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Biomedical subjects

Igor Grant

Publications and source records attributed to Igor Grant.

At least 73 records · Page 4Linked to original sources
PubMed2004

Methamphetamine dependence increases risk of neuropsychological impairment in HIV infected persons.

Both HIV infection and methamphetamine dependence can be associated with brain dysfunction. Little is known, however, about the cognitive effects of concurrent HIV infection and methamphetamine dependence. The present study included 200 participants in 4 groups: HIV infected/methamphetamine dependent (HIV+/METH+), HIV negative/methamphetamine dependent (HIV-/METH+), HIV infected/methamphetamine nondependent (HIV+/METH-), and HIV negative/methamphetamine nondependent (HIV-/METH-). Study groups were comparable for age, education, and ethnicity, although the HIV-/METH- group had significantly more females. A comprehensive, demographically corrected neuropsychological battery was administered yielding a global performance score and scores for seven neurobehavioral domains. Rates of neuropsychological impairment were determined by cutoff scores derived from performances of a separate control group and validated with larger samples of HIV+ and HIV- participants from an independent cohort. Rates of global neuropsychological impairment were higher in the HIV+/METH+ (58%), HIV-/METH+ (40%) and HIV+/METH- (38%) groups compared to the HIV-/METH- (18%) group. Nonparametric analyses revealed a significant monotonic trend for global cognitive status across groups, with least impairment in the control group and highest prevalence of impairment in the group with concurrent HIV infection and methamphetamine dependence. The results indicate that HIV infection and methamphetamine dependence are each associated with neuropsychological deficits, and suggest that these factors in combination are associated with additive deleterious cognitive effects. This additivity may reflect common pathways to neural injury involving both cytotoxic and apoptotic mechanisms.

Adult↗
PubMed2004

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.

Activities of Daily Living↗
PubMed2004

Retrograde amnesia in dementia: comparison of HIV-associated dementia, Alzheimer's disease, and Huntington's disease.

Remote memory was assessed in persons with HIV-associated dementia (HIV-D), probable Alzheimer's disease (AD), and Huntington's disease (HD) and in healthy controls. The clinical groups were similar in overall dementia severity. Each clinical group exhibited impairments on remote memory tests relative to controls; however, temporally graded memory loss with selective preservation of older information was observed in the AD group but not the HD or HIV-D group. Analysis of cued retrieval indicated a preferential cuing benefit for the HIV-D and HD groups relative to the AD group. The similar pattern of remote memory performance demonstrated by the HIV-D and HD groups is a novel finding and suggests a subcortically mediated retrograde amnesia in HIV-D. The temporally graded pattern and the abnormal cued retrieval performance in the AD group are consistent with a consolidation deficit associated with extrahippocampal (cortical) and hippocampal damage.

AIDS Dementia Complex↗
PubMed2004

The relationship between AIDS retinal cotton wool spots and neuropsychological impairment in HIV-positive individuals in the pre-highly active antiretroviral therapy era.

PURPOSE: To determine the relationship between AIDS retinal cotton wool spots (CWS) and neuropsychological impairment in HIV-positive individuals in the pre-HAART (highly active anti-retroviral therapy) era and the association between AIDS-related retinal CWS and neuropsychological impairment in HIV-positive patients not treated with HAART. METHODS: A case-control analysis of prospectively acquired data in HIV-infected individuals who underwent prospective and longitudinal evaluations of retinal findings as well as neuropsychological testing was performed. Individuals underwent prospective retinal ophthalmic examinations with fundus photography of any retinal lesions. They also underwent periodic neuropsychological testing. The occurrence of retinal CWS was analyzed in relationship to neuropsychological impairment. RESULTS: Thirty individuals with CWS were compared to 6o matched control AIDS patients. There was no association between either global clinical neuropsychological impairment or impairment in any of the five major domains tested and retinal CWS. There was an association between beta-2 microglobulin and CWS as well as an association between low CD4 T-cell count and the presence of retinal CWS. CONCLUSIONS: We found no association between retinovascular disease and neurocognitive impairment in this case-control study. Retinal CWS in HIV disease are related to higher serum beta-2 microglobulin levels and lower CD4 T-cell counts, suggesting that these lesions are related to HIV disease progression but may be caused by a pathological process independent of CNS disease.

AIDS Dementia Complex↗
PubMed2004

Interrater reliability of clinical ratings and neurocognitive diagnoses in HIV.

