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Biomedical subjects

Igor Grant

Publications and source records attributed to Igor Grant.

At least 55 records · Page 3Linked to original sources
PubMed2005

Sleep in spousal caregivers of people with Alzheimer's disease.

STUDY OBJECTIVE: This study examined differences in objective and subjective measures of sleep between caregivers and noncaregivers. DESIGN: Cross-sectional design. SETTING: All assessments were conducted within the home. PARTICIPANTS: Seventy-three community-dwelling spousal caregivers of patients with Alzheimer's disease and 40 noncaregiving controls. MEASUREMENTS AND RESULTS: Subjects completed a semistructured interview on sociodemographics, cognitive status of the care recipient, self-reported sleep quality, and functional outcome. A polysomnogram was conducted. Caregivers of patients with moderate to severe Alzheimer's disease reported significantly more sleep problems (P<.05) and more functional impairment as a result of sleepiness than noncaregivers (P<.01). Objectively, older caregivers of those with moderate to severe Alzheimer's disease slept less than older noncaregivers (P<.05); there were no other significant differences in objective sleep measures. There was a main effect for age, with older caregivers and older noncaregivers having lower sleep efficiency, less slow-wave sleep, and more stage 1 sleep than younger caregivers and noncaregivers (P<.05). CONCLUSIONS: This study suggests that nighttime sleep is shorter but not otherwise disrupted in caregivers of patients with moderate to severe Alzheimer's disease compared with noncaregivers, and the impact of caregiving on sleep disturbance may be most salient for older caregivers. It is possible that these older caregivers are more vulnerable to the effects of sleep disruption and thus have trouble falling back to sleep when the time is afforded them. Future work is needed to examine the differences in care practices in caregivers by age and dementia severity. Perhaps more importantly, studies examining the health consequences of shortened sleep in this group are needed.

Aged↗
PubMed2005

The effects of hepatitis C, HIV, and methamphetamine dependence on neuropsychological performance: biological correlates of disease.

OBJECTIVE: To determine the effects of hepatitis C virus (HCV) infection on neuropsychological (NP) performance. DESIGN: Cross-sectional analysis of a prospectively enrolled cohort. METHODS: A total of 239 HIV-seropositive and 287 HIV-seronegative subjects enrolled in prospective cohort studies at a single center. Subjects underwent standardized assessments, including comprehensive neuropsychological testing, substance use inventory neuromedical examination, venipuncture, and lumbar puncture. HCV antibody was measured in serum. In seropositive individuals, HCV RNA was measured in plasma and cerebrospinal fluid (CSF). RESULTS: HCV-seropositive subjects performed worse on neuropsychological testing and were almost twice as likely to be diagnosed as globally impaired, compared with those who were HCV seronegative. In a multivariate analysis, HCV, HIV, and methamphetamine dependence were independently associated with worse performance, even after adjusting for Centers for Disease Control stage and antiretroviral use. HCV-RNA levels in plasma were higher in those with memory, but not global, impairment. In cerebrospinal fluid, HCV RNA was below 100 copies/ml in all specimens. In HIV-infected subjects, HCV was associated with higher levels of HIV RNA in CSF, but not in plasma. HCV was also associated with higher levels of monocyte chemotactic protein 1, TNF-alpha, and soluble TNF receptor II. HCV-seropositive subjects did not appear to have advanced liver disease. CONCLUSIONS: HIV, HCV, and methamphetamine independently injure the central nervous system, leading to global neuropsychological impairment. HCV may injure the brain by viral or immune-mediated mechanisms. HCV-associated brain injury may be preventable or reversible because HCV infection is potentially curable.

Adult↗
PubMed2005

Effects of methamphetamine dependence and HIV infection on cerebral morphology.

OBJECTIVE: The authors examined the separate and combined effects of methamphetamine dependence and HIV infection on brain morphology. METHOD: Morphometric measures obtained from magnetic resonance imaging of methamphetamine-dependent and/or HIV-positive participants and their appropriate age- and education-matched comparison groups were analyzed. Main effects of age, HIV infection, methamphetamine dependence, and the interactions of these factors were examined in analyses of cerebral gray matter structure volumes. RESULTS: Independent of the effect of age, HIV infection was associated with reduced volumes of cortical, limbic, and striatal structures. There was also some evidence of an interaction between age and HIV infection such that older HIV-positive participants suffered disproportionate loss. Methamphetamine dependence was surprisingly associated with basal ganglia and parietal cortex volume increases, and in one of these structures-the nucleus accumbens-there appeared to be a larger effect in younger methamphetamine abusers. Neurocognitive impairment was associated with decreased cortical volumes in HIV-positive participants but with increased cortical volumes in methamphetamine-dependent participants. CONCLUSIONS: These results suggest significant brain structure alterations associated with both HIV infection and methamphetamine dependence. The regional patterns of the changes associated with these factors were distinct but overlapping, and the effects on brain volumes were opposing. Although the results of the present study provide little information about the specific mechanisms leading to the unexpected methamphetamine effects, they may be related to glial activation or neuritic growth, both of which have been associated with methamphetamine exposure in animal studies. These results have implications for the interpretation of brain morphological findings in methamphetamine-dependent, HIV-positive individuals, a group whose numbers are unfortunately increasing.

