Influence of depression and HIV serostatus on the neuropsychological performance of injecting drug users

Depression is common in injecting drug users (IDUs), a group at significant risk for HIV infection. Moreover, both HIV infection and depression have been shown to adversely effect neurocognitive abilities. Understanding the effects of depression and HIV infection on the neurocognitive functioning of drug users is essential for appropriate management and/or treatment of these deficits in this population. Therefore, the purpose of the present study was to investigate the effects of depression and HIV status on cognitive functioning in 100 male and female IDUs. Participants were categorized into three groups of depression severity based on their scores on the Beck Depression Inventory: no depression, mild depression, and moderate to severe depression. The effects of depression and HIV serostatus as well as their interaction were assessed. Results indicated that regardless of serostatus, those with moderate to severe depression had lower scores on cognitive measures. These findings suggest that although depression contributes to poor neuropsychological performance in IDUs, this effect was not exacerbated by HIV infection. The finding also illustrates the importance of addressing depression-related neurocognitive deficits in IDUs.     

Metacognition in HIV-1 seropositive asymptomatic individuals: self-ratings versus objective neuropsychological performance. Multicenter AIDS Cohort Study (MACS)

This study examined the relationship between actual and self-reported neuropsychological deficits, depression, and HIV-1 serostatus. The subjects, who consisted of 479 individuals, 256 who were HIV seronegative (SN) and 233 who were HIV-1 seropositive though still asymptomatic (ASP), were administered a standardized neuropsychological screening battery consisting of measures of attention, motor speed, psychomotor speed, verbal memory, verbal fluency, and depression. To assess subjects' subjective sense of their cognitive status, the Cognitive Failures Questionnaire (CFQ), a 25-item self-report questionnaire, was also administered. The results of MANOVA failed to reveal group differences between the SN and ASP groups on the measures of neuropsychological function. Similarly, the ASP and SN groups did not differ on the number or severity of reported cognitive failures. However, a positive correlation was found between CFQ scores and level of depression. These results do not support the hypothesis that ASP individuals are aware of cognitive decline prior to detection using standard neuropsychologic screening instruments. The data do suggest that the presence of depressed mood, independent of serostatus or actual neuropsychological impairment, is associated with increased cognitive complaints.     

Asymptomatic HIV infection does not cause EEG abnormalities: results from the Multicenter AIDS Cohort Study (MACS)

We conducted EEG testing in 200 asymptomatic homosexual men, half of whom were HIV seropositive. We chose to include half of the subjects because they were rated as impaired on a neuropsychological screening test. We used both traditional visual EEG interpretation and quantitative EEG analysis. Abnormal EEGs and borderline degrees of EEG slowing occurred in 32% of these men. These EEG changes were not related to HIV serostatus. EEG changes did correlate with the impaired neuropsychological test performance. Clinicians faced with abnormal EEG results or borderline EEG slowing in an asymptomatic HIV-seropositive patient should not attribute the EEG change to effects of the serostatus itself but should look for other causes.     

Neuropsychiatric aspects of HIV-1 infection in gay men: Controlled investigation of psychiatric, neuropsychological and neurological status

The aim of this study was to determine whether HIV infection is associated with psychiatric morbidity or neuropsychological impairment in asymptomatic and early symptomatic stages of disease in gay men. The subjects were 100 gay men (68 HIV − ve, 32 HIV + ve, 6 being CDC IV). All subjects were recruited at the time of requesting their first HIV test and the assessment was double-blind to HIV serostatus. There were no differences in psychiatric status or neuropsychological performance between the HIV − ve and HIV + ve groups. Multiple regression analysis and logistic regression were used to identify factors associated with psychiatric morbidity, neuropsychological impairment and subjective reporting of memory problems and physical symptoms for all 100 subjects.

Previous psychiatric history and current illegal (non-dependent) drug use were associated with psychiatric morbidity, poor education was assciated with neuropsychological impairment and psychiatric status (score on HAD and PSE) was associated with subjective reporting of memory problems and physical symptoms.     

Family history of dementia predicts worse neuropsychological functioning among HIV-infected persons

HIV-negative individuals with a family history of dementia (FHD) are more likely to develop dementia than those without FHD. Whether FHD increases risk for neuropsychological (NP) impairment in HIV+ persons is unknown. As part of a multisite study into HIV-associated neurocognitive disorders (HAND), the authors captured FHD with a free-response, self-report question, and assessed NP performance with a comprehensive battery of tests. The authors examined HIV+ persons with (N=190) and without (N=916) self-reported FHD. Despite the fact that the FHD group had factors typically associated with better NP performance (e.g., higher CD4 counts and estimated verbal IQ), persons with FHD had significantly worse NP ability than those without FHD as measured by a Global Deficit Score. Thus, FHD appears to be a risk factor for HAND; the mechanism(s) underlying how FHD contributes to NP impairment among HIV+ persons warrants study.     