We examined the interrater (IRR) of clinical ratings of neuropsychological (NP) impairment and neurocognitive diagnoses in HIV. Thirty participants with advanced HIV-infection who were enrolled in a multicenter HIV brain banking research project underwent comprehensive NP and neuromedical evaluations. Using a standardized system of guidelines, neuropsychologists from six participating sites independently assigned clinical ratings of NP impairment, as well as multilevel diagnoses reflecting the inferred etiology of the impairments and their effects on everyday functioning. Findings indicated excellent IRR in rating the presence and severity of NP impairment, but overall modest IRR for neurocognitive diagnoses. Not surprisingly, most diagnostic disagreements concerned the etiology of impairments in persons with medical and neuropsychiatric risk factors in addition to HIV.

Adult↗
PubMed2004

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.

Adult↗
PubMed2004

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.

Adult↗
PubMed2004

Female methamphetamine users: social characteristics and sexual risk behavior.

The primary objective of this research was to expand our knowledge regarding the personal and social characteristics of female methamphetamine (meth) users, their motivations for using meth, patterns of meth use, medical and social problems associated with meth use, and the relationship between meth use and sexual risk behaviors. The sample consisted of 98 HIV-negative, heterosexually-identified, meth-using females residing in San Diego, California. Female meth users were characterized by personal and social disadvantage, high rates of psychiatric symptomatology, and high levels of sexual risk behavior, including multiple partners, risky partner types (e.g., anonymous sex partners), and high rates of unprotected vaginal and oral sex. Meth use was also associated with the subjective positive experience of sex. These finding suggest that behavioral interventions should be tailored to the social characteristics of female meth users, and program content should reflect the intertwining of women's sexual experience and meth use.

Adult↗
PubMed2003

Patterns of selective neuronal damage in methamphetamine-user AIDS patients.

The risk for HIV infection attributable to methamphetamine (METH) use continues to increase. The combined effect of HIV and METH in the pathogenesis of HIV encephalitis (HIVE) is unclear, however. To better understand the neuropathology associated with HIV and METH use, the patterns of neurodegeneration were assessed in HIV-positive METH users and in HIV-positive non-METH users. Patients in the study met criteria for inclusion and received neuromedical and postmortem neuropathologic examinations. Immunocytochemical and polymerase chain reaction analyses were performed to determine brain HIV levels and to exclude the presence of other viruses. METH-using patients with HIVE showed significantly lower gp41 scores and less severe forms of encephalitis but a higher frequency of ischemic events, a more pronounced loss of synaptophysin immunoreactivity, and a more severe microglial reaction than HIVE non-METH users. Furthermore, in METH-using patients with HIVE, extensive loss of calbindin (CB)-immunoreactive interneurons displaying phylopodial neuritic processes suggestive of aberrant sprouting was observed. Taken together, these studies indicate that the combined effects of METH and HIV selectively damage CB immunoreactive nonpyramidal neurons. In combination, METH and HIV may increase neuronal cell injury and death, thereby enhancing brain metabolic disturbances observed in clinical populations of HIV-positive METH abusers.

AIDS Dementia Complex↗
PubMed2003

Increased human immunodeficiency virus loads in active methamphetamine users are explained by reduced effectiveness of antiretroviral therapy.

Abuse of methamphetamine (METH) is a frequent comorbidity among individuals infected with human immunodeficiency virus (HIV) type 1. In cell cultures and animal models, METH accelerates retroviral replication. To determine whether METH increases HIV replication in humans, we evaluated HIV loads in HIV-positive METH users and nonusers. We studied 3 groups: Tox+, active METH use and positive urine toxicology results; METH(+)Tox-, previous METH dependence/abuse and negative urine toxicology results; METH(-)Tox-, no METH dependence/abuse and negative urine toxicology results. Tox+ subjects' plasma virus loads were significantly higher than METH(+)Tox- and METH(-)Tox- subjects'; cerebrospinal fluid virus loads showed a similar but nonsignificant trend. Stratification by use of highly active antiretroviral therapy (HAART) revealed that virus loads were higher only in those Tox+ subjects who reported receiving HAART. In contrast, abstinent former METH abusers (METH(+)Tox-) receiving HAART effectively suppressed viral replication. These data suggest that abstinence programs are a key component of effective treatment of HIV in METH-abusing populations.

Anti-HIV Agents↗
PubMed2003

Deriving heart period variability from blood pressure waveforms.