Adult↗
PubMed2005

Test-retest reliability of component process variables within the Hopkins Verbal Learning Test-Revised.

Emerging data support the construct validity of component process variables of learning and memory within the Hopkins Verbal Learning Test-Revised (HVLT-R; Brandt & Benedict, 2001); however, the test-retest reliabilities of such measures are heretofore largely unknown. This study reveals generally modest-to-low 1-year test-retest stability for several key HVLT-R component process variables (e.g., semantic clustering) in 41 healthy, younger adults. These findings are discussed in relation to issues of clinical practice and research design in neuropsychological assessment.

Adult↗
PubMed2005

Action (verb) fluency: test-retest reliability, normative standards, and construct validity.

Action (verb) fluency is a newly developed verbal fluency task that requires the examinee to rapidly generate as many verbs (i.e., "things that people do") as possible within 1 min. Existing literature indicates that action fluency may be more sensitive to frontal-basal ganglia loop pathophysiology than traditional noun fluency tasks (e.g., animal fluency), which is consistent with the hypothesized neural dissociation between noun and verb retrieval. In the current study, a series of analyses were undertaken to examine the psychometric properties of action fluency in a sample of 174 younger healthy participants. The first set of analyses describes the development of demographically adjusted normative data for action fluency. Next, a group of hypothesis-driven correlational analyses reveals significant associations between action fluency and putative tests of executive functions, verbal working memory, verbal fluency, and information processing speed, but not between action fluency and tests of learning or constructional praxis. The final set of analyses demonstrates the test-retest stability of the action fluency test and provides standards for determining statistically reliable changes in performance. In sum, this study enhances the potential clinical applicability of action fluency by providing demographically adjusted normative data and demonstrating evidence for its reliability and construct validity.

Adolescent↗
PubMed2004

Action (verb) generation in HIV-1 infection.

It has been proposed that verb generation is primarily associated with left fronto-basal ganglia circuits, whereas the generation of nouns is principally mediated by dominant left temporo-parietal networks. Consistent with this premise, action (verb) fluency - a verbal fluency task requiring the spontaneous generation of verbs - has shown greater sensitivity to frontal-basal ganglia pathophysiology (e.g., dementia in Parkinson's disease (PDD)) than noun fluency. The present study examined action and noun fluency in persons with HIV-1 infection-a disease known to be associated with a frontal-basal ganglia circuit neuropathogenesis. Action and noun ("animals") verbal fluency protocols were administered to 97 persons with HIV-1 infection and 20 demographically comparable healthy comparison (HC) subjects. A significant interaction emerged between verbal fluency task and HIV-1 serostatus such that the HIV+ group generated significantly fewer actions (verbs) relative to the HC sample. Findings indicate that persons infected with HIV-1 experience difficulty rapidly generating verbs, but not nouns from semantic memory. Considering the prominent frontal-basal ganglia circuit neuropathophysiology of HIV-1 infection, these data are consistent with the hypothesized dissociation between noun and verb generation as pertains to generative fluency.

Adult↗
PubMed2004

Neurocognitive performance of methamphetamine users discordant for history of marijuana exposure.

