: Eleven elderly patients with vascular dementia who demonstrated no lesion involving the cerebral cortex on magnetic resonance imaging underwent 18F-fluorodeoxyglucose positron emission tomography to assess global cortical metabolism and metabolic activity in each cortical lobe. Subcortical lesions on magnetic resonance imaging (periventricular hyperintensities, deep white matter hyperintensities, and subcortical lacunar infarcts) were measured using a graded scale of severity. Cognitive and noncognitive symptoms were assessed with the Neurobehavioral Rating Scale. RESULTS: Reduced cortical metabolism was generally associated with the severity of subcortical pathologic changes, but there was substantial heterogeneity in the relationship between subcortical lesions and cortical metabolic activity. Mean global cortical metabolism was lower in patients with periventricular hyperintensities in anterior subcortical regions than in those without such lesions. The metabolic rate in the frontal cortex was lower in patients with a lacunar infarct of the basal ganglia or thalamus than in those without. Neurobehavioral Rating Scale total score, the Verbal Output Disturbance factor score, and the Anxiety/Depression factor score were correlated with the severity of white matter lesions. CONCLUSIONS: Cortical metabolic dysfunction is related to ischemic subcortical lesions in patients with vascular dementia. Metabolism in the frontal cortex may be particularly dependent on pathologic alterations of subcortical nuclei. Anxiety, depression, and the overall severity of neuropsychiatric symptoms in vascular dementia are associated with the extent of white matter ischemia.

Cognitive performance after progression to AIDS: a longitudinal study from the Multicenter AIDS Cohort Study.

OBJECTIVE: To describe changes in cognitive functioning before and after development of an acquired immune deficiency syndrome (AIDS)-defining illness or CD4+ lymphocyte count < 200/mm3 in participants in the Multicenter AIDS Cohort Study. METHODS: The study population included participants who either were diagnosed with an AIDS-defining illness (n = 52) or had at least one measurement of CD4+ count < 200/mm3 (n = 57) and who had at least four neuropsychological (NP) evaluations, two or more before and two or more after the AIDS diagnosis. A group of subjects with clinical diagnosis of dementia (n = 29) was also included for comparison. The NP test battery included measures of attention, memory, constructional abilities, and psychomotor speed. Longitudinal data analysis, using the generalized estimating equation, was performed separately for each NP measure. Time was measured in months from the date of clinical AIDS or CD4+ < 200/mm3. RESULTS: Before AIDS< the dementia group showed significant decline (slope different from zero) only on measures of psychomotor speed. For all other measures, there was no evidence of decline in performance before AIDS for the other groups. After development of AIDS, the group with clinical AIDS showed significant decline on psychomotor speed but none on the other cognitive measures. The group with CD4+ < 200/mm3 did not show significant decline on any of the cognitive measures after AIDS. As expected, the dementia group showed significant decline on all measures. Sensory neuropathy was associated with a significant decline in performance on measures of psychomotor speed after AIDS. Antiretroviral therapy was not associated with any measurable changes in NP performance. CONCLUSION: These results are consistent with previous findings showing no significant decline in cognitive functions before AIDS, unless overt dementia is present, and no decline in immunosuppressed subjects who have had no AIDS-defining illness. By contrast, in subjects who have developed clinical AIDS, there is mild decline in fine motor skills but no significant change in other cognitive domains.

The relationship between age and cognitive impairment in HIV-1 infection: findings from the Multicenter AIDS Cohort Study and a clinical cohort.

Previous studies have identified age as a risk factor for many neurologic disorders, and a "cerebral reserve" factor has been postulated to explain these findings. This study examined whether age represents a risk factor for HIV-1-related neuropsychological dysfunction. Subjects for study 1 were primarily asymptomatic seropositive (n = 1,066) and seronegative (n = 1,004) nonelderly male community volunteers who completed neuropsychological and reaction time measures. Data analyses revealed a significant effect for age on reaction time and timed neuropsychological measures, but no interaction between age and serostatus. Study 2, employing a similar neuropsychological battery, consisted of 76 seropositive men (29 over age 55) recruited from community outpatient clinics and 47 seronegative controls. We found serostatus and age to have main effects on a number of measures, but a trend for an effect of age-serostatus interaction on only one measure.

