Methamphetamine stimulates interferon inducible genes in HIV infected brain

OBJECTIVE: To study the synergism of HIV and methamphetamine. DESIGN AND METHODS: We undertook a microarray study using RNA from the frontal cortex of 15 individuals with HIV infection to initially identify genes that are differentially regulated by HIV encephalitis (HIVE). From the analysis of the microarray data, we identified candidate genes to be validated by quantitative real time PCR (qRT-PCR) and to assess if these genes were differentially modulated in individuals with HIVE and documented methamphetamine use. RESULTS: Analysis of microarray data revealed that genes involved in several categories were dysregulated in HIVE. We then chose 15 candidate genes for validation by qRT-PCR and analyzed the tissue concentration of these genes across three groups: those with HIV infection and no brain pathology, those with HIVE, and those with both HIVE and a history of methamphetamine use. We noted that there was upregulation of interferon inducible genes in the HIVE with methamphetamine using group, which together as a gene group was highly statistically significant (p=0.0064). CONCLUSION: These findings indicate that dysregulation of interferon inducible genes may underlie the pathogenic mechanism resulting in greater neurodegenerative and neurocognitive burden that occurs in methamphetamine using HIV infected individuals.     

The relationship between employment and neuropsychological impairment in HIV infection.

The relationship between neurocognitive impairment and employment in a cohort of 130 predominantly symptomatic individuals with HIV-1 infection was examined. Participants were classified as employed (full or part-time for pay) or unemployed (N = 64) and administered a neuropsychological test battery. When covarying for CD4 count, age, and physical limitations, the results revealed that unemployed men performed below that of employed participants on tasks of memory, set shifting-cognitive flexibility, and psychomotor speed. The results are discussed within the context of similar findings in other illnesses.     

Methamphetamine dependence is associated with neurocognitive impairment in the initial phases of abstinence

This study documented the association between neurocognitive impairment and methamphetamine dependence in a sample of 27 methamphetamine-dependent individuals who achieved 5 to 14 days of continuously monitored abstinence and in 18 control subjects. Methamphetamine-dependent individuals performed significantly worse than control subjects on neurocognitive measures sensitive to attention/psychomotor speed, on measures of verbal learning and memory, and on executive systems measures sensitive to fluency. These findings are the first to demonstrate that methamphetamine dependence is associated with impairments across a range of neurocognitive domains in a sample of users whose abstinence was continuously monitored with the use of urine screening.     

Predictive validity of global deficit scores in detecting neuropsychological impairment in HIV infection

The current study explored the predictive validity of the Global Deficit Score (GDS) approach in summarizing neuropsychological (NP) test results, and specifically in detecting HIV-associated cognitive impairment. A comprehensive NP test battery was administered to 88 HIV+ subjects and 61 healthy HIV- controls comparable for age, education, and ethnicity. Demographically corrected test data were converted to a GDS, which simulates clinicians' ratings by quantifying the number and degree of impaired performances throughout the test battery while attaching relatively less significance to superior performances and/or those within normal limits. Our results indicated that the GDS approach effectively discriminated HIV+ and normal control groups, and accurately classified HIV+ individuals with NP impairment based on the "gold standard" clinical rating approach. Consistent with previous studies using different subject samples and different NP test batteries, the GDS cutpoint of >or=0.50 yielded optimal balance between sensitivity and specificity in classifying NP impairment, thus supporting the generalizability of the method. Moreover, the ability of the GDS to predict NP impairment across several cutpoints was quite strong, with positive predictive power values ranging from 0.71 to 1.00. These findings support the validity of the GDS as a clinically useful way of summarizing results on NP testing.     

Season of birth and neuropsychological impairment in schizophrenia.

