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.

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.

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.

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.

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.

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.

Methylphenidate improves HIV-1-associated cognitive slowing.

Sixteen HIV-1 seropositive individuals participated in a single-blind, placebo-controlled, crossover-design study of the effectiveness of 30 mg/ day of methylphenidate (MPH) in the treatment of HIV-associated cognitive slowing. Regression analyses revealed that participants who entered the study with a greater degree of either depressive symptomatology or cognitive slowing tended to demonstrate a better response to MPH on computerized measures of choice and dual-task reaction time. Participants without evidence of cognitive slowing at study entry did not show greater improvement on MPH than on placebo. Contrary to expectation, symptoms of depression did not respond better to MPH than to placebo, regardless of initial symptomatology. Information processing slowing in HIV-1 infection therefore appears amenable to pharmacologic intervention with the dopamine agonist MPH. However, results suggest clinicians should consider reserving the use of MPH for patients with more pronounced cognitive and affective deficits.

Long-term effects of high-dose zidovudine treatment on neuropsychological performance in mildly symptomatic HIV-positive patients: results of a randomized, double-blind, placebo-controlled investigation.

This study examined the treatment outcome of high-dose (1500 mg/day) zidovudine (AZT) on neuropsychological (NP) functioning (Trailmaking Test A & B, WAIS-R Digit Symbol, and Rey Auditory Verbal Learning Test) across a 12-month period in mildly symptomatic HIV-1 seropositive men (n = 46 at entry) enrolled in a randomized, double-blind, placebo-controlled trial (VA Cooperative Studies Program #298). Neither short-term (0-6 months) nor long-term (0-12 months) AZT administration revealed enhancement in NP performance. The results suggest that, although AZT may afford patients prophylactic benefits, protracted high-dose AZT treatment does not improve NP functioning in mildly symptomatic HIV-positive individuals.

Screening for drug and alcohol abuse among older adults using a modified version of the CAGE.

This study examined the sensitivity, specificity, and receiver operating characteristics (ROC) curves of a modified version of the CAGE, a screening measure used in the detection of older alcohol- and drug-abusing individuals. In a retrospective review of clinical records of 976 patients screened by a geriatric substance abuse program, the authors examined patients' responses on a modified version of the CAGE that included queries regarding drug use. The CAGE was administered to individuals age 50 or over draw from three diagnostic groups: alcohol abuse/dependence, drug abuse/dependence, and normal controls. Analysis of variance and discriminant function analyses revealed that the modified CAGE was able to discriminate both alcohol and drug abusers from controls. Analyses examining test sensitivity, specificity, and ROC curves revealed the CAGE to demonstrate excellent sensitivity but poor specificity. Omitting the "cut down'' item from the CAGE significantly improved specificity with only a modest drop in sensitivity. Given the ease of administration and sensitivity to both alcohol and drug abuse, these data suggest that the modified CAGE is well suited as a screening instrument for geriatric drug and alcohol abuse.

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.

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.

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.

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.

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.

Executive dysfunction in Alzheimer's disease: association with neuropsychiatric symptoms and functional impairment.

Relationships between measures of executive skills and neuropsychiatric and functional status were examined in a group of 31 patients with Alzheimer's disease. Deficits in four executive skills tests were significantly associated with the Agitation/Disinhibition factor score and Total Neuropsychiatric score on the Neurobehavioral Rating Scale, as well as the Activities subscore on the Blessed Dementia Scale. The majority of these associations remained significant after covariance for Mini-Mental State Examination scores. Executive dysfunction is associated with clinically relevant neuropsychiatric symptoms and functional impairment in Alzheimer's disease. These associations may be independent of other cognitive deficits such as memory, language, and visuospatial skills, and may not be appreciated on routine clinical evaluations. Executive skills deficits, neuropsychiatric symptoms, and functional disability may emerge from shared neurobiological mechanisms.

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.

Depression predicts procedural but not episodic memory in HIV-1 infection.

Forty-three homosexual/bisexual males with HIV-1 infection participated in a study that sought to determine: (1) whether increased levels of self-reported depressive symptomatology were associated with poorer performance on episodic or procedural memory tasks, (2) the relative strength of association between the affective/cognitive or somatic symptoms of depression and memory deficits and level of immunosuppression, and (3) whether increased depression or neuropsychological deficits are associated with degree of immunosuppression. Linear regression analyses revealed that increased affective/cognitive symptomatology was correlated with poorer performance on a procedural memory task, but was not correlated with performance on an episodic memory task or degree of immunosuppression. In contrast, somatic symptoms showed the strongest association with level of immunosuppression, but were not correlated with performance on the memory tasks. These findings underscore the complex interplay between neuropsychiatric and neuropsychological symptomatology in HIV-1 infection.

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.

Subjective complaints versus actual cognitive deficits in predominantly symptomatic HIV-1 seropositive individuals.

The relationship of self-reported cognitive, motor, and affective complaints to actual neuropsychological functioning was explored in a cohort of predominantly symptomatic HIV-1 seropositive individuals. Ninety-two symptomatic HIV-1 infected subjects were questioned about complaints common in HIV infection and were assessed with a comprehensive neuropsychological test battery. No relationship was found between subjective complaints and cognitive functioning, yet a significant relationship was found between self-reported difficulties and formal measures of affect and mood. Failure to show a relationship between self-reported cognitive status and actual neuropsychological functioning in this cohort suggests that complaints of cognitive decline may be attributable to emotional factors.