Reliable screening for neuropsychological impairment in multiple sclerosis

In an earlier study, we developed the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) to assist in the screening for neuropsychological (NP) impairments. Self-report MSNQ scores correlated significantly with measures of depression, whereas informant-report MSNQ scores correlated with cognitive performance, but not depression. This study was criticized for use of a small sample and lack of data regarding normal performance and test-retest reliability. The present study was designed to replicate the earlier work with a larger sample of patients and normal controls obtained from multiple sites. We also evaluated the test-retest reliability and predictive validity of the MSNQ. The sample included 85 multiple sclerosis (MS) patients and 40 normal controls, matched on demographic variables. All participants completed the MSNQ and underwent NP testing. Thirty-four patients were re-examined at one week. Pearson and ANOVA techniques were utilized for univariate comparisons. Bayesian statistics were calculated to assess predictive validity. Patient self- and informant-report MSNQ scores differed from normal and test retest reliability indices were high. Both self- and informant-reports were correlated with cognitive dysfunction and depression scales. Self-report MSNQ scores correlated more strongly with depression than cognitive performance, whereas the opposite pattern was observed with informant-report scores. Bayesian statistics showed that informant-report MSNQ scores predict cognitive impairment and patient self-report scores identify patients with cognitive impairment or depression. It is concluded that the MSNQ is useful, although patient self-reports may be exaggerated in depressed patients or reduced in patients with severe cognitive impairment.     

The relationship between age and cognitive function in HIV-infected men

Several studies have identified increased age as a risk factor for the development of cognitive impairment in human immunodeficiency virus (HIV)-infected subjects, but few have examined the potential synergistic effect of age and HIV serostatus on cognitive decline. The authors examined the possible combined effect of age and HIV serostatus on cognitive decline in 254 subjects stratified by age group and HIV status. After controlling for the effect of education, there were significant effects for serostatus and age group on overall cognitive impairment and a number of neuropsychological measures but no interaction effects. These data suggest that older seropositive individuals are not at an increased risk for HIV-related cognitive impairment when normal age-related cognitive changes are considered.     

The relationship among depression, subjective cognitive impairment, and neuropsychological performance in multiple sclerosis

The aim of this study was to examine, within the context of a treatment study, the relative contributions of depression and neuropsychological performance on patient ratings of cognitive functioning in a cohort of 58 moderately-depressed multiple sclerosis (MS) patients. All participants were randomized to one of three 16-week conventional treatments for depression. Assessments were conducted pre- and post-treatment using: (1) Cognitive Function subscale of the Multiple Sclerosis Quality of Life-54 (MSQOL-54) to evaluate subjective cognitive impairment (SC), (2) Beck Depression Inventory (BDI), and (3) a neuropsychological index score (NP). Prior to treatment, 8% of the variance in SC was explained by NP, whereas 14% of the variance was explained by BDI, above and beyond NP. At post-treatment, patients were classified as 'responders' (BDI < 11) and 'non-responders' (BDI > or = 11). Among those participants classified as 'responders', NP accounted for 39% of the variance in SC, and BDI did not significantly predict SC. The results of this study suggest that depression may influence subjective reports of cognitive impairment, but these reports may not be reliably related to objective neuropsychological performance. Furthermore, patients may be more accurate reporters of their cognitive impairment after successful treatment for depression, suggesting that depression decreases the accuracy of patient reported cognitive impairment.     

