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.

Discrepancies between self-report and objective measures for stimulant drug use in HIV: cognitive, medication adherence and psychological correlates.

While it has long been recognized that self-reported drug use may be at variance with objectively obtained evidence such as urine toxicology assays, few studies have explored the behavioral correlates of such discrepancies. Here we compared self-reported and objective measures of stimulant drug use for 162 HIV infected individuals and identified a sub-group with discrepancies between data obtained via the two methods. Results showed poorer neurocognitive performance (attention, learning/memory) and lower medication adherence rates for the discrepant group as compared to those who either acknowledged their drug use or accurately denied recent stimulant use. Using the Millon Clinical Multiaxial Inventory-III, it was also found that those in the discrepant group were more hesitant to reveal psychopathology. Comparisons of self-reported and objectively measured medication adherence data are also discussed.

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.

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.

Medication adherence among HIV+ adults: effects of cognitive dysfunction and regimen complexity.

BACKGROUND: Although the use of highly active antiretroviral therapy in the treatment of HIV infection has led to considerable improvement in morbidity and mortality, unless patients are adherent to their drug regimen (i.e., at least 90 to 95% of doses taken), viral replication may ensue and drug-resistant strains of the virus may emerge. METHODS: The authors studied the extent to which neuropsychological compromise and medication regimen complexity are predictive of poor adherence in a convenience sample of 137 HIV-infected adults. Medication adherence was tracked through the use of electronic monitoring technology (MEMS caps). RESULTS: Two-way analysis of variance revealed that neurocognitive compromise as well as complex medication regimens were associated with significantly lower adherence rates. Cognitively compromised participants on more complex regimens had the greatest difficulty with adherence. Deficits in executive function, memory, and attention were associated with poor adherence. Logistic regression analysis demonstrated that neuropsychological compromise was associated with a 2.3 times greater risk of adherence failure. Older age (>50 years) was also found to be associated with significantly better adherence. CONCLUSIONS: HIV-infected adults with significant neurocognitive compromise are at risk for poor medication adherence, particularly if they have been prescribed a complex dosing regimen. As such, simpler dosing schedules for more cognitively impaired patients might improve adherence.

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.

Neuropsychiatric aspects of HIV infection among older adults.

Treatment advances such as the advent of highly active antiretroviral therapy (HAART) have translated into greater life expectancy for HIV-infected individuals, which will ultimately result in a "graying" of the HIV/AIDS epidemic. In addition, older individuals are engaging in a higher rate of high risk behaviors than had been previously expected. As such, study of older HIV-infected patients, including study of the psychiatric and neurocognitive aspects of the disease, appears highly indicated. Epidemiological studies have demonstrated that HIV infection is associated with higher rates of several psychological/psychiatric disorders when compared to general population base rates. There is also a rich literature that has documented the adverse neurocognitive effects of HIV infection, ranging from subtle cognitive complaints to frank dementia, among younger adults. Although it has been hypothesized that older age may potentiate the deleterious effects of HIV infection, little is actually known, however, regarding the incidence, prevalence, course, and clinical features of HIV-associated psychiatric and cognitive dysfunction among older adults. This article provides an overview of the epidemiology and clinical manifestations of HIV-associated cognitive and psychiatric disorder across the age spectrum, with particular focus on what is known regarding the interaction of advancing age and HIV infection. Future directions for research are suggested, including basic epidemiologic study of incidence and prevalence rates of neurodisease among older HIV-infected adults as well as investigations designed to determine whether the nature, severity, course, or treatment of such disorders differs among older versus younger patients.

Aging and neuro-AIDS conditions and the changing spectrum of HIV-1-associated morbidity and mortality.