Repeated studies suggest a relationship between winter birth and increased incidence of schizophrenia. Furthermore, there may be seasonal fluctuations in schizophrenia risk factors (e.g., influenza epidemics) and the severity of biological anomalies (e.g., enlarged cerebral ventricles in neuroimaging studies). In order to assess whether winter-born schizophrenics show greater neuropsychological impairment, 112 males meeting Research Diagnostic criteria for schizophrenia were administered the Luria-Nebraska Neuropsychological Battery, a thorough measure of higher cortical functioning deficit. Sixty-four of these 112 patients were also administered the Wechsler Adult Intelligence Scale-Revised, the Benton Visual Retention Test, and the Rey Auditory Verbal Learning Test. Despite the use of several definitions of winter and nonwinter birth, there was no evidence of elevated rates of neuropsychological dysfunction among winter-born patients on any measure. The current study contains certain limitations (e.g., variable medication status at testing), but the results suggest no strong season of birth relationship with neuropsychological impairment in a reasonably large, research-diagnosed sample of schizophrenic patients.     

Neurological soft signs in persons with amnestic mild cognitive impairment and the relationships to neuropsychological functions

ABSTRACT: BACKGROUND: Neurological abnormalities have been reported in persons with amnestic mild cognitive impairment (aMCI). The current study aimed to examine whether neurological soft signs (NSS) could serve as neurological marker of aMCI detection. METHODS: Twenty-nine persons with aMCI and 28 cognitively normal elderly participants were recruited for the present study. The NSS subscales (motor coordination, sensory integration, and disinhibition) of the Cambridge Neurological Inventory and a set of neuropsychological tests were administered to all participants. RESULTS: Persons with aMCI exhibited significantly more motor coordination signs, disinhibition signs, and total NSS than normal controls. Correlation analysis showed that the total score of NSS and motor coordination subscale score were significantly negatively correlated with the combined Z-score of neuropsychological tests in aMCI group. CONCLUSIONS: To some extent, these findings indicated that NSS and neuropsychological tests might reflect some similar information of the brain functioning. The current results suggest that NSS may serve as a potential neurological marker for the early detection of aMCI.     

Presymptomatic neuropsychological impairment in Huntington's disease

Ten asymptomatic individuals at risk for Huntington's disease (HD) were determined by the use of linked DNA probes to have a high (HD+ group) or low (HD- group) probability of having inherited the mutant gene. Neuropsychological examination, performed without knowledge of DNA results, revealed impairments in five of seven subjects in the HD+ group. Abnormalities were related to visuospatial abilities or to functions associated with the frontal lobes. All three subjects in the HD- group showed no neuropsychological impairment. Statistical analyses confirmed differences between the HD+ and HD- groups. Affected parents of subjects were at least 12 years older at symptom onset. These results demonstrate that clear neuropsychological impairment may be present in HD even when overt signs and symptoms are not expected for a number of years.     

Physical activity and risk of cognitive impairment and dementia in elderly persons

CONTEXT: Dementia is common, costly, and highly age related. Little attention has been paid to the identification of modifiable lifestyle habits for its prevention. OBJECTIVE: To explore the association between physical activity and the risk of cognitive impairment and dementia. DESIGN, SETTING, AND SUBJECTS: Data come from a community sample of 9008 randomly selected men and women 65 years or older, who were evaluated in the 1991-1992 Canadian Study of Health and Aging, a prospective cohort study of dementia. Of the 6434 eligible subjects who were cognitively normal at baseline, 4615 completed a 5-year follow-up. Screening and clinical evaluations were done at both waves of the study. In 1996-1997, 3894 remained without cognitive impairment, 436 were diagnosed as having cognitive impairment-no dementia, and 285 were diagnosed as having dementia. MAIN OUTCOME MEASURE: Incident cognitive impairment and dementia by levels of physical activity at baseline. RESULTS: Compared with no exercise, physical activity was associated with lower risks of cognitive impairment, Alzheimer disease, and dementia of any type. Significant trends for increased protection with greater physical activity were observed. High levels of physical activity were associated with reduced risks of cognitive impairment (age-, sex-, and education-adjusted odds ratio, 0.58; 95% confidence interval, 0.41-0.83), Alzheimer disease (odds ratio, 0.50; 95% confidence interval, 0.28-0.90), and dementia of any type (odds ratio, 0.63; 95% confidence interval, 0.40-0.98). CONCLUSION: Regular physical activity could represent an important and potent protective factor for cognitive decline and dementia in elderly persons.     