The impact of neuropsychological functioning and depressed mood on functional complaints in HIV-1 infection and methamphetamine dependence

Diagnosis of neurobehavioral syndromes associated with HIV infection requires the determination that neuropsychological (NP) deficits are present, are not caused by any comorbid (e.g., psychiatric) condition, and significantly affect everyday functioning. Methamphetamine (Meth) dependence and depression are common comorbid conditions with HIV and may complicate diagnosis of HIV-associated neurobehavioral syndromes. The current study examined the complex relationships between depression and NP impairment, and self-report of problems with everyday functioning, in 362 adults with HIV infection or Meth dependence, or both. Everyday functioning was measured with questionnaires of instrumental activities of daily living (IADLs) and reported cognitive difficulties. Results indicate that comorbid HIV and Meth did not increase the likelihood of complaints regarding everyday functioning, beyond what was seen with either single risk factor. Across all groups, depressive symptoms predicted greater IADL decline and cognitive complaints, while NP impairment predicted cognitive complaints more than IADL decline. Both IADL decline and cognitive complaints were associated with higher rates of unemployment and worse clinician ratings of overall functioning (Karnofsky ratings), even when depressive symptoms were controlled. These results suggest that depressive symptoms should not be used to dismiss subjective complaints related to everyday functioning even though depressive symptoms account for significant variance in self-reported complaints. Additional research is needed to clarify the potentially reciprocal causal relationships between depressive symptoms and impairment in everyday functioning.     

Relationship between alcohol use/abuse, HIV infection and neuropsychological performance in African American men

This study examines the impact of alcohol use and HIV infection on neuropsychological performance in a sample of 497 community-resident African American men. HIV serostatus and alcohol use (during the past 12 months) exerted an interactive effect on psychomotor speed, reaction time, and motor speed, and in general, HIV infected heavy drinkers evidenced significantly poorer performance than other HIV positive subjects. Main effects for HIV serostatus were noted for reaction time, with seronegative men performing better than seropositives. This study examines a sample of men who continue to show increases in HIV infection, however, sample specific issues such as comorbid substance use, past histories of head injury, and lack of data on alcohol abuse and dependence require caution in definitively attributing the findings solely to alcohol and HIV. However, these findings suggest that relatively recent heavy alcohol use may represent a potential risk factor for more rapid or pronounced cognitive decline in HIV positive individuals, and that these patterns may be even more pronounced in persons with comorbid substance use.     

Initial validation of a screening battery for the detection of HIV-associated cognitive impairment

This study sought to develop and validate a screening battery for detecting HIV-related neuropsychological (NP) impairment. Six NP measures representing the ability areas most likely affected by HIV infection were paired in 14 combinations and their diagnostic accuracy rates compared. The measures were selected from a larger NP battery administered to 190 HIV-seropositive (HIV+) participants. Screening battery performance was classified as NP impaired if demographically corrected T-scores fell below 40 on both tests, or below 35 on one test. Using blind clinical ratings of NP test results from the larger battery as the "gold standard" for global NP status (impaired or unimpaired), we found that several test combinations demonstrated adequate diagnostic accuracy in detecting NP impairment. The most sensitive test combinations were the Hopkins Verbal Learning Test-Revised (HVLT-R; Total Recall) and the Grooved Pegboard Test nondominant hand (PND) pair and the HVLT-R and WAIS-III Digit Symbol (DS) subtest pair (sensitivity = 78% and 75%, respectively). Both test combinations (HVLT-R/PND, HVLT-R/DS) were more accurate than the HIV Dementia Scale (HDS) in classifying HIV+ participants as NP impaired or unimpaired. Results suggest that demographically corrected T-scores from pairs of common NP measures may serve as valid screening instruments to identify subjects with HIV-related neurocognitive impairment who could benefit from more extensive NP examination.     

Heavy alcohol consumption in individuals with HIV infection: effects on neuropsychological performance.

Higher rates of alcohol use have been reported in HIV+ individuals compared to the general population. Both heavy alcohol use and HIV infection are associated with increased risk of neuropsychological (NP) impairment. We examined effects of heavy active alcohol use and HIV on NP functioning in a large sample of community-residing HIV+ individuals and HIV- controls. The four main study groups included 72 HIV- light/non-drinkers, 70 HIV- heavy drinkers (>100 drinks per month), 70 HIV+ light/non-drinkers, and 56 HIV+ heavy drinkers. The heavy drinking group was further subdivided to assess effects of the heaviest levels of active alcohol use (>6 drinks per day) on NP functioning. A comprehensive NP battery was administered. Multivariate analysis of covariance was employed to examine the effect of HIV and alcohol on NP functioning after adjusting for group differences in age and estimated premorbid verbal intellectual functioning. The analyses identified main effects of heavy drinking and HIV on NP function, with greatest effects involving the contrast of HIV+ heavy drinkers and the HIV- light drinkers. Synergistic effects of heaviest current drinking and HIV infection were identified in analyses of motor and visuomotor speed. Supplementary analyses also revealed better NP function in the HIV+ group with antiretroviral treatment (ART) and lower level of viral burden, a finding that was consistent across levels of alcohol consumption. Finally, heavy alcohol use and executive functioning difficulties were associated with lower levels of self-reported medication adherence in the HIV+ group. The findings suggest that active heavy alcohol use and HIV infection have additive adverse effects on NP function, that they may show synergistic effects in circumstances of very heavy active alcohol use, and that heavy drinking and executive functioning may mediate health-related behaviors in HIV disease.     