Older individuals (>50 years of age) now comprise over 11% of patients with AIDS in the United States. This percentage is expected to continue to grow, due both to the improved longevity of patients prescribed highly active antiretroviral therapy (HAART) and to new infections among older individuals. This review focuses on the neuropsychiatric and neurological conditions that are most likely to be affected by advancing age-HIV-1-associated cognitive-motor disorder, peripheral neuropathy, progressive multifocal leukoencephalopathy, primary CNS lymphoma, and risk for cerebrovascular accident. Age associations with incidence of these disorders and with treatment foci are specified. Implications for future changes in management are discussed.

Computerized and traditional stroop task dysfunction in HIV-1 infection.

Controlled processing, response inhibition, and set adoption were examined in 51 HIV-1 infected participants and 21 uninfected controls who were administered a vocal reaction time (RT) version of the Stroop task (Stroop-RT; J. R. Stroop, 1935) as well as the traditional 100 item paper-and-pencil version. Response set expectancies on the Stroop-RT were manipulated by presenting 50% of trials in homogenous blocks and randomly varying the stimulus type during the remaining trials. As hypothesized, HIV seropositive (HIV+) participants were significantly slower than HIV seronegative controls on both versions of the Stroop. Significant interference effects were apparent on the paper-and-pencil version of the Stroop, but were not as prominent on the Stroop-RT. The HIV+ participants did profit from the blocking manipulation on the Stroop-RT, suggesting that set adoption is retained in HIV infection. These data suggest that HIV infection may result in deficient response inhibition, possibly secondary to frontostriatal dysfunction and dopaminergic alterations.

Visuospatial and Attentional Abilities Predict Driving Simulator Performance Among Older HIV-infected Adults.

OBJECTIVES: To examine the effects of aging and neuropsychological (NP) impairment on driving simulator performance within a human immunodeficiency virus (HIV)-infected cohort. METHODS: Participants included 79 HIV-infected adults (n = 58 > age 50, n = 21 ≤ 40) who completed a NP battery and a personnel computer-based driving simulator task. Outcome variables included total completion time (time) and number of city blocks to complete the task (blocks). RESULTS: Compared to the younger group, the older group was less efficient in their route finding (blocks over optimum: 25.9 [20.1] vs 14.4 [16.9]; P = .02) and took longer to complete the task (time: 1297.6 [577.6] vs 804.4 [458.5] seconds; P = .001). Regression models within the older adult group indicated that visuospatial abilities (blocks: b = -0.40, P <.001; time: b = -0.40, P = .001) and attention (blocks: b = -0.49, P = .001; time: b = -0.42, P = .006) independently predicted simulator performance. The NP-impaired group performed more poorly on both time and blocks, compared to the NP normal group. CONCLUSIONS: Older HIV-infected adults may be at risk of driving-related functional compromise secondary to HIV-associated neurocognitive decline.

Psychological symptomatology in spouses and adult children of alcoholics: an examination of the hypothesized personality characteristics of codependency.

The concept of codependency has been advanced to explain certain psychological traits purported to be characteristic of spouses and adult children of alcoholics. To test the validity of this hypothesized syndrome, 97 female subjects living with either an alcoholic (SA), a psychiatric patient (SP), or dentistry patient (SD) were studied; approximately 50% of subjects had a positive family history (FH+) for alcoholism. All subjects were administered an extensive battery of psychological tests. The results revealed significantly greater levels of psychological symptomatology among the SA and FH+ subjects, in part consistent with the hypothesized symptomatology of codependency.

The indigent alcoholic: personality and psychopathology.

Emotional disorder in a population of indigent detoxified alcoholics from a reception center was assessed by the MMPI and a drinking pattern survey. On the average, these alcoholics had a much greater degree of psychopathology, as measured by various criteria, than found in most other studies. However, a cluster analysis revealed that the population was not homogeneous for psychopathology. The cross-validated clusters yielded three types: I. Severe Emotional Disturbance had extreme elevations on the psychotic and psychopathic deviate scales, and accounted for 28% of the population; II. Impulsive-Antisocial subjects were moderately elevated on psychopathic deviate and depression scales, constituting 26% of population; and III. Little Evidence of Severe Emotional Disturbance had a pattern similar to II but with only one scale somewhat elevated, accounting for 46%. The distinctly different personality patterns of the grouping of indigent alcoholics indicate the need for different treatment strategies.

