Measurement of depression and neuropsychological impairment in HIV-1 infection.

Depression and neuropsychological (NP) impairment were examined in 30 HIV-1 seropositive symptomatic, 15 seropositive asymptomatic, and 14 seronegative control participants. Items on the Beck Depression Inventory (BDI) were separated into somatic and affective components to examine effects of illness on depression. Twenty-two NP tests tapped motor and psychomotor function, cognitive flexibility, and memory. The symptomatic seropositive group had the highest mean depression scores. However, these group differences were seen with the somatic component, not the affective. No significant correlations were obtained between NP tests and the affective component. Although 3 of 11 psychomotor measures were modestly correlated with the BDI total and somatic component, depression was generally unrelated to NP performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuropsychological performance and CD4 levels in HIV-1 asymptomatic infection

The performance of 68 HIV-1 seropositive asymptomatic (HIV+) subjects stratified on CD4 levels were compared with 82 HIV-1 seronegative (HIV-) subjects on a battery of neuropsychological, mood state, and perceived health status measures. The neuropsychological test battery included measures of attention, reaction time, memory, intellectual ability, psychomotor speed, frontal lobe or "executive" function, and decision time. None of the HIV+ subjects were taking antiviral agents. The groups did not differ for age, mood state, or WAIS-R Verbal and Performance IQ scores. Due to group differences for education and weekly ethanol consumption, both variables were used as covariates in multivariate analyses of variance. Relatively few differences were observed between subgroups of HIV+ patients or between these subgroups and control subjects. These data suggest that factors other than absolute levels of immunosuppression as expressed by CD4 levels alone, appear to be responsible for the deficits observed in HIV+ asymptomatic patients.     

Neuropsychiatric HIV-1 infection study: in Kenya and Zaire cross-sectional phase I and II

The objective of the study was to determine the prevalence and natural history of human immunodeficiency virus type 1 (HIV-1) associated psychiatric, neuropsychological and neurological abnormalities. A total of 408 subjects were recruited in Nairobi and Kinshasa. The study consisted of a cross sectional phase and a longitudinal follow up. Assessment was made by a data collection instrument including six modules. The intercentre and intracentre reliability in the use of the each module have been formally evaluated. The mean global score on the Montgomery-Asberg Depression Rating Scale was significantly higher in symptomatic seropositive individuals than in matched seronegative controls. In conclusion, these data suggest that the risk of subtle cognitive deficits may be increased in asymptomatic stages of HIV-1 infection.     

Triphenyltin acetate toxicity: a biochemical and ultrastructural study on mouse thymocytes

Eighty-five subjects at various stages of human immunodeficiency virus (HIV-1) infection and 39 seronegative controls underwent neurological and neuropsychological evaluation to assess the relationship between cognitive test results and subjective complaints (cognitive, affective, motor, and other). The effect of psychiatric disorders on the association between cognitive performance and complaints of the patients was also examined. Patients with symptomatic infection had higher frequency of complaints than subjects at asymptomatic stage. Detailed neuropsychological examination confirmed a strong association between poor verbal memory and cognitive complaints. Poor performance on cognitive speed and flexibility was associated with motor complaints and motor abnormalities. These associations were not explained by psychiatric disorders or elevated depression questionnaire scores. Our observations indicate that, especially in symptomatic HIV-1 infection cognitive changes reported by patients often reflect "objective" cognitive decline, and may be the earliest signs of HIV-1 associated cognitive disorder. No direct relationship was observed between "subjective" complaints and neuropsychological performance of asymptomatic subjects. Understanding the significance of reported cognitive changes have important therapeutic implications.     

Cognitive function in asymptomatic HIV-1 infection: The effects of age, education, ethnicity, and depression.

Examined whether individuals with asymptomatic HIV-1 infection exhibit subtle cognitive deficits relative to healthy seronegative control Ss. 122 symptomatic seropositive homosexual and bisexual White men were compared with 59 seronegative homosexual or bisexual men (all Ss aged 20–71 yrs) on a battery of neuropsychological tests. Age, education, ethnicity, and depression were controlled as potential confounding variables. Seropositive Ss performed below seronegative controls on measures of verbal fluency, recall of logical discourse material (younger seropositive Ss only), and arithmetic. No group differences were found on visuospatial measures, abstract reasoning, attention, or set shifting. Ethnicity (Hispanic vs non-Hispanic) and education effects were observed only on select language measures. Depression did not adversely affect performance scores. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The relationship between working memory capacity and executive functioning: Evidence for a common executive attention construct.