HIV-1 infection and intravenous drug use: longitudinal neuropsychological evaluation of asymptomatic subjects.

A previous baseline cross-sectional comparison of cognitive performance of a group of AIDS-free, HIV-seropositive intravenous drug users with seronegative control intravenous drug users revealed no significant differences attributable to HIV. We now present longitudinal follow-up results from the same cohort of 160 intravenous drug users. There were no differences in performance by serostatus group at either 6- or 12-month follow-up visits, although differences by age and education were observed. Improvement in performance secondary to practice effects was comparable in both serostatus groups. These findings confirm that chronic intravenous drug use may be associated with a wide range of neuropsychological deficits, but there is no evidence that such preexisting deficits interact with HIV infection to produce additional cognitive impairment in otherwise asymptomatic intravenous drug users. Together with results from other high-risk groups such as homosexual/bisexual men and hemophiliacs, these results confirm that neurocognitive abnormalities during the presymptomatic stages of HIV infection are rare, regardless of the route of acquisition of the virus.     

Neuropsychological functioning in a cohort of HIV infected women: importance of antiretroviral therapy.

We evaluated neurocognitive function in 149 HIV-seropositive and 82 seronegative women enrolled in the Women's Interagency HIV Study (WIHS), a large multi-center study of disease progression in women living with HIV/AIDS. We evaluated the prevalence of abnormal neuropsychological (NP) test findings in HIV-seropositive and seronegative women and factors associated with increased risk of abnormal NP test performance. Risk of NP impairment was no higher for HIV positive women receiving antiretroviral therapy at testing than for HIV-negative women (OR = 1.00). However, the risk of abnormal NP performance increased significantly for seropositive women not receiving antiretroviral therapy (OR = 2.43). Further, treatment status was a significant predictor of NP impairment in a multivariate analysis that included viral load (OR = 1.48) and CD4 count (OR = 1.08) which were not significant. The multivariate analyses controlled for substance use, age, education, head injury, ethnicity, estimated IQ, and psychological distress. This study emphasizes the critical association of antiretroviral therapy with the risk of neurocognitive impairment in women living with HIV/AIDS.     

Translational spatial task and its relationship to HIV-associated neurocognitive disorders and apolipoprotein E in HIV-seropositive women

HIV-associated neurocognitive disorders (HAND) continue to be a neurological complication of HIV infection in the era of combined antiretroviral therapy. Hippocampal neurodegeneration and dysfunction occurs as a result of HIV infection, but few studies to date have assesses spatial learning and memory function in patients with HAND. We used the Memory Island (MI) test to study the effects of HIV infection, apolipoprotein E (ApoE) allele status, and cerebral spinal fluid (CSF) ApoE protein levels on spatial learning and memory in our cohort of Hispanic women. The MI test is a virtual reality-based computer program that tests spatial learning and memory and was designed to resemble the Morris Water Maze test of hippocampal function widely used in rodent studies. In the current study, HIV-seropositive women (n?=?20) and controls (n?=?16) were evaluated with neuropsychological (NP) tests, the MI test, ApoE, and CSF ApoE assays. On the MI, the HIV-seropositive group showed significant reduced learning and delayed memory performance compared with HIV-seronegative controls. When stratified by cognitive performance on NP tests, the HIV-seropositive, cognitively impaired group performed worse than HIV-seronegative controls in ability to learn and in the delayed memory trial. Interestingly, differences were observed in the results obtained by the NP tests and the MI test for ??4 carriers and noncarriers: NP tests showed effects of the ??4 allele in HIV-seronegative women but not HIV-seropositive ones, whereas the converse was true for the MI test. Our findings suggest that the MI test is sensitive in detecting spatial deficits in HIV-seropositive women and that these deficits may arise relatively early in the course of HAND.     