Neuropsychiatric disturbance is associated with executive dysfunction in HIV-1 infection.

Prominent apathy and/or irritability are frequently observed among individuals infected with the human immunodeficiency virus (HIV). Although these symptoms often occur as part of a mood disorder, compelling evidence suggests that they may occur independently of depression in neurologic disease/disorder. The current study examined the prevalence of both apathy and irritability among a sample of HIV-infected individuals and explored the degree to which these neuropsychiatric (NP) phenomena were associated with performance on neuro-cognitive measures thought to be sensitive to the potential CNS effects of HIV-1. Clinician-administered rating scales assessing apathy and irritability were administered to 65 HIV-seropositive (HIV+) and 21 HIV-seronegative (HIV-) participants who also completed a dual-task reaction time paradigm and the Stroop task. NP disturbance was significantly more prevalent among HIV+ participants compared with HIV- controls and was associated with specific neuro-cognitive deficits suggestive of executive dysfunction. Relative to both HIV- controls and to neuro-psychiatrically intact HIV+ participants, those HIV+ individuals with evidence of prominent apathy and/or irritability showed deficits in dual-task, but not single-task, performance and on the interference condition of the Stroop. Unexpectedly, NP disturbance did not show a robust relationship with HIV disease stage. These results suggest that the presence of prominent apathy and/or irritability among HIV+ individuals may signify greater HIV-associated CNS involvement. In HIV/AIDS, the disruption of frontal-subcortical circuits may be a common mechanism causing both executive dysfunction and NP disturbance.

Dual task performance in HIV-1 infection.

Fifty HIV-infected individuals and 20 uninfected controls participated in an investigation of dual task performance in HIV-1 infection. Participants first engaged in a simple auditory reaction time (RT) task followed by a visual choice RT task (single task condition), and then they simultaneously engaged in both tasks (dual task condition). Under single task conditions, the HIV+ participants did not significantly differ from controls on either simple or choice RT (though a trend was evident on single task choice RT). In contrast, under dual task conditions the HIV+ group's performance decrement, relative to controls, was significantly greater on both simple and choice RT. This dual task decrement was also significantly associated with slower performance on the interference condition of the Stroop. Patients with AIDS tended to have greater dual task decrements than did the pre-AIDS group, though this fell short of statistical significance. These results suggest that HIV-1 infection leads to deficits in divided attention and the simultaneous processing of competing stimuli, deficits which have been linked to disruption of the anterior attentional system.

Concurrent validity of the Neurobehavioral Cognitive Status Exam subtests.

The Neurobehavioral Cognitive Status Exam (NCSE) is a screening measure that assesses numerous neuropsychological (NP) domains. Fifty-four patients completed the NCSE and common NP tests assessing similar abilities. Most subtest screens (brief items that determine whether additional testing should occur) exhibited low false negative rates, but high false positive rates, based upon performance on the follow-up metric items. Each subtest was significantly correlated with the associated NP test. However, using performance on the NP tests as the 'gold standard', the NCSE subtests classified impaired and unimpaired patients at a much lower than expected rate. The latter results draw into question the efficacy of the NCSE subtests in delineating domain-specific cognitive functioning.

Pedophilia and temporal lobe disturbances.

Paraphilias may occur with brain disease, but the nature of this relationship is unclear. The authors report 2 patients with late-life homosexual pedophilia. The first met criteria for frontotemporal dementia; the second had bilateral hippocampal sclerosis. Both were professional men with recent increases in sexual behavior. In both, 18-fluorodeoxyglucose positron emission tomography revealed prominent right temporal lobe hypometabolism. These cases and the literature suggest that bilateral anterior temporal disease affecting right more than left temporal lobe can increase sexual interest. A predisposition to pedophilia may be unmasked by hypersexuality from brain disease. These observations have potential implications for all neurologically based paraphilias.