Attentional control has been conceptualized as executive functioning by neuropsychologists and as working memory capacity by experimental psychologists. We examined the relationship between these constructs using a factor analytic approach in an adult life span sample. Several tests of working memory capacity and executive function were administered to more than 200 subjects between 18 and 90 years of age, along with tests of processing speed and episodic memory. The correlation between working memory capacity and executive functioning constructs was very strong (r = .97), but correlations between these constructs and processing speed were considerably weaker (rs ≈ .79). Controlling for working memory capacity and executive function eliminated age effects on episodic memory, and working memory capacity and executive function accounted for variance in episodic memory beyond that accounted for by processing speed. We conclude that tests of working memory capacity and executive function share a common underlying executive attention component that is strongly predictive of higher level cognition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Immune function and neuropsychological performance in HIV-1-infected homosexual men

This study explores the relationship of immune dysfunction to the neuropsychological performance of individuals infected with HIV-1. Fifty-five HIV-positive homosexual men and 37 negative homosexual controls were evaluated using neuropsychological measures, physical exams, and measures of immune functioning. There were no significant differences favoring HIV-negative subjects over HIV-positive subjects. HIV-positive subjects, in fact, performed slightly better on attention and memory procedures. The HIV-positive subjects were then stratified according to the Centers for Disease Control symptom groupings (Group II, asymptomatic, n = 19; Group III, lymphadenopathy, n = 17; and Group IVA or C-2, symptomatic, non-AIDS, (n = 19). There were no significant neuropsychological differences among the three CDC groups. The HIV-positive subjects were also stratified on two measures of immune functioning: absolute CD4 counts (< 200, 201-400, > 400) and beta 2-microglobulin (beta 2M) (> or = 5.0, 3.0-5.0, < 3.0). Individuals with greater immune compromise, as measured by beta 2M, were more impaired on measures of attention and memory and had greater overall neuropsychological impairment (p < 0.05). Furthermore, 57% of the subjects who were abnormal on beta 2M were also impaired on measures of attention and memory, whereas only 14% of those with normal beta 2M were impaired on these same measures (p < 0.05). These results suggest that HIV-positive asymptomatics without evidence of immune compromise do not appear to be at greater risk of cognitive impairment than HIV-negative controls. However, for those HIV-positive individuals who are immune-compromised (even while asymptomatic), there is increased risk of neuropsychological impairment. These results also suggest that knowledge of serostatus and the use of the CDC classification system alone are insufficient in exploring the development of neuropsychiatric changes in HIV-1 infection.     

Effect of minor head injury on neuropsychological performance in asymptomatic HIV–2 infection.

The performance of 24 asymptomatic Ss who were seropositive for HIV–2 and who had a history of minor closed head injury (CHI) was compared with the performance of age- and education-matched HIV–2+ and HIV–2– controls on a battery of neuropsychological tasks. Ss were volunteers for a longitudinal study of HIV–2 infection and were not selected because of neurobehavioral symptoms. No differences were found for measures of intellectual ability, frontal and executive function, memory, attention and concentration, psychomotor speed, auditory reaction time (RT), or the Hamilton depression and anxiety rating scales. Differences were observed between the 2 HIV–2+ groups on a visual RT measure, but these effects failed to reach significance after Bonferroni's correction. The failure to find group differences may be due to the short duration of unconsciousness experienced by the CHI group. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Diversification of subtype E human immunodeficiency virus type 1 env in heterosexual seroconverters from Northern Thailand

The C2-V3 region of the human immunodeficiency virus (HIV)-1 env was determined from 15 northern Thailand seroconverters between 1993 and 1995. Similar sequences were also determined from 18 seroconverting injection drug users in Baltimore. All seroconverters from northern Thailand were infected with subtype E HIV-1 on the basis of env sequences. Intersubject viral DNA distances increased from 2.3% in asymptomatic HIV-1-infected subjects characterized between 1990 and 1992 to 7.8% in these more recent seroconverters from Thailand. On the other hand, sequences from 18 seroconverters from Baltimore had a mean intersubject distance of 13.2%. The genetic diversity within HIV-1 subtype E in seroconverters in Thailand has increased significantly but is still less than that observed in HIV-1 from seroconverters in the United States, where the epidemic of HIV-1 infection is more mature. These results suggest that continued monitoring of the molecular epidemiology of HIV-1 infection in Thailand will be important for HIV vaccine development and evaluation.     