HIV risk factors for persons with serious mental illness

HIV risk factors were assessed among 120 persons in treatment for serious mental illness. Although subjects had good general knowledge regarding HIV, many engaged in high risk behaviors. Condom use was infrequent among those who had multiple sexual partners, and sharing needles was common for those who used IV drugs. Clearly, factual knowledge about HIV was not sufficient to prevent risky behavior. Nearly half of the sample was categorized as at medium to high risk, and almost half of the participants, especially those at medium risk, underestimated their own level of risk. The results suggest that education and intervention strategies should focus on increasing the accuracy of the individual's risk assessment as well as changing attitudes towards condoms and improving skills in using condoms. Assessing personal risk and adopting risk-reduction strategies are the keys to successful AIDS prevention for persons with serious mental illness.Michael D. Knox is Professor and Chair of the Department of Community Mental Health at the University of South Florida's Florida Mental Health Institute. He also serves as Director of the USF Center for HIV Education and Research. Timothy L. Boaz is Associate Professor in the Department of Community Mental Health. Martha A. Friedrich is Assistant Professor in the Department of Community Mental Health and Associate Director of the USF Center for HIV Education and Research. Michael G. Dow is Associate Professor and Director of Research in the Department of Community Mental Health.This research was funded in part through contract #91MF57230401D with the National Institute of Mental Health. The support and guidance of Armand Checker and Juan Ramos, National Institute of Mental Health, is appreciated.     

Magnetic resonance imaging correlates of neuropsychological impairment in multiple sclerosis.

The authors examined whether specific neuropsychological abnormalities in multiple sclerosis (MS) are associated with focal lesion areas detected by MRI. Lesion area, regardless of distribution, correlated with performance on the vast majority of neuropsychological procedures. No significant difference appeared between groups with normal/mild and moderate overall cognitive impairment on any of the MRI measures. However, patients with severe cognitive impairment had greater lesion area, regardless of location, and had significant atrophy of the corpus callosum compared with the other two groups. These results suggest that severe atrophy of the corpus callosum reflects global disease and provides a relatively focal morphological marker of severe cognitive impairment in MS.     

Evaluation of practice effect on neuropsychological measures among persons with and without HIV infection in northern India

An evaluation of the effects of HIV infection on neurocognition over time is important for understanding disease progression. Changes in cognitive function can be evaluated longitudinally by using neuropsychological testing at repeated intervals. The assessment of change over time, however, is complicated by the potentially confounding influence of learning on repeated test administrations, often referred to as practice effect. In this study, we present data on testing of persons with or without HIV infection on a battery administered at study baseline and repeated 1 year later. Results suggest that practice effects may be diminished in persons with HIV infection compared to without it. This appears to be true even among those with relatively intact immune functioning as measured by CD4 count.     

The impact of HIV-associated neuropsychological impairment on everyday functioning.

HIV-1 infection can be associated with neuropsychological (NP) deficits ranging from subtle to severe. The purpose of this study was to evaluate the functional, or "real-world" impact of HIV-associated NP impairment in a group of 267 HIV-infected participants. All participants received comprehensive NP, neuromedical, and standardized functional evaluations that included laboratory measures of shopping, cooking, financial management, medication management and vocational abilities. Compared to NP-normal participants, those with NP impairment performed significantly worse on all laboratory measures of everyday functioning. Multivariate analyses revealed that the NP ability domains of Abstraction/Executive Function, Learning, Attention/Working Memory and Verbal abilities most strongly and consistently predicted failures on the functional battery. Both NP impairment and impairment on the functional battery were significantly associated with subjective experiences of cognitive difficulties, as well as unemployment and increased dependence in activities of daily living; multivariate prediction models that also considered depressed mood and biological measures of disease progression revealed that impairment on the functional battery and depression were the only unique predictors of all three indicators of "real-world" functioning. The current results add to growing evidence concerning the clinical significance of HIV-associated NP impairment. Objective, laboratory based functional measures, such as those used here, may compliment NP testing in future studies directed at understanding the impact on life quality of central nervous system disorders and their treatments. Finally, there is a need for additional research investigating the apparently independent effect of depression on level of everyday functioning in HIV infected persons.     