Abuse of the stimulant drug methamphetamine is associated with neural injury and neuropsychological (NP) deficits, while the residual effects of marijuana use remain uncertain. We sought to determine if methamphetamine dependent persons who also met criteria for marijuana abuse or dependence evidenced different NP performance than those with dependence for methamphetamine alone. We examined three groups that did not differ significantly on important demographic factors: (1) subjects with a history of methamphetamine dependence and history of marijuana abuse/dependence (METH+/MJ+, n=27); (2) methamphetamine dependent subjects without history of marijuana abuse/dependence (METH+/MJ-, n=26); (3) a control group with minimal or no drug use (n=41). A comprehensive NP battery was administered and performance was quantified for five cognitive ability areas. The METH+/MJ- group generally demonstrated the greatest NP impairment, with statistically significant differences observed between the METH+/MJ- and control group in learning, retention/retrieval, and a summary score of global NP performance. The METH+/MJ+ group did not differ significantly from the control or METH+/MJ- group on any NP ability. However, there was a significant linear trend in the global NP score suggesting that the METH+/MJ+ performed intermediate to the control and METH+/MJ- groups. Based on these findings, we cannot conclude that there is a protective effect of marijuana use in methamphetamine users; however, marijuana use clearly did not appear to exacerbate methamphetamine neurotoxicity. Further investigations are needed to determine if the emerging literature, suggesting that certain cannabinoids might have neuroprotective actions, is generalizable to community-dwelling substance abusers.

Adult↗
PubMed2004

A comparison of injection and non-injection methamphetamine-using HIV positive men who have sex with men.

There is a paucity of research on the psychosocial and behavioral characteristics of individuals who inject methamphetamine (meth). The present study compared injection and non-injection users of meth in terms of background characteristics, drug use patterns, health and social problems, sexual risk behavior, and psychosocial factors. The sample consisted of 194 HIV+Men who have Sex with Men (MSM) who were enrolled in a sexual risk reduction intervention for meth users. Men who injected meth were significantly more likely to be Caucasian, bisexual, homeless, divorced/separated, with lower educational attainment as compared to non-injectors. Injectors also reported more years of meth use, greater frequency and amount of meth use, more social and health problems, including higher prevalence of STDs and Hepatitis C, and more sexual risk behaviors. In terms of psychosocial factors, injection users of meth scored significantly higher on measures of impulsivity and experiences of rejection, and lower on a measure of emotional support. A multivariate logistic regression revealed that educational attainment and experiences of rejection were the factors that best discriminated between injection and non-injection users of meth. The unique characteristics of injection meth users are discussed in relation to the development of effective HIV prevention programs for the target population.

Adult↗
PubMed2004

Effects of depressive symptoms and anxiety on hemostatic responses to acute mental stress and recovery in the elderly.

Depression and anxiety are prospectively associated with cardiac morbidity and mortality. Increased clotting diathesis may mediate this link. We hypothesized that there would be an association between mood and hemostatic changes that occur during and following recovery from acute mental stress. Forty-eight community-dwelling elderly subjects underwent a laboratory speech stressor task. Plasma von Willebrand factor (vWF), thrombin/antithrombin III (TAT) complexes, D-dimer, tissue-type plasminogen activator (t-PA), and type I plasminogen activator inhibitor (PAI-1) were measured at rest, after conclusion of the speech, and 14 min afterwards (recovery). Mood was assessed with the Hamilton Rating Scales for Depression (Ham-D) and Anxiety (Ham-A). Mental stress elicited a hypercoagulable state as evidenced by increases in TAT and D-dimer, and by a decrease in t-PA. Overall, hypercoagulability had increased after recovery. Ham-D scores and Ham-A scores correlated with increases in D-dimer over the testing interval (i.e. area under the curve). Ham-A (but not Ham-D) uniquely explained 8% and 17% of the variance in resting D-dimer and D-dimer area under the curve, respectively. The independent association of anxiety symptoms with resting and stress-induced fibrin formation (D-dimer) may be a mechanism linking mood with cardiovascular disease risk in the elderly.

Acute Disease↗
PubMed2004

Effects of HIV-1 infection and aging on neurobehavioral functioning: preliminary findings.

OBJECTIVE: The effects of aging on the presentation of HIV-associated neurocognitive disorders are largely unknown. In a cross-sectional observational study, we compared the neuropsychological profiles of 67 HIV-positive patients aged at least 50 years with those of 52 participants aged 35 years or less. METHODS: Participants received neuropsychological, psychiatric and neuromedical evaluations. Raw neuropsychological test scores were converted to demographically corrected T-scores; all were corrected for the effects of normal aging. Clinical ratings of impairment were assigned to the neuropsychological results. RESULTS: The two groups did not differ statistically with respect to demographic variables, percentage with AIDS, or CD4 cell counts. The 'younger' group had higher viral burdens in plasma and cerebrospinal fluid (CSF), and fewer were receiving antiretroviral treatment. The proportion of neuropsychologically impaired subjects in the 'older' group was slightly greater than in the younger group, and the older group tended to have higher rates of impairment across most ability domains. When group differences in CSF viral load were modeled statistically, both viral burden and age were significant predictors of neuropsychological impairment, together with a significant interaction between viral burden and age. Older individuals with detectable virus in CSF had twice the prevalence of neuropsychological impairment of those with undetectable levels. Among younger individuals, this proportion was not affected by viral load. Lifetime major depression, substance use disorder, and current depression symptoms were not associated with neuropsychological impairment. CONCLUSION: Although further studies with larger and older samples are needed, this investigation suggests that older adults may be at greater risk of HIV-related neurocognitive dysfunction.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Correlation of in vivo neuroimaging abnormalities with postmortem human immunodeficiency virus encephalitis and dendritic loss.