Neuropsychological performance in HIV-1-infected homosexual men: The Multicenter AIDS Cohort Study (MACS)

We administered a battery of standardized neuropsychological measures to assess cognitive functions in a group of 769 HIV-1 seronegative, 727 asymptomatic HIV-1 seropositive (CDC Groups 2 and 3), and 84 symptomatic HIV-1 seropositive (CDC Group 4) homosexual/bisexual men enrolled in the Multicenter AIDS Cohort Study (MACS). Measures included tests of attention, memory, and psychomotor speed. Comparison of group means revealed significant differences in performance between HIV-1 seronegative and symptomatic HIV-1 seropositive subjects on measures of memory and on measures with strong motor and psychomotor timed components. These findings support the sensitivity of these neuropsychological instruments for detecting cognitive changes that may be related to HIV-1, and are consistent with other reports of neuropsychological abnormalities in symptomatic HIV-1-infected individuals. Asymptomatic seropositive men, on the other hand, did not differ significantly from seronegative subjects on any of the neuropsychological measures. Only 5.5% of the asymptomatic HIV-1 seropositive men showed abnormal performance on individual tests. This proportion did not differ significantly from that of seronegative controls. Further, among asymptomatic seropositive subjects, we found no statistically significant differences as a function of duration of HIV infection or level of immune system functioning. Thus, results from this study support the hypothesis that the frequency of neuropsychological abnormalities in asymptomatic HIV-1-infected homosexual men is low, and not statistically different from that of seronegative controls.

Effects of acute smoked marijuana on complex cognitive performance.

Although the ability to perform complex cognitive operations is assumed to be impaired following acute marijuana smoking, complex cognitive performance after acute marijuana use has not been adequately assessed under experimental conditions. In the present study, we used a within-participant double-blind design to evaluate the effects acute marijuana smoking on complex cognitive performance in experienced marijuana smokers. Eighteen healthy research volunteers (8 females, 10 males), averaging 24 marijuana cigarettes per week, completed this three-session outpatient study; sessions were separated by at least 72-hrs. During sessions, participants completed baseline computerized cognitive tasks, smoked a single marijuana cigarette (0%, 1.8%, or 3.9% Delta(9)-THC w/w), and completed additional cognitive tasks. Blood pressure, heart rate, and subjective effects were also assessed throughout sessions. Marijuana cigarettes were administered in a double-blind fashion and the sequence of Delta(9)-THC concentration order was balanced across participants. Although marijuana significantly increased the number of premature responses and the time participants required to complete several tasks, it had no effect on accuracy on measures of cognitive flexibility, mental calculation, and reasoning. Additionally, heart rate and several subjective-effect ratings (e.g., "Good Drug Effect," "High," "Mellow") were significantly increased in a Delta(9)-THC concentration-dependent manner. These data demonstrate that acute marijuana smoking produced minimal effects on complex cognitive task performance in experienced marijuana users.

Multidimensional risk assessment versus age as criterion for retirement of airline pilots.

