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Biomedical subjects

Igor Grant

Publications and source records attributed to Igor Grant.

At least 19 recordsLinked to original sources
PubMed2006

Cortical and subcortical neurodegeneration is associated with HIV neurocognitive impairment.

OBJECTIVE: To determine the association of markers of regional neurodegeneration (ND) at autopsy to degree of neurocognitive impairment in persons with HIV. DESIGN: In a prospectively followed cohort of HIV-infected individuals we examined the relationship between antemortem neuropsychological (NP) abilities and postmortem neuropathological data. METHODS: Twenty-seven HIV-infected individuals with both neuropsychological and neuropathological data were identified. Laser confocal scanning microscopy was used to determine the degree of ND based on: (1) microtubule-associated protein (MAP2; reflecting neuronal cell bodies and dendrites) and (2) synaptophysin (SYN; a measure of presynaptic terminals). A regional combined score, based on the distribution of percentage neuropil occupied by MAP2 and SYN and emphasizing severity of ND, was created for each brain region: midfrontal cortex, hippocampus, and putamen. RESULTS: The regional combined scores from each brain region studied were better correlated with level of global NP impairment than measures of SYN and MAP2 individually. In a regression, hippocampal and putamen regional combined scores were independent predictors of degree of antemortem NP impairment (F(3,23) = 6.17; P < 0.01; R2 = 0.45). The correlations among regional ND measures demonstrated that ND is unevenly distributed across multiple brain regions. CONCLUSIONS: As the anatomic distribution and temporal progression of neuropathologic changes appears to differ across individuals, it is important to consider both cortical and subcortical brain regions in studies of neuropathogenesis and treatment of HIV-related brain disease. Furthermore, combining information from several markers of neural injury provided the strongest association with degree of neurocognitive impairment during life.

Adult↗
PubMed2006

Recency effects in HIV-associated dementia are characterized by deficient encoding.

The aim of the present study was to investigate the nature and cognitive mechanisms of serial position learning effects in HIV-associated dementia (HAD). Participants were 16 persons with HAD, 50 non-demented persons with HIV-infection, and 50 demographically comparable HIV-seronegative participants. HAD participants, relative to both comparison groups, exhibited reduced middle region (p<0.01) and elevated recency region (p<0.05) recall on the Hopkins Verbal Learning Test-Revised, but no primacy region effect (p>0.10). On recognition testing, the HAD group was impaired in discriminating targets from distractors (p<0.01) in all three serial position regions; however, they were not impaired on measures of retrieval (p>0.10) within these same regions. In sum, HAD participants relied disproportionately on recency regions of the list, indicating a passive recall style of echoing only the words within their auditory attention span. Interestingly, HAD participants did not evidence significant improvement on measures of recognition, a finding that suggests that the serial position effects are most consistent with a primary encoding deficit.

AIDS Dementia Complex↗
PubMed2006

Additive deleterious effects of methamphetamine dependence and immunosuppression on neuropsychological functioning in HIV infection.

Methamphetamine (MA) dependence and HIV infection are independently associated with cerebral dysfunction, especially within frontal-basal ganglia circuits. Recent evidence indicates that MA dependence has an additive effect on neuropsychological (NP) deficits associated with HIV infection. This study extends prior findings by examining the combined effects of MA dependence (MA+) and immunosuppression (i.e., CD4 lymphocyte count <200) on NP functioning in 284 HIV+ individuals. Prevalence of NP impairment was examined in four demographically comparable groups: (1) MA+/CD4 < 200; (2) MA+/CD4 > or = 200; (3) MA-/CD4 < 200; and (4) MA-/CD4 > or = 200. Results revealed that both MA dependence and immunosuppression were significant predictors of NP impairment. More importantly, additive effects were evident whereby the MA+/CD4 < 200 group exhibited the highest rate of NP impairment. Findings indicate that MA dependence conveys an additive deleterious impact on NP status in immunosuppressed persons with HIV infection, perhaps reflecting the combined effects of neuropathophysiological mechanisms in fronto-striatal circuits.