A pilot study of cognition and creativity among persons with HIV disease referred for neuropsychological evaluation

Journal of NeuroVirology - Creativity can help people to innovate, overcome obstacles, and successfully navigate challenges in daily life. Some aspects of creativity rely on the prefrontostriatal...     

Profile of neuropsychological impairment in Sleep-related Hypermotor Epilepsy

ObjectiveThe aim of this study was to characterize the neuropsychological features of a representative sample of Sleep-related Hypermotor Epilepsy (SHE) patients and to highlight clinical associations.MethodsThis cross-sectional study included 60 consecutive patients with video/video-electroencephalography–documented SHE. All were assessed by measures of intelligence. Individuals with normal scores underwent a standardized battery of tests. The Fisher exact test and Wilcoxon rank-sum test for statistical analysis.ResultsMean total IQ was 96.96 ± 21.50, with significant differences between verbal and performance scores (p < 0.0001). Nine patients (15%) had intellectual disability (ID)/cognitive deterioration. Of the 49 assessed by the extensive battery, 23 (46.9%) showed deficits in at least one test evaluating phonemic fluency (24.5%), memory (24.5%), inhibitory control (22.4%), or working memory (10.2%). Patients with mutations in SHE genes had lower IQ than patients without mutations, irrespective of the specific gene (p = 0.0176). Similarly, pathological neurological examination (NE) and “any underlying brain disorder” (at least one among pathological NE, abnormal brain magnetic resonance imaging findings, perinatal insult) were associated with ID (p = 0.029, p = 0.036). A higher seizure frequency at last assessment and poor prognosis correlated with worse scores in visuo-spatial memory (p = 0.038, p = 0.040) and visuo-spatial abilities (p = 0.016). Status epilepticus (p = 0.035), poor response to antiepileptic drugs (p = 0.033), and poor prognosis (p = 0.020) correlated with lower shifting abilities, whereas bilateral convulsive seizures correlated with worse working memory (p = 0.049).ConclusionIn all, 53.3% of SHE patients had neuropsychological deficits. The profile of impairment showed worse verbal IQ, as well as deficits in extrafrontal and selective frontal functions. Our data support the contribution of genetics in ID by different biological mechanisms. Variables of clinical severity affect memory and executive functioning.     

Predictors of neuropsychological impairment in seizure-free epilepsy patients

Persons with epilepsy are at increased risk of cognitive deficits as a result of various factors like etiology, structural brain lesions, seizure frequency, seizure type, age at onset of epilepsy, hereditary factors, psychosocial factors, and possible adverse effects of antiepileptic drugs (AEDs). Despite the fact that the majority of epilepsy patients are seizure-free, previous studies on the relationship between epilepsy-related variables and cognitive function have mainly been conducted on patients with persisting seizures. In this study 158 adults with epilepsy on AED monotherapy and without epileptic seizures for at least 2 years were investigated with a neuropsychological test battery in addition to a neurological examination, MRI and EEG. The major findings were that the group had education and employment status similar to the population mean and neuropsychological function in the normal range. In the patient group without idiopathic generalized epilepsy known cerebral etiology was found to be a highly significant predictor of neuropsychological deficit. For patients with idiopathic generalized epilepsy, early seizure debut at < or =18 years was a powerful predictor of neuropsychological impairment.     

Perfusion magnetic resonance imaging correlates of neuropsychological impairment in multiple sclerosis.