BACKGROUND: In the absence of significant opportunistic infection, the most common alterations on neuroimaging in the brains of patients with AIDS include enlarged cerebrospinal fluid spaces, white-matter loss, volume loss in striatal structures, and white-matter signal abnormalities. Although previous studies have linked brain viral levels to these alterations, other neuropathological mechanisms might also contribute to them. OBJECTIVE: To examine the relationship between findings on premortem magnetic resonance images and postmortem neuropathologic evidence of human immunodeficiency virus (HIV) encephalitis and neurodegeneration. DESIGN: Morphometric analysis of magnetic resonance imaging in seropositive cases with matched seronegative controls, and the correlation of these volumes to neuropathological measures in autopsied seropositive cases. SETTING: University of California, San Diego, HIV Neurobehavioral Research Center. SUBJECTS: Twenty-one seropositive subjects studied at autopsy and 19 seronegative cases. MAIN OUTCOME MEASURES: In vivo structural magnetic resonance imaging data analyzed by quantitative methods, with comparison of volumes from magnetic resonance imaging and neuropathological data from autopsies. RESULTS: The HIV-seropositive subjects demonstrated cerebrospinal fluid increases relative to seronegative controls. These increases were associated with a significant decrease in the volumes of cerebral and cerebellar white matter, caudate nucleus, hippocampus, and, to a lesser extent, cerebral cortex. The volume of cerebral white-matter tissue with elevated signal was also increased. This signal elevation in white matter predicted the autopsy diagnosis of HIV encephalitis, as well as the extent of dendritic loss as assessed by analysis of microtubule-associated protein 2 immunoreactivity. CONCLUSIONS: White-matter and cortical damage resulting from HIV disease are closely related. In vivo magnetic resonance imaging may be a valuable adjunct in the assessment of patients at risk for developing HIV encephalitis.

Adult↗
PubMed2004

Enhancing antiretroviral therapy for human immunodeficiency virus cognitive disorders.

The benefits of combination antiretroviral therapy (ART) for HIV cognitive disorders vary substantially between individuals. This study evaluated whether cerebrospinal fluid (CSF) drug penetration and CSF virological suppression influence the extent of neuropsychological (NP) improvement during ART. Overall performance on a battery of NP tests administered at baseline and follow-up (median 15 weeks) was computed by using the global deficit score (GDS) methods in 31 cognitively impaired, HIV-infected individuals who began new ART regimens. Virological suppression (attaining undetectable viral load by RT-PCR at follow-up) was assessed separately for plasma and CSF. Subjects on regimens containing greater numbers of CSF-penetrating drugs showed significantly greater reduction in CSF viral load. Subjects attaining CSF virological suppression demonstrated greater GDS improvement than those who did not (median GDS change, 0.62 vs 0.23; p = 0.01). A similar trend for plasma did not reach statistical significance (p = 0.053). NP improvement was greater in ART-naive versus treatment-experienced subjects. In a multivariate model (overall p = 0.0008), significant, independent predictors of GDS reduction were CSF HIV RNA suppression, baseline antiretroviral history, and their interaction. Including CSF-penetrating drugs in the ART regimen and monitoring CSF viral load may be indicated for individuals with HIV-associated cognitive impairment.

Adult↗
PubMed2004

Determinants of condom use stage of change among heterosexually-identified methamphetamine users.

There is a paucity of research on the association between methamphetamine use (meth) and sexual risk behavior among heterosexual meth users. This study used a multiple theories approach to identify factors associated with stage of change for condom use in a sample of 181 HIV-negative, heterosexually identified meth users. Background characteristics, drug use variables, and theoretical mechanism of change variables were examined in relation to Prochaska's contemplative and preparation stages of change. Sexual risk behavior was highest among those in the contemplation stage of change. When compared with those in the preparation stage of change, contemplators were more likely to be never married, more likely to have an STD, consumed larger amounts of meth and other illicit drugs, had lower scores on self-efficacy and outcome expectancies for condom use and negotiation of safer sex practices, and had less positive social norms in relation to AIDS preventive behaviors. A multivariate logistic regression revealed that the preparation stage of change was associated with increased self-efficacy for condom use, stronger social norms regarding condom use, and reduced occurrence of sexually transmitted diseases. The findings are discussed in relation to the development of sexual risk reduction interventions for heterosexual meth users.