Adult↗
PubMed2006

Prospective memory in HIV-1 infection.

The cognitive deficits associated with HIV-1 infection are thought to primarily reflect neuropathophysiology within the fronto-striato-thalamo-cortical circuits. Prospective memory (ProM) is a cognitive function that is largely dependent on prefronto-striatal circuits, but has not previously been examined in an HIV-1 sample. A form of episodic memory, ProM involves the complex processes of forming, monitoring, and executing future intentions vis-à-vis ongoing distractions. The current study examined ProM in 42 participants with HIV-1 infection and 29 demographically similar seronegative healthy comparison (HC) subjects. The HIV-1 sample demonstrated deficits in time- and event-based ProM, as well as more frequent 24-hour delay ProM failures and task substitution errors relative to the HC group. In contrast, there were no significant differences in recognition performance, indicating that the HIV-1 group was able to accurately retain and recognize the ProM intention when retrieval demands were minimized. Secondary analyses revealed that ProM performance correlated with validated clinical measures of executive functions, episodic memory (free recall), and verbal working memory, but not with tests of semantic memory, retention, or recognition discrimination. Taken together, these findings indicate that HIV-1 infection is associated with ProM impairment that is primarily driven by a breakdown in the strategic (i.e., executive) aspects of retrieving future intentions, which is consistent with a prefronto-striatal circuit neuropathogenesis.

Adult↗
PubMed2006

Avoidant coping partially mediates the relationship between patient problem behaviors and depressive symptoms in spousal Alzheimer caregivers.

OBJECTIVE: Caring for a loved one with Alzheimer disease is a highly stressful experience that is associated with significant depressive symptoms. Previous studies indicate a positive association between problem behaviors in patients with Alzheimer disease (e.g., repeating questions, restlessness, and agitation) and depressive symptoms in their caregivers. Moreover, the extant literature indicates a robust negative relationship between escape-avoidance coping (i.e., avoiding people, wishing the situation would go away) and psychiatric well-being. The purpose of this study was to test a mediational model of the associations between patient problem behaviors, escape-avoidance coping, and depressive symptoms in Alzheimer caregivers. METHODS: Ninety-five spousal caregivers (mean age: 72 years) completed measures assessing their loved ones' frequency of problem behaviors, escape-avoidance coping, and depressive symptoms. A mediational model was tested to determine if escape-avoidant coping partially mediated the relationship between patient problem behaviors and caregiver depressive symptoms. RESULTS: Patient problem behaviors were positively associated with escape-avoidance coping (beta = 0.38, p < 0.01) and depressive symptoms (beta = 0.26, p < 0.05). Escape-avoidance coping was positively associated with depressive symptoms (beta = 0.33, p < 0.01). In a final regression analysis, the impact of problem behaviors on depressive symptoms was less after controlling for escape-avoidance coping. Sobel's test confirmed that escape-avoidance coping significantly mediated the relationship between problem behaviors and depressive symptoms (z = 2.07, p < 0.05). CONCLUSION: Escape-avoidance coping partially mediates the association between patient problem behaviors and depressive symptoms among elderly caregivers of spouses with dementia. This finding provides a specific target for psychosocial interventions for caregivers.

Adaptation, Psychological↗
PubMed2006

Personal mastery attenuates the effect of caregiving stress on psychiatric morbidity.

This study examined the protective effects of personal mastery on the relations between both objective and subjective stress and psychiatric morbidity in 79 spousal Alzheimer caregivers. Results indicated that with low mastery, the relations between patient problem behaviors and caregiver psychiatric symptoms was significant (t[71] = 2.03; p = 0.046). However, with high mastery, no significant association was found (t[71] = -0.76; p = 0.452). Similarly, the relations between role overload and psychiatric morbidity was significant when mastery was low (t[71] = 2.22; p = 0.029), but not high (t[71] = -1.49; p = 0.140). These results suggest that caregivers with a greater sense of personal mastery may be protected from the negative effects of caregiver stress.