Visual attention in HIV-1 infection.

27 nondemented HIV-seropositive men and 13 seronegative controls performed 2 versions of a spatial attention task that engaged either automatic or controlled attentional processing. Ss also performed a 3rd task requiring divided attention, which tested for potential deficits in attentional resources. HIV-seropositive symptomatic Ss were impaired on the automatic processing task, whereas asymptomatic Ss performed the task normally compared with controls. In contrast, no differences were observed among the 3 groups on the controlled attention task. However, both seropositive groups showed deficits on the divided attention task. These results suggest that deficits in selective attention are present early in the course of HIV-1 infection. The most prominent impairment is seen on tasks that are highly demanding of attentional resources, whereas deficits in automatic processing develop later in the disease process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuropsychological correlates of short-term memory distractor tasks among patients with surgical repair of anterior communicating artery aneurysms.

The relative utility of the visual consonant trigram (VCT) and release from proactive inhibition (PI) versions of the short-term memory (STM) distractor task in investigating the separate but related cognitive realms of memory and executive frontal lobe functioning were explored in patients with anterior communicating artery (ACoA) aneurysms n?=?24. Compared with normal controls n?=?19, ACoA patients were impaired on clinical measures of memory and on measures of executive functioning, including concept formation and fluent word generation. Furthermore, ACoA patients were impaired on the VCT task but not on the release-from PI task, indicating a differential sensitivity of these tasks to the impairment manifested by ACoA patients. Regression modeling indicated that the VCT and release-from-PI tasks were closely associated with clinical memory tests, although the release-from-PI-task was also associated with fluency, an executive functioning domain. In general, our results fail to support the broad generalization that impaired performance on STM distractor tasks is necessarily symptomatic of frontal lobe dysfunction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Executive function deficits in mild Alzheimer's disease.

Twenty mildly impaired patients with Alzheimer's disease (AD; Mini-Mental State Examination; [MMSE]?=?25.1) and 20 controls (MMSE?=?29.4) were administered 7 tests to assess executive function. Tests of memory, naming, and copying were included. The executive function tests were the Self-Ordering Test, Controlled Oral Word Association Test (FAS), Trail Making Test, Hukok Logical Matrices, the Proverb Interpretation Test, the Similarities subtest of the Wechsler Adult Intelligence Scale—Revised, and the Cued Reaction Time Test. AD patients differed significantly from controls on 4 executive function tests (the Self-Ordering, Hukok, Trail Making, and FAS) and on the memory test. The executive function tasks on which the AD patients were impaired in comparison with controls primarily required concurrent manipulation of information. Tests of simple concept formation, cue-directed behavior, attention, naming, or figure copying did not differentiate the groups. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Human immunodeficiency virus-Type 1 (HIV-1) and the brain.

Infection with human immunodeficiency virus Type-1 (HIV-1), the causative agent of AIDS, can be associated with central nervous system as well as immune system disease. Advanced AIDS can be complicated by a dementia. Short of frank dementia, many AIDS patients manifest neuropsychological (NP) impairment including disturbance in speeded information processing, abstraction, learning, and recall. Data conflict on whether medically asymptomatic HIV-1 carriers have subtle NP deficits. Variations in tests chosen, criterion specification, and sample selection may all be contributing to disparate results. Longitudinal research is needed, and this should examine representative samples of HIV-1 seropositive individuals for whom approximate date of seroconversion is known and in whom sources of comorbidity (e.g., drug abuse, concurrent infections, CNS injuries) can be specified. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluation of laser and radiofrequency induced dorsal root entry zone lesion for pain control in rats

Thirty-six HIV-1-infected predominantly well-functioning subjects were followed up for one year by repeated neuropsychological, clinical neurological, neuroradiological, and immunological examinations. Changes in cognitive performance related to the severity of HIV-1 infection as well as to neuroradiological or immunological changes were studied. A decline in cognitive speed and flexibility was found in symptomatic subjects (ARC, AIDS). The impairment was especially pronounced in patients with progression of brain atrophy. These findings suggest a brain pathology underlying the cognitive decline in ambulatory outpatients with symptomatic HIV-1 infection. A practice effect was found in asymptomatic subjects (ASX, LAS) and in those with unchanged CT/MRI scans. No systematic relationship was found between cognitive change and immunological change.     