Although cognitive impairment is common in multiple sclerosis (MS), its pathophysiology is still poorly understood. Abnormalities of cerebral blood flow (CBF) have long been acknowledged in MS and advances in perfusion magnetic resonance imaging (MRI) allow for their assessment in vivo. We investigated the relationship between regional perfusion changes and neuropsychological (NP) dysfunctions in patients with relapsing-remitting and primary-progressive MS. Absolute CBF, cerebral blood volume (CBV) and mean transit time were measured in 32 MS patients and 11 healthy controls using dynamic susceptibility contrast-enhanced T2(*)-weighted MRI. A comprehensive NP test battery was administered to all patients. A mixed model analysis of covariance was performed for group comparisons in terms of perfusion measures in normal-appearing white matter (NAWM) and deep gray matter (GM). Pearson's correlations were used to describe the association of perfusion metrics with NP Z-scores. CBF and CBV values were significantly decreased in both NAWM and deep GM in MS patients compared with controls (P=0.01). In all patients, deep GM CBF was significantly associated with Rey Complex Figure Test (RCFT)-Copy (r=0.5; P=0.001) and deep GM CBV and NAWM CBV were significantly associated with Color-Word Interference Inhibition Switching test (D-KEFSIS) (r=0.4; P=0.008 and r=0.4; P=0.02). However, the only associations that remained significant after Bonferroni correction were between deep GM CBF and RCFT-Copy (P=0.006), and deep GM CBV and D-KEFSIS (P=0.04). Our results suggest a role for tissue perfusion impairment in NP dysfunction in MS. Large-scale studies are needed to characterize better this association.     

Severity of alcohol dependence and its relationship to neurological soft signs,neuropsychological impairment and family history

We examined the relationship between severity of alcohol dependence, subtle neurological impairment, neuropsychological deficits and genetic vulnerability among 36 day hospital attenders who satisfied the DSM-III-R criteria for alcohol dependence. Severity of alcohol dependence was unrelated to the presence of a family history, but was correlated with neurological soft signs and neuropsychological impairment. Neurological soft signs were correlated with neuropsychological impairment on both Trail A and Trail B. Patients with an affected first-degree relative exhibited more neurological soft signs. These data indicate that severity of alcohol dependence is related not only to neuropsychological impairment, but also to subtle neurological deficits which may not be apparent on conventional neurological examination. Patients with a positive family history of alcohol dependence may be particularly susceptible to the neurological sequelae of alcohol dependence, or may have neurological deficits which antedate their alcohol dependence.     

Relationship between evoked potential and neuropsychological findings in persons “at risk” for Huntington's disease

Abstract

Scalp-recorded evoked potentials (EPs) elicited by left and right median nerve stimulation (LSEP and RSEP), checkerboard pattern flash (VEP), and acoustic click (AEP) were obtained in 40 individuals “at risk” (AR) for Huntington's disease (HD) and 40 nonpatients matched for age, sex, and intelligence. EPs of AR subjects were generally similar to those of nonpatient's overall configuration; however, mean amplitudes were significantly lower for ARs. The lower amplitudes tended to occur primarily among a subgroup of ARs who manifested some degree of cognitive change, as defined by neuropsychological test criteria.     

Early neuropsychological impairment in HIV-seropositive intravenous drug users: evidence from the Italian Multicentre Neuropsychological HIV Study

The aim of the Italian Multicentre Neuropsychological HIV Study is to assess the prevalence and natural history of cognitive deficit in intravenous drug users (IVDUS) during the asymptomatic phase of HIV infection. The study is currently being conducted in four centres (Napoli, Benevento, Verona and Pavia) whose catchment areas are characterized by different levels of prevalence of HIV infection. Cognitive evaluation is being performed by means of a standardized neuropsychological test battery. A total of 251 subjects (167 males and 84 females) have been recruited in the cross-sectional phase of the study, including 75 asymptomatic HIV-seropositive IVDUS (HIV+/IVDUS), 97 HIV-seronegative IVDUS (HIV-/IVDUS) and 79 non-IVDU seronegative controls matched to IVDUS with regard to sex, age and educational level. The prevalence of global cognitive impairment (performance at least 1.5 standard deviations worse than the average of the control group, on at least two out of five tests) was significantly higher in HIV+/IVDUS than in either HIV-/IVDUS (22.7% vs. 8.2%; P<0.01) or healthy controls (22.7% vs. 2.5%; P<0.001). The difference between HIV-/IVDUS and healthy controls was not statistically significant (8.2% vs. 2.5%; P=0.19). The results of this study lend further support to the ‘cerebral reserve’ model. The cerebral reserve could indeed be reduced in IVDUS as a consequence of chronic exposure to the substance of abuse, so that these subjects become more vulnerable to direct and indirect neurotoxic effects of HIV.