Caregivers↗
PubMed2006

Work-related abilities in schizophrenia and HIV infection.

Schizophrenia and human immunodeficiency virus (HIV) infection both are associated with high rates of neurocognitive impairment. These impairments predict unemployment in both disorders, independent of other disease-related factors that may affect employment. In this study, we investigated work-related abilities and previous employment patterns in 27 unemployed patients with schizophrenia, 27 demographically matched unemployed HIV-infected participants, and 27 nonmatched employed HIV seropositive (HIV+) participants. All subjects were administered a computerized and hands-on assessment of vocational abilities and a comprehensive work history interview. Compared with the employed HIV+ group, the two unemployed groups had lower estimates of maximal lifetime job functioning. In terms of current vocational abilities, the employed HIV+ subjects generally performed best, followed by the unemployed HIV+ subjects and the patients with schizophrenia. Although the unemployed schizophrenia subjects had the most decline in vocational abilities (from estimated lifetime maximum level), the patterns of decline were similar in the two unemployed groups and were suggestive of parallel impairments in frontal-subcortical functioning.

Adult↗
PubMed2006

Poor sleep is associated with higher plasma proinflammatory cytokine interleukin-6 and procoagulant marker fibrin D-dimer in older caregivers of people with Alzheimer's disease.

OBJECTIVES: To determine whether objective measures of sleep correlate with plasma levels of the proinflammatory cytokine interleukin (IL)-6 and the procoagulant marker fibrin D-dimer in caregivers of patients with dementia. DESIGN: Cross-sectional study. SETTING: Subjects' homes. PARTICIPANTS: Sixty-four community-dwelling spousal caregivers (69% women, mean age+/-standard deviation 72+/-9) and 36 sex-matched noncaregiving controls. MEASUREMENTS: All participants underwent in-home full-night polysomnography. Demographic and lifestyle factors, depression, diseases, and medication that could affect inflammation, coagulation, and sleep were controlled for in analyses regressing sleep variables and caregiver status and their interaction on plasma levels of IL-6 and D-dimer. RESULTS: Caregivers had higher levels of D-dimer (781+/-591 vs 463+/-214 ng/mL, P=.001) and IL-6 (1.42+/-1.52 vs 0.99+/-0.86 pg/mL, P<.06) and lower levels of total sleep time (369+/-70 vs 393+/-51 minutes, P=.049) and sleep efficiency (77+/-11 vs 82+/-9%, P=.04) than controls. After controlling for age and body mass index, longer wake time after sleep onset (change in coefficient of determination (DeltaR2)=0.039, P=.04) and the interaction between caregiver status and higher apnea-hypopnea index (DeltaR2=0.054, P=.01) were predictors of IL-6. Controlling for age, caregiver status independently predicted D-dimer levels (DeltaR2=0.047, P=.01). Controlling for age and caregiver status, lower sleep efficiency (DeltaR2=0.032, P=.03) and the interaction between caregiver status and more Stage 2 sleep (DeltaR2=0.037, P=.02) independently predicted plasma D-dimer levels. CONCLUSION: Poor sleep was associated with higher plasma IL-6 and D-dimer levels. These effects were most pronounced in caregivers of subjects with Alzheimer's disease. The findings suggest a mechanism that may explain how disturbed sleep might be associated downstream with cardiovascular risk, particularly in older people under chronic stress.

Aged↗
PubMed2005

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.

Adult↗
PubMed2005

Construct validity of Hopkins Verbal Learning Test-Revised component process measures in an HIV-1 sample.