Adult↗
PubMed2004

The context of sexual risk behavior among heterosexual methamphetamine users.

Relatively little is known about the relationship between methamphetamine (meth) use and sexual risk behavior among heterosexual adults. This descriptive study explores the context of sexual risk behavior among HIV-negative, heterosexual meth-using men and women. Drug use history, motivations for meth use, relationship types, and the social-sexual context of meth use were examined as factors that relate to sexual risk behavior and meth use. The majority of participants were white males with an average age of 38.6 years. Primary motivations for current meth use were to get high, to get more energy, and to party. Participants used meth an average of 14 days per month and consumed an average of 7.9 g during this period. The average number of unprotected vaginal, anal, and oral sex acts over a 2-month period were 21.5, 6.3, and 41.7, respectively. Participants reported an average of 9.4 sex partners over 2 months. The findings are discussed in relation to HIV prevention messages and the development of sexual risk reduction interventions for HIV-negative, heterosexual meth users.

Adult↗
PubMed2004

CCR2 polymorphisms affect neuropsychological impairment in HIV-1-infected adults.

CCR2 is a minor coreceptor for human immune deficiency virus-1 (HIV-1) and its impact on HIV-1-related neuropsychological impairment (NPI) remains unknown. We studied the impact of CCR2-V64I polymorphisms on the development of NPI in 121 HIV-1 patients. The CCR2-64-I allele was associated with rate of progression to NPI when measured from the first study visit (Log Rank p=0.01) or from the estimated time of seroconversion (p=0.02). CCR2-V64I was not associated with plasma or CSF HIV-1 RNA load, suggesting that the impact of CCR2 on neuropathogenesis may involve alterations in inflammatory responses within the CNS rather than a direct impact on viral entry or replication.

Adult↗
PubMed2004

The monocyte chemotactic protein-1 -2578G allele is associated with elevated MCP-1 concentrations in cerebrospinal fluid.

Because monocyte chemotactic protein (MCP)-1 is an important cofactor in HIV neuropathogenesis, we investigated the relationship between MCP-1 genotype and expression in cerebrospinal fluid (CSF). We evaluated a genetic polymorphism in the MCP-1 promoter at position -2578 (alternatively designated -2518) in 98 HIV-infected subjects who had contemporaneously collected plasma and CSF. CSF MCP-1 levels were highest in the G/G genotype group, intermediate in the G/A group, and lowest in the A/A group. MCP-1 levels in plasma only differed by genotype after adjusting for HIV-related factors. Our findings suggest that this MCP-1 promoter polymorphism influences HIV neuropathogenesis by regulating MCP-1 protein expression in the central nervous system (CNS).

Adult↗
PubMed2004

Qualitative aspects of verbal fluency in HIV-associated dementia: a deficit in rule-guided lexical-semantic search processes?

HIV-associated dementia (HAD) is widely considered a "subcortical" dementia that involves a disruption of frontal-basal ganglia circuits. Deficits in verbal fluency are common in HAD; however, the cognitive underpinnings of these deficits are not well understood. To elucidate the cognitive mechanisms underlying the diminished verbal fluency output in HAD, we examined several qualitative aspects of letter fluency in 21 individuals with HAD, 51 nondemented persons with HIV infection (HIV+), and 30 healthy controls (HC) who were comparable for age, education, sex, ethnicity, and estimated premorbid verbal intelligence. The verbal fluency protocols were scored to obtain the total number of correct words, average phonemic cluster size, total number of switches between phonemic clusters, and the proportion of error responses (i.e., intrusions, perseverations, and variants). Consistent with prior research, HAD participants produced significantly fewer total correct words relative to the HC and nondemented HIV+ groups. The HAD group also demonstrated fewer switches and a higher proportion of response errors (especially intrusion errors), but no differences were observed in average cluster size. Findings are interpreted as reflecting a disruption of rule-guided lexical-semantic search strategies in HAD, perhaps mediated by prefrontal-striatal circuit dysfunction, rather than depleted lexical-semantic memory stores.

AIDS Dementia Complex↗