Lymphoproliferative immune function in the Sydney Blood Bank Cohort, infected with natural nef/long terminal repeat mutants, and in other long-term survivors of transfusion-acquired HIV-1 infection

OBJECTIVES: To assess T-helper cell immune function (proliferation) in members of the Sydney Blood Bank Cohort (SBBC) compared with other individuals with transfusion- and sexually acquired HIV-1 infection and with matched HIV-negative controls. DESIGN AND METHODS: Decreasing CD4 counts and T-helper cell function are associated with disease progression. Peripheral blood mononuclear cells (PBMC) from study subjects were assayed for in vitro proliferative responses to HIV-1-derived antigens, recall antigens and alloantigen. T-helper cell function and CD4 counts in members of the SBBC were followed longitudinally. RESULTS: Proliferative responses and CD4 counts from members of the SBBC were similar to or better than those of other transfusion- or sexually-acquired HIV-1-positive long-term non-progressors (LTNP), including the HIV-negative matched SBBC control groups. However, individuals with disease progression had reduced or undetectable proliferative responses to recall antigens but a conserved response to alloantigen; they also had low CD4 counts and low CD4:CD8 ratios. In the SBBC, these immune parameters were usually stable over time. CONCLUSIONS: The unique SBBC with natural nef/long terminal repeat deletions in the HIV-1 genome were genuine LTNP without showing signs of disease progression. They appeared to be a group distinct from the tail-end of the normal distribution of disease progression rates, and may remain asymptomatic indefinitely. The SBBC virus may form the basis of a live attenuated immunotherapeutic or immunoprophylactic HIV vaccine.     

Asymptomatic embolization in subjects with atrial fibrillation not taking anticoagulants: a prospective study

BACKGROUND AND PURPOSE: Embolism is believed to be the major cause of stroke in patients with nonvalvular atrial fibrillation (NVAF). The detection of asymptomatic embolic signals (ES) in individuals with NVAF might allow identification of patients at high risk of stroke and monitoring of therapy in individual subjects. We determined the frequency of asymptomatic ES in patients with NVAF who were not taking warfarin. METHODS: Bilateral transcranial Doppler recordings were made for 1 hour from the middle cerebral arteries of 111 successive patients with NVAF taking aspirin alone or no antithrombotic or anticoagulant therapy. Adequate recordings could be made in 86 patients. In 79 subjects, recordings were performed on a second occasion to study temporal variability. Recordings for a single hour were also made in 30 age-matched control subjects. RESULTS: ES were detected in 13 (15.1%) of NVAF subjects but in no control subjects (P=0.02). ES were detected both in subjects with symptomatic NVAF (4 of 30 [13.1%], P=0.04 versus controls) and asymptomatic NVAF (9 of 56 [16.1%], P=0.02 versus controls). There was no correlation between the presence of ES and smoking status, diabetes, hypertension, aspirin use, aspirin dose, symptomatic status, left atrial size, left ventricular function, or the presence of left atrial thrombus detected on transthoracic echocardiography. Repeating the recording increased the number of patients with ES to 21 (26.6%). On considering the results of both recordings, again there was no association for either recording between the presence of ES and smoking status, diabetes, hypertension, aspirin use, aspirin dose, age, symptomatic status, left atrial size, or left ventricular function. On repeating the recording, in the symptomatic group only 2 patients (8%) changed status, in contrast to 15 (29%) in the asymptomatic group. CONCLUSIONS: ES can be detected in patients with NVAF at a low frequency. Particularly in asymptomatic patients, ES show marked temporal variability. We found no correlation between the presence of previously reported clinical and echocardiographic markers of increased stroke risk and the presence of ES. This association requires further investigation before the clinical utility of this technique in patients with NVAF is decided.     