Executive dyscontrol of episodic verbal learning and memory secondary to prefrontostriatal circuit neuropathophysiology is a common feature of HIV-1 infection. Prior research indicates that standard clinical learning and recall indexes from Hopkins Verbal Learning Test-Revised (HVLT-R) are among the most sensitive indicators of HIV-associated neurocognitive disorders. Emerging data support the validity of qualitative component process measures derived from the HVLT-R (e.g., Semantic Clustering); however, no prior studies have examined these particular indices of performance in an HIV-1-infected population. In the present study, we examined the construct validity of HVLT-R component process indices in a sample of 42 persons with HIV-1 infection and 29 demographically similar seronegative comparison participants. The HIV-1 sample performed significantly below the seronegative group on Total and Delayed Recall, Semantic Clustering, and the Retrieval Index. No between-group differences were observed on Serial Clustering, Pair Frequency, Learning, Repetitions, Semantic False Positive Recognition Errors, or the Recognition Discrimination Index. In addition, the HVLT-R component process measures demonstrated evidence of convergent and divergent validity with standard clinical tests in the HIV-1 sample. Findings support the construct validity of HVLT-R component process measures and are commensurate with prior literature indicating that HIV-1 disease is associated with deficient executive control of encoding and retrieval within verbal episodic memory.

Adult↗
PubMed2005

A battery approach for measuring neuropsychological change.

The accurate interpretation of serial neuropsychological testing is a fundamental activity of neuropsychologists in clinical and research settings. Although prior research supports the construct validity of several individual tests for the reliable measurement of cognitive change, neuropsychologists are often interested in detecting changes in cognitive functioning across a battery of tests. In the present study, we examined the specificity of a modified Reliable Change Index (RCI) methodology applied across a focused battery of commonly used neuropsychological tests. Fifty-seven healthy controls underwent neuropsychological assessment at two time points separated by approximately 1 year. Test-retest reliability coefficients and standard RCI confidence intervals for the individual tests were broadly comparable with prior research in healthy populations. Battery change scores were generated by calculating z-scores of change for each individual test, which were summed across the entire test battery. The RCI methodology was applied to the summed z-score to provide a 90% confidence interval as an indicator of overall cognitive stability. These battery RCI normative standards demonstrated adequate specificity when applied to 29 persons with HIV-1 infection who were classified as medically and neurologically stable. Findings from this study may be useful for both clinicians and researchers seeking normative standards for determining reliable changes in performance across a commonly used battery of neuropsychological tests.

Adult↗
PubMed2005

Mood disorders in the medically ill: scientific review and recommendations.

OBJECTIVE: The purpose of this review is to assess the relationship between mood disorders and development, course, and associated morbidity and mortality of selected medical illnesses, review evidence for treatment, and determine needs in clinical practice and research. DATA SOURCES: Data were culled from the 2002 Depression and Bipolar Support Alliance Conference proceedings and a literature review addressing prevalence, risk factors, diagnosis, and treatment. This review also considered the experience of primary and specialty care providers, policy analysts, and patient advocates. The review and recommendations reflect the expert opinion of the authors. STUDY SELECTION/DATA EXTRACTION: Reviews of epidemiology and mechanistic studies were included, as were open-label and randomized, controlled trials on treatment of depression in patients with medical comorbidities. Data on study design, population, and results were extracted for review of evidence that includes tables of prevalence and pharmacological treatment. The effect of depression and bipolar disorder on selected medical comorbidities was assessed, and recommendations for practice, research, and policy were developed. CONCLUSIONS: A growing body of evidence suggests that biological mechanisms underlie a bidirectional link between mood disorders and many medical illnesses. In addition, there is evidence to suggest that mood disorders affect the course of medical illnesses. Further prospective studies are warranted.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Impulsivity and methamphetamine use.

The purpose of this study was to explore the relationship between methamphetamine (meth) use and impulsivity in a sample of 385 HIV-negative heterosexually identified meth users. Participants who scored highest on a self-report measure of impulsivity were compared with those who scored lower in terms of background characteristics, meth use patterns, use of alcohol and other illicit drugs, sexual risk behavior, and psychiatric health variables. Methamphetamine users in the high impulsivity group were younger, less educated, used larger quantities of meth, were more likely to be binge users, had a larger number of sexual partners, engaged in more unprotected vaginal and oral sex, and scored higher on the Beck Depression Inventory as compared with those in the low impulsivity group. In a logistic regression analysis, Beck depression was the factor that best distinguished between meth users who scored high and those who scored low on impulsivity. Neurophysiological pathways that may underlie the relationship between impulsivity and meth use are discussed.