Cognitive functioning during highly active antiretroviral therapy interruption in human immunodeficiency virus type 1 infection

Although no longer considered therapeutically beneficial, antiretroviral treatment interruptions (TIs) still occur frequently among patients with human immunodeficiency virus (HIV) infection for a variety of reasons. TIs typically result in viral rebound and worsening immunosuppression, which in turn are risk factors for neurocognitive decline and dementia. We sought to determine the extent of neurocognitive risk with TIs and subsequent reintroduction of highly active antiretroviral therapy (HAART) by using a comprehensive, sensitive neuropsychological assessment and by concurrently determining changes in plasma and cerebrospinal fluid (CSF) viral load and CD4 counts. Prospective, serial, clinical evaluations including neuropsychological (NP) testing and measurement of plasma HIV RNA and CD4 count and mood state were performed on HIV-1—infected individuals (N=11) at three time points: (1) prior to a TI, while on HAART; (2) after TIs averaging 6 months; and (3) after reinitiating HAART therapy. During TI, plasma HIV RNA increased and CD4 counts declined significantly, but NP performance did not change. Following reinitiation of HAART, viral loads fell below pre-TI levels, and CD4 counts rose. Improved viral suppression and immune restoration with reinitiation of HAART resulted in significant improvement in neurocognitive performance. No changes on comprehensive questionnaires of mood state were observed in relation to TI. NP performance and mood state remained stable during TIs despite worsened viral loads and CD4 counts. Because “practice effects” are generally greatest between the first and second NP testing sessions, improvement at the third, post-TI time point was unlikely to be accounted for by practice. TIs of up to 6 months appear to be neurocognitively and psychiatrically safe for most patients.     

Incident major depression does not affect neuropsychological functioning in HIV-infected men.

The diagnosis of lifetime major depressive disorders (MDDs) and of current major depressive episodes (MDEs) are relatively common in HIV-infected individuals, and often are assumed to influence neuropsychological (NP) performance. Although cross-sectional studies of HIV-infected individuals generally have found no systematic link between current MDE or depressive symptoms and NP performance, longitudinal studies are needed to clarify whether incident MDE may impact NP functioning in at least some cases. Two hundred twenty-seven human immunodeficiency virus (HIV)-infected adult men, who did not meet criteria for a current MDE at baseline, participated in a longitudinal NP study for an average of two years. Participants received repeated NP assessments, as well as structured psychiatric interviews to ascertain presence or absence of both lifetime MDD and current MDE. Ninety-eight participants had a lifetime history of MDD, and 23 participants met criteria for incident MDE at one of their follow-up evaluations. Groups with and without lifetime MDD and/or incident MDE had comparable demographics, HIV disease status and treatment histories at baseline, and numbers of intervening assessments between baseline and the final follow-up. Lifetime MDD was associated with greater complaints of cognitive difficulties in everyday life, and such complaints were increased at the times of incident MDE. However, detailed group comparisons revealed no NP performance differences in association with either lifetime or incident major depression. Finally, NP data from consistently nondepressed participants were used to develop "norms for change" and these findings failed to show any increased rates of NP worsening among individuals with incident MDE. Our results suggest that neurocognitive impairment and major depression should be considered as two independent processes.     

Fatigue in HIV/AIDS is associated with depression and subjective neurocognitive complaints but not neuropsychological functioning

Fatigue and depressive symptoms are common in HIV-infection. The relationship between these symptoms and neuropsychological functioning is poorly understood, particularly in symptomatic infection/AIDS. This study examined the associations among fatigue, depressive symptoms, subjective neurocognitive complaints, and objective neuropsychological performance in HIV/AIDS. Sixty-eight men with HIV-infection (27 adults with HIV-infection but not AIDS and 41 with AIDS diagnosis) completed a neuropsychological test battery and self-report measures of fatigue (Fatigue Severity Scale), depressive symptoms (Beck Depression Inventory), and subjective neurocognitive complaints (Patient's Assessment of Own Functioning). High levels of fatigue were endorsed by participants. Fatigue severity was related to depressive symptoms but not to AIDS diagnosis or medication status. Verbal learning and motor function was worse in participants with AIDS, but neuropsychological functioning was not significantly correlated with fatigue or depressive symptoms. Subjective neurocognitive complaints were predicted by both depressive symptoms and fatigue. Our results suggest that adults with fatigue and HIV-infection (with or without AIDS) should be screened for depression. Neither fatigue nor depressive symptoms appear to affect neuropsychological functioning in HIV/AIDS. Future research is needed to develop and evaluate instruments and methods to differentiate depression-related fatigue from fatigue that may reflect underlying medical disease. Such research will further the development of effective treatments for fatigue associated with HIV-infection.