Evaluating outcome after spinal cord injury: what determines success? 1996 Donald Munro Lecture

OBJECTIVE: To determine the nature and extent of cognitive deficits in early stage (asymptomatic) human immunodeficiency virus (HIV)-positive homosexual and bisexual men. DESIGN: A cross-sectional design was used to compare 27 HIV-positive, asymptomatic (Centers for Disease Control and Prevention stages 2 and 3) homosexual and bisexual men, who were designated as the seropositive group, with 29 seronegative homosexual and bisexual men, who were designated as the control group. METHODS: The participant groups were closely matched on a number of demographic and lifestyle variables. Participants were carefully and repeatedly screened for substance abuse, a history of psychiatric problems, use of psychoactive medications, and neurological problems. All participants completed an extensive neuropsychological battery and a computerized information processing battery to identify cognitive deficits. RESULTS: No significant between-group differences were found on either the neuropsychological assessments or the information processing tests. Additionally, we found no evidence of a subgroup of seropositive, asymptomatic individuals with general cognitive slowing. CONCLUSIONS: Educated, HIV-positive asymptomatic individuals may show little difference in cognitive performance compared with a group of matched controls when the groups are carefully screened and matched. Additionally, computerized tests may be no more sensitive than neuropsychological tests to cognitive decrements for these types of participants.     

Dysregulation of membrane-bound tumor necrosis factor-alpha and tumor necrosis factor receptors on mononuclear cells in human immunodeficiency virus type 1 infection: low percentage of p75-tumor necrosis factor receptor positive cells in patients with advanced disease and high viral load

The correlation of persistent tumor necrosis factor-alpha (TNF-alpha) activation with disease progression in patients infected with human immunodeficiency virus type 1 (HIV-1), suggests a role for TNF-alpha in the pathogenesis of HIV-1 infection. In the present study, we examined by flow cytometry the expression of membrane-bound (m) components of the TNF system in 33 HIV-1-infected patients and 12 healthy controls. While peripheral blood mononuclear cells (PBMC) from asymptomatic and symptomatic non-acquired immune deficiency syndrome (AIDS) patients showed a significantly increased percentage of mTNF-alpha+ and mTNF receptor (TNFR)+ cells compared with controls, this was not found in the AIDS group. Compared with healthy controls, AIDS patients had a significantly decreased percentage of both monocytes and lymphocytes expressing p75-TNFR. PBMC from AIDS patients showed a higher p75-TNFR mRNA level and a higher spontaneous release of soluble p75-TNFR than healthy individuals, suggesting enhanced cell surface turnover of this TNFR. The low expression of TNFRs on both lymphocytes and monocytes in the AIDS group was associated with high numbers of HIV-1 RNA copies in plasma, low numbers of CD4+ lymphocytes, and high serum levels of soluble TNFRs. AIDS patients had a decreased percentage of CD8+ lymphocytes expressing TNFRs compared with healthy controls. In contrast, these patients, as well as symptomatic non-AIDS patients, had an increased percentage of TNF-alpha+ and TNFRs+ cells among remaining CD4+ lymphocytes. The pattern of abnormalities seen in AIDS patients suggests a role for persistent activation of the TNF system in the accelerated CD4+ lymphocyte destruction, the enhanced HIV-1 replication, and the markedly impaired antimicrobial defense in advanced HIV-1-related disease.     

Cognitive estimation impairment in Alzheimer disease and mild cognitive impairment.

Intact executive functioning is believed to be required for performance on tasks requiring cognitive estimations. This study used a revised version of a cognitive estimations test (CET) to investigate whether patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) were impaired on the CET compared with normal elderly controls (NECs). Neuropsychological tests were administered to determine the relationship between CET performance and other cognitive domains. AD patients displayed impaired CET performance when compared with NECs but MCI patients did not. Negative correlations between tests of working memory (WM) and semantic memory and the CET were found in NECs and AD patients, indicating that these cognitive domains were important for CET performance. Regression analysis suggests that AD patients were unable to maintain semantic information in WM to perform the task. The authors conclude that AD patients display deficits in working memory, semantic memory, and executive function, which are required for adequate CET performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)