International standards for calculating heart period variability (HPV) from a series of R-wave intervals (R-R) in an electrocardiographic (ECG) recording have been widely accepted. It is possible, and potentially useful in various settings, to use systolic blood pressure waveform intervals to estimate HPV, but the validity of HPV derived from blood pressure (BP) waveforms has not been established. To test the reliability between BP- and ECG-derived HPV indexes, we evaluated data from 234 healthy adults in four studies of HPV reactivity to stress. Study conditions included resting baseline, arithmetic, Stroop test, speech presentation, and orthostatic tilt. Continuous ECG and BP recordings were sampled at a rate of 500 Hz, scored by the same methods, and used to calculate heart rate and time- and frequency-domain measures of HPV. Overall, reliability between the two methods was very high for computing heart rate and HPV indexes. High-frequency HPV indexes were somewhat less reliably computed. In conclusion, in healthy adults, with the use of appropriate methods, BP waveforms can produce reliable indexes of HPV.

Adult↗
PubMed2003

Prediction of incident neurocognitive impairment by plasma HIV RNA and CD4 levels early after HIV seroconversion.

BACKGROUND: Neuropsychological (NP) impairment is a relatively common sequela in human immunodeficiency virus (HIV)-infected individuals with advanced disease. Early antecedents of NP dysfunction, however, remain poorly understood. OBJECTIVE: To determine whether early markers of immunocompetence and viral replication in individuals who have undergone seroconversion would be of prognostic value in identifying subjects who would become cognitively impaired. METHODS: Seventy-four subjects with estimable seroconversion dates and normal cognition at baseline (a median of 1 year after seroconversion) received NP and laboratory evaluations, including reverse transcription-polymerase chain reaction measurements of plasma (N = 74) and cerebrospinal fluid (n = 47) levels of HIV RNA. Subjects were followed up longitudinally, and were considered to have reached the end point if they became cognitively impaired. RESULTS: Using Kaplan-Meier estimates, the subgroups with the most rapid progression to NP impairment were (1) subjects with early reductions in CD4 counts (<400 cells/microL at baseline; P =.007) and (2) those with elevated plasma HIV RNA values (>4.5 log10 copies/mL; P =.03) early after seroconversion. Using proportional hazards modeling, the highest-risk subjects had both CD4 counts less than 400 cells/microL and HIV RNA levels greater than 4.5 log10 copies/mL (risk ratio, 6.0; P =.01). In most subjects (7/9 [78%]), NP impairment developed before an acquired immunodeficiency syndrome-defining illness. CONCLUSIONS: Neurocognitive outcomes in HIV are strongly influenced by very early systemic virological and immunological events. Patients with high plasma levels of HIV RNA and low CD4 counts early after infection should be aggressively treated to prevent immunological decline and NP deterioration.

Adult↗
PubMed2003

Emotional expressiveness, hostility and blood pressure in a longitudinal cohort of Alzheimer caregivers.

OBJECTIVE: To assess the interactive effect of chronic stress and emotional expressiveness (EE) on blood pressure (BP) in older adults. METHOD: Among spousal caregivers (n=111) of Alzheimer's disease (AD) patients, BP was assessed at home by a visiting nurse every 6 months for 7 years. Caregiving demands, EE, social desirability and hostility were also assessed. RESULTS: State hostility was more prevalent among newer caregivers and those encountering more dementia problem behaviors and ADL limitations but unrelated to BP or BP change (P>.05). In a cross-sectional analysis, higher diastolic BP was associated with more spousal problem behaviors and being less emotionally expressive (P<.05). Longitudinal (growth curve analysis) increases in diastolic BP were predicted by providing more spousal ADL assistance (P<.05) but not by EE. CONCLUSION: Both caregiving stress and low EE may contribute independently to hypertension risk in the elderly.

Activities of Daily Living↗
PubMed2003

Computerized reaction time battery versus a traditional neuropsychological battery: detecting HIV-related impairments.

In recent years, interest in the use of computerized neuropsychological (NP) assessment measures has increased. However, there are limited data regarding how performance on these measures relates to performance on more traditional, clinical instruments. In the present study, 82 HIV+ men, who were all believed on clinical grounds to have neurobehavioral impairment, completed a traditional NP battery (TNB) and the California Computerized Assessment Package (CalCAP, a collection of computerized reaction time tests). Summary scores based on a TNB, as well as those based on the CalCAP, demonstrated significant associations with both degree of immunosuppression (CD4 count) and detectable viral load in cerebrospinal fluid, but not with detectable viral load in plasma. Established norms on the TNB and CalCAP batteries resulted in classifying 57% and 49% of the HIV+ sample as impaired, respectively. When using the TNB as the "gold standard," impairment classifications based on CalCAP summary scores exhibited a sensitivity of 68% and a specificity of 77%. Overall agreement on impairment classifications between batteries was low (kappa = .44). Data from this study suggest that traditional NP batteries and computerized reaction time tests do not measure the same thing, and are not interchangeable in examining HIV-related NP impairments.