OBJECTIVE: To determine whether airline pilots over the age of 60 pose a hazard to aviation safety and whether risk assessment could replace age-based retirement. DATA SOURCES: A computer-assisted literature search (MEDLINE), expert consultation, and government reports. STUDY SELECTION: Original studies on flight performance and pilot age; sudden incapacitation, neuropsychological testing, and/or medication use in pilots; and/or non-invasive testing for predicting sudden death or stroke in asymptomatic subjects. DATA EXTRACTION: Pertinent results and methods data were abstracted from the 49 included studies. DATA SYNTHESIS: No study on aircraft accidents or pilot performance has shown an increased accident risk for over-60-year-old pilots. Normal age-related cognitive changes probably have minimal impact on aviation safety up to age 70, given above average health, education, and experience in airline pilots. Cognitive tests have not been validated for predicting flight performance safety, but they can detect early stages of cognitive disease. Cardiovascular incapacitation risk increases with age, but risk factor profiles and non-invasive tests could identify pilots with non-acceptable risk. CONCLUSIONS: An improved medical certification test could identify those pathologic conditions that might occur more frequently in older subjects. If pilots also underwent adequate performance testing, a gradual increase of the retirement age to approximately age 70 would seem justified. In the future, a longitudinal database should be established to validate medical tests for their ability to predict a pilot's accident risk. Using individual pilots as their own controls might be more sensitive than using population-based norm values. Progress in this field would advance medical assessment for other groups such as air traffic controllers or automobile drivers.

Diffusion tensor imaging of patients with HIV and normal-appearing white matter on MR images of the brain.

BACKGROUND AND PURPOSE: HIV enters the CNS early in the course of infection and produces neuropsychiatric impairment throughout the course of illness, which preferentially affects the subcortical white matter. The development of a neuroimaging marker of HIV may allow for the earliest detection of cognitive impairment. The purpose of this study was to determine whether MR diffusion tensor imaging can detect white matter abnormalities in patients who have tested positive for HIV. METHODS: Ten patients with HIV (eight men and two women; mean age, 42 years) underwent MR imaging of the brain with MR diffusion tensor imaging, which included routine fluid-attenuated inversion recovery and fast spin-echo T2-weighted imaging. Diffusion constants and anisotropy indices were calculated from diffusion tensor maps. Peripheral viral load, Centers for Disease Control staging, and cluster of differentiation 4 levels were determined. RESULTS: All patients had normal results of MR imaging of the brain, except for mild atrophy. Four of 10 patients had undetectable viral loads. These patients were receiving highly active antiretroviral therapy. The diffusion constant and anisotropy were normal. Four of 10 patients had viral loads between 10,000 and 200,000. Diffusion anisotropy in the splenium and genu was significantly decreased (P < .02). The diffusion constant of the subcortical white matter was elevated in the frontal and parietooccipital lobes (11%). Two of 10 patients had viral loads >400,000. Anisotropy of the splenium was half normal (P < .0004) and of the genu was decreased 25% (P < .002). The average diffusion constant was diffusely elevated in the subcortical white matter. CONCLUSION: Calculating the diffusion constant and anisotropy in the subcortical white matter and corpus callosum in patients with HIV detected abnormalities despite normal-appearing white matter on MR images and nonfocal neurologic examinations. Patients with the highest diffusion constant elevations and largest anisotropy decreases had the most advanced HIV disease. Patients with the lowest viral load levels, who had normal anisotropy and diffusion constants, were receiving highly active antiretroviral therapy.

Neuropsychological deficits in abstinent cocaine abusers: preliminary findings after two weeks of abstinence.

Sixteen subjects hospitalized for treatment of cocaine dependence were administered a battery of neuropsychological tests within 72 h of last cocaine use and again approximately 2 weeks later. Twenty-one non-cocaine using control subjects, matched for age, gender, ethnicity and education, also received neuropsychological testing. Abstinence from mood altering substances during the 2-week study period was verified for both groups on three occasions using quantitative urine analysis. The results suggest that recent cocaine use is associated with impairment in memory, visuospatial abilities, and concentration during the acute phase of withdrawal, independent of withdrawal-related depression. Furthermore, many of these deficits appear to persist at least 2 weeks beyond cessation of cocaine use.

Hand preference in homosexual men.