Adolescent↗
PubMed2005

Temperament and risky behaviors: a pathway to HIV?

BACKGROUND: Certain sexual behaviors and abuse of substances contribute to the risk of becoming HIV-infected. Because dispositional characteristics are likely to influence this process, we examined the association between temperament and HIV serostatus in subjects with heavy use of drugs and various sexual risk behaviors. METHODS: Two hundred and thirty individuals (81% of whom were HIV-infected) were assessed for underlying temperamental characteristics, substance use, and risky sexual behaviors. Toward this goal, a factor analysis was conducted on a new self-rated Temperament Autoquestionnaire (Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A)). MANOVA was used to examine overall associations between risky behaviors and temperament. Additionally, directed MANOVAs were conducted for each of six drugs of abuse (alcohol, marijuana, cocaine, opioids, other stimulants, and sedative hypnotics). RESULTS: Factor analysis confirmed the hypothesized temperament structure of five distinct factors: Cyclothymic, hyperthymic, anxious, irritable-explosive, and depressive. Heavy users of cocaine, other stimulants, and alcohol were more likely to have an irritable-explosive temperament. Interestingly, heavy users of opioids were more likely to show depressive and hyperthymic traits. The inclusion of HIV status as a predictor of temperament did not alter the results. Unlike a previous study, no direct significant relationships were found between risky sexual behaviors and specific temperaments. LIMITATIONS: Relatively small sample size for a factor analytic study, and cross-sectional design, which cannot determine a cause and effect relationship. CONCLUSIONS: We succeeded in studying and validating five distinct affective temperaments in a substance abuse population. Irritable-explosive, and to a lesser extent, depressive and hyperthymic traits, were associated with substance use, and may place individuals at risk for HIV infection via that mechanism. That current risky sexual practices were not directly linked to temperament may reflect modification in sexual behavior following the acquisition of HIV disease.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Deficient strategic control of verbal encoding and retrieval in individuals with methamphetamine dependence.

Methamphetamine (MA) dependence is associated with deficits in episodic verbal memory, but the cognitive mechanisms underlying such impairments are not known. The authors evaluated a component process model of episodic verbal memory in 87 persons with MA dependence (MA+) and 71 demographically similar non-MA-using controls (MA-). Compared with MA- controls, MA+ participants demonstrated deficient overall learning, free recall, and utilization of semantic clustering, as well as higher rates of repetitions and intrusions. No between-groups differences were evident on measures of serial clustering, retention, or recognition discrimination. Taken together, these findings indicate that MA dependence is associated with deficient strategic (i.e., executive) control of verbal encoding and retrieval, which is consistent with the sequelae of MA-related prefronto-striatal circuit neurotoxicity.

Adult↗
PubMed2005

Negative self-perceptions and sexual risk behavior among heterosexual methamphetamine users.

This research examined the relationship between negative self-perceptions and sexual risk behavior in a sample of 156 heterosexually identified, methamphetamine users from San Diego, California. The Beck Depression Inventory and the Self Esteem Rating Scale, respectively, were used to assess depression and negative self-perceptions. Measures of sexual risk behavior and methamphetamine use were developed specifically for this research. Data were gathered in 2001-2002. Participants were primarily male (76%), Caucasian (56%), never married (51%), and unemployed (73%), with a mean age of 39.1 years. Participants with high levels of negative self-perceptions evidenced the greatest degree of sexual risk behavior, including significantly more unprotected vaginal sex and a larger number of sexual partners as compared to individuals with low levels of negative self-perceptions. In cross-sectional analyses, negative self-perceptions predicted intensity of methamphetamine use and depressive symptoms. However, neither of these variables were found to mediate the relationship between negative self-perceptions and sexual risk behavior. Findings are discussed in relation to the need for further research into the role of negative self-perceptions as a determinant of sexual risk behavior among methamphetamine users.

Adolescent↗