AIDS Dementia Complex↗
PubMed2003

Non-acute (residual) neurocognitive effects of cannabis use: a meta-analytic study.

The possible medicinal use of cannabinoids for chronic diseases emphasizes the need to understand the long-term effects of these compounds on the central nervous system. We provide a quantitative synthesis of empirical research pertaining to the non-acute (residual) effects of cannabis on the neurocognitive performance of adult human subjects. Out of 1,014 studies retrieved using a thorough search strategy, only 11 studies met essential a priori inclusion criteria, providing data for a total of 623 cannabis users and 409 non- or minimal users. Neuropsychological results were grouped into 8 ability domains, and effect sizes were calculated by domain for each study individually, and combined for the full set of studies. Using slightly liberalized criteria, an additional four studies were included in a second analysis, bringing the total number of subjects to 1,188 (i.e., 704 cannabis users and 484 non-users). With the exception of both the learning and forgetting domains, effect size confidence intervals for the remaining 6 domains included zero, suggesting a lack of effect. Few studies on the non-acute neurocognitive effects of cannabis meet current research standards; nevertheless, our results indicate that there might be decrements in the ability to learn and remember new information in chronic users, whereas other cognitive abilities are unaffected. However, from a neurocognitive standpoint, the small magnitude of these effect sizes suggests that if cannabis compounds are found to have therapeutic value, they may have an acceptable margin of safety under the more limited conditions of exposure that would likely obtain in a medical setting.

Cannabis↗
PubMed2003

Base rate of Hiscock Digit Memory Test failure in HIV-associated neurocognitive disorders.

There is an emergent need for base rate data on symptom validity tests (SVTs) in clinical populations that are likely to seek disability benefits. The inclusion of HIV under the Americans with Disabilities Act has prompted many persons with HIV-1 infection to apply for disability, which raises the concern that a subset of these individuals might feign cognitive deficits to obtain benefits. This brief report provides base rate data on one SVT, the Hiscock Digit Memory Test (HDMT), in a sample of 82 non-compensation-seeking, neuropsychologically impaired participants who met diagnostic criteria for an HIV-associated neurocognitive disorder. Approximately 98% of individuals with HIV-associated neurocognitive disorders performed above an established HDMT cutoff for suboptimal effort (i.e., HDMT> or =90% accuracy), whilst 95% of the sample obtained perfect scores. Clinicians can therefore be confident that, in the absence of severe dementia or amnesia, HDMT scores below standard cutoffs are unlikely to be solely attributable to HIV-associated cognitive impairment.

Adult↗
PubMed2003

The functional impact of HIV-associated neuropsychological impairment in Spanish-speaking adults: a pilot study.

Among English-speaking adults, HIV-associated neuropsychological (NP) impairments have been associated with problems in everyday functioning, including ability to function at work and drive an automobile. Latinos account for a disproportionate number of HIV/AIDS cases nationwide, and a significant segment of this population is primarily Spanish speaking. We have previously developed an assessment that evaluates English-speakers on a variety of instrumental activities of daily living. In this pilot study, we used Spanish-language translations of our functional battery to investigate the cultural relevance of such measures, and to explore relationships between NP status and ability to perform important everyday tasks in HIV-infected Spanish-speakers. Sixteen HIV-infected monolingual Spanish-speaking adults received comprehensive, Spanish language NP testing and functional assessments included the following domains: Medication Management, Cooking, Finances, Shopping, and Restaurant Scenario. Results revealed that most of the functional tasks appeared culturally relevant and appropriate with minor modifications. NP-impaired participants were significantly more functionally impaired compared to NP-normals (88% vs. 13%, p <.01). Performances on the functional assessment and the NP battery were also related to indicators of real world functioning, including employment status and quality of life. These results, though preliminary, suggest that Spanish language functional assessments are potentially valid tools for detecting everyday functioning deficits associated with NP impairments in HIV-infected Spanish-speakers.

AIDS Dementia Complex↗