The present study examined the distribution of hand preference and its relationship to immune system functioning and performance on neuropsychological tests in a sample of 993 homosexual men from the Multicenter AIDS Cohort Study comprising 502 HIV-1 seronegatives, 436 asymptomatic HIV-1 seropositives, and 55 men with diagnoses of AIDS or AIDS Related Complex. The prevalence of left-handedness in all of the groups (13.1-14.5%) was consistent with prior published reports of prevalent left-handedness in the general population. The distribution of hand preference scores (on a 5-item self-report questionnaire) was J-shaped and shifted to the right as in the general population. There were no differences between right- and left-handers in the immune system parameter of CD4 counts, nor was there any increase of self-reported allergies among the left-handers. We found a significantly larger number of 'outliers' on the neuropsychological measures for left-handers than for right-handers, both for HIV-1 seronegatives and seropositives. These results failed to replicate Lindesay's (1987) report of a leftward shift in manual preference among homosexual men, and failed to support Geschwind and Galaburda's (1985b) hypothesis of a link between homosexuality, handedness and autoimmune disorder. The differences between right- and left-handers on neuropsychological measures, independent of HIV-1 serostatus, are discussed in terms of Satz's (1972) model of pathological left-handedness.

Electroencephalographic coherence in acquired immune deficiency syndrome.

We studied a quantitative electroencephalographic (EEG) measure, coherence, in 28 patients with acquired immune deficiency syndrome (AIDS) and 56 uninfected volunteers. Compared with uninfected subjects, AIDS patients had increased coherence in the 6- to 10-Hz band. The largest increases in coherence were between frontal and occipital regions and between temporal and frontal regions. Coherence within contiguous regions was less affected. Eight of the 28 AIDS patients (29%) had clinically abnormal EEG findings, compared with four of the 56 uninfected control subjects (7%). Among the AIDS patients, 12 had normal neuropsychological performance, nine had mild impairment, and six had moderate impairment. Coherence was increased in each subgroup of AIDS patients, including those with normal neuropsychologic performance and/or normal clinical EEG results. AIDS patients were then classified by quantitative EEG power in frontal head regions as "abnormal" (the upper third of patients) or "normal" (the remainder). Increased coherence was found among both groups. Because the development of abnormal neuropsychological performance or a clinically abnormal EEG examination indicates relatively advanced central nervous system disease, alterations in specific coherence measures may detect subclinical effects of the human immunodeficiency virus on brain function before other changes are evident.

Some putative cognitive precursors in subjects hypothesized to be at-risk for dementia.

Virtually no data exists on the early cognitive precursors of dementia, primarily SDAT. This paper presents preliminary cross-sectional data on two elderly groups hypothesized to be at risk for SDAT and a well group matched individually on age, education and gender. The neuropsychological results, based on factor scores and individual t-test comparisons, revealed significant differences between the well group and the two at risk groups, each of which revealed a different pattern of cognitive impairment (specific vs. general). These results stimulated a number of hypotheses concerning the early precursors of SDAT that will be tested in the annual follow-up investigation of these subjects.

Methodologic issues in neuropsychological research with HIV-spectrum disease.

Conflicting data have emerged from the initial studies of the neuropsychogical sequelae of human immunodeficiency virus (HIV) infection. This paper reviews key methodologic issues that must be addressed when embarking upon new research on the neuropsychology of HIV spectrum disease. Finally, suggestions are given for methodologic pitfalls to be avoided when conducting or interpreting research in this domain.

Have we forgotten the base rate problem? Methodological issues in the detection of distortion.

The search for valid and reliable methods of detecting malingering and distortion has become an increasingly important task for forensic psychologists and neuropsychologists. This report highlights several important methodological issues commonly observed in research on the prediction of malingering. The choice of indices for determining optimal cutoff scores on the utility of existing measures, the impact of base rates of malingering on the accuracy of prediction models, the incremental accuracy of combining multiple measures, and the relationship of test validity to the interpretation of data are described with regard to the prediction of malingering on neuropsychological tests. These methodological concerns are discussed in reference to several recent publications assessing the utility of various methods for the detection of malingering.