Apathy, depression, and cognitive performance in HIV-1 infection.

The authors examined the relationship between apathy, depression, and cognitive performance in 48 HIV-1-seropositive and 21 seronegative (control) subjects, using reaction time (RT) and working memory tasks. Apathy, but not depression, was associated with working memory deficits among HIV-seropositive subjects. The cognitive-affective component of the Beck Depression Inventory (BDI), but not apathy, was associated with slowing and decreased accuracy on a choice RT task. The BDI cognitive-affective component was more closely associated than the BDI somatic component with both RT slowing and apathy. Results suggest that prominent symptoms of apathy, independent of depression, may be an important indicator of CNS involvement in HIV infection. Total BDI scores showed a less consistent relationship with neurocognitive performance, suggesting that somatic symptomatology is diagnostically ambiguous among HIV-infected subjects.

Base rate of a WMS-R malingering index in a sample of non-compensation-seeking men infected with HIV-1.

HIV-1 infected persons who are pursuing disability benefits are increasingly seeking neuropsychological assessment for purposes of corroborating functional impairment. Thus, research on the utility of measures of symptom validity among these patients is needed. Recently, Mittenberg, Azrin, Millsaps, and Heilbronner (1993) proposed a malingering index score for the WechslerMemoryScale-Revised that is derived by subtracting the Attention/Concentration Index (ACI) score from the General Memory Index Score (GMI). This study is a cross-validation of the specificity of the GMI-ACI Malingering Index in a sample of 55 non-compensation-seeking HIV-positive (HIV+) patients. An overall false-positive rate of 7% was observed for the GMI-ACI Malingering Index. However, further analyses showed that GMI-ACI Malingering Index scores were correlated with GMI scores such that false-positive errors were substantially higher (18%) among patients who obtained above-average GMI scores. These findings suggest a cautious approach to application of the GMI-ACI Malingering Index, particularly among patients who obtain above-average GMI scores.

Frequencies of MMPI-168 code types among asymptomatic and symptomatic HIV-1 seropositive gay men.

Welsh codes of Minnesota Multiphasic Personality Inventory-168 (MMPI-168) profiles were calculated for 151 HIV-1 seropositive gay men and 27 gay seronegative controls. Although 99% of seropositives' profiles were clinically elevated, the profile configurations among subjects were varied. These data document the presence of considerable emotional distress among HIV-infected individuals, yet the heterogeneity of codes encountered argues against generalizations of seropositive subjects based upon mean MMPI profiles.

Depressed mood and its relationship to neuropsychological test performance in HIV-1 seropositive individuals.

The relationship between depression and neuropsychological test performance in HIV-1 seropositive individuals is unclear. The present study was conducted to determine whether different patterns of neuropsychological test performance would be present in depressed vs. nondepressed individuals infected by the Human Immunodeficiency Virus (HIV-1). It was hypothesized that subjects evidencing depressed mood would demonstrate greater difficulty on measures of neuropsychological function. The subjects were 54 mostly symptomatic HIV-1 seropositive homosexual/bisexual males aged 20 to 60. A neuropsychological test battery together with the Beck Depression Inventory (BDI) was administered to all subjects. Stepwise multiple regression analysis revealed a significant relationship only between scores on the BDI and the Grooved Pegboard test and Trial 6 of the RAVLT. Subjects were then dichotomized using the BDI into high-BDI (M = 28.9) and low-BDI (M = 6.3) groups. Analysis of variance failed to reveal significant group differences between the depressed vs. the non-depressed groups on the neuropsychological measures despite their marked separation on the BDI. Similarly, examination of individual neuropsychological outliers again failed to demonstrate an increased number of outliers in the high- and low-BDI groups. These results suggest that the presence of clinically significant levels of depression in a non-elderly HIV-1 seropositive sample does not necessarily lead to significant neuropsychological dysfunction.