Eileen M. Martin

Vascular risk factors, HIV serostatus, and cognitive dysfunction in gay and bisexual men

Background: The purpose of this study was to evaluate the relationship between cognitive performance, risk factors for cardiovascular and cerebrovascular disease (CVD), and HIV infection in the era of highly active antiretroviral therapy. Methods: We evaluated the cognitive functions of men enrolled in the cardiovascular disease substudy of the Multicenter AIDS Cohort Study who were aged ≥40 years, with no self-reported history of heart disease or cerebrovascular disease. Results from comprehensive neuropsychological evaluations were used to construct composite scores of psychomotor speed and memory performance. Subclinical CVD was assessed by measuring coronary artery calcium and carotid artery intima-media thickness (IMT), as well as laboratory measures, including total cholesterol, fasting glucose, glycosylated hemoglobin, glomerular filtration rate (estimated), and standardized blood pressure and heart rate measures. Results: After accounting for education, depression, and race, carotid IMT and glomerular filtration rate were significantly associated with psychomotor speed, whereas IMT was associated with memory test performance. HIV serostatus was not significantly associated with poorer cognitive test performance. However, among the HIV-infected individuals, the presence of detectable HIV RNA in plasma was linked to lower memory performance. Conclusions: These findings suggest that HIV infection may not be the most important predictor of cognitive performance among older gay and bisexual men in the post–highly active antiretroviral therapy era, at least among those with access to medical care and to appropriate medications. Medical factors associated with normal aging are significantly associated with performance on neuropsychological tests, and good clinical management of these factors both in HIV-infected individuals and those at risk for infection may have beneficial effects in the short term and could reduce the risk of subsequent cognitive decline.

Neurocognitive effects of repetitive transcranial magnetic stimulation in severe major depression.

OBJECTIVE Repetitive transcranial magnetic stimulation (rTMS) is being investigated as a potential treatment for depression. Few studies have addressed the neurocognitive effects of a course of rTMS in severely depressed patients. We evaluated neurocognitive effects of a 1-4 week course (mean 3 weeks) of rTMS using an aggressive set of parameters, in 15 severely depressed subjects. METHODS A battery of neurocognitive tests relevant to attention, working memory-executive function, objective memory and motor speed were administered to 15 subjects with treatment-resistant major depression (unipolar and bipolar), before and after a course of rTMS. Mean z scores were computed for each of 4 cognitive domains and analyzed using repeated measures multivariate analysis of covariance. Significant interactions were further clarified using univariate analysis of variance. RESULTS There was no worsening of performance on any of the cognitive domains over the baseline-post rTMS period. On the contrary, evidence of modest but statistically significant improvement in performance was noted in working memory-executive function, objective memory and fine motor speed domains over the rTMS treatment period. CONCLUSIONS There was no evidence of adverse neurocognitive changes over the baseline-post rTMS period in 15 treatment-resistant depressed subjects undergoing a 3 week (mean) trial of rTMS. Significant improvements in several domains observed over the rTMS treatment period could not be explained by improved mood. Practice effects as well as other factors potentially contributing to these findings are discussed. SIGNIFICANCE rTMS is being increasingly studied as a neurophysiological probe as well as for its potential antidepressive effects. The effects on neuronal function raise appropriate questions of safety of its use at varying stimulus parameters and durations. This study contributes to the small body of evidence of the cognitive effects of rTMS in severely depressed patients.

Subcortical brain atrophy persists even in HAART-regulated HIV disease

The purpose of this study was to determine the pattern and extent of caudate nucleus and putamen atrophy in HIV-infected men with well-controlled immune status and viral replication. 155 men underwent structural brain magnetic resonance imaging; 84 were HIV-infected and 71 were uninfected controls. MRI data were processed using the Fully Deformable Segmentation routine, producing volumes for the right and left caudate nucleus and putamen, and 3-D maps of spatial patterns of thickness. There was significant atrophy in the HIV-infected men in both the caudate and putamen, principally in the anterior regions. The volume of the basal ganglia was inversely associated with the time since first seropositivity, suggesting that either there is a chronic, subclinical process that continues in spite of therapy, or that the extent of the initial insult caused the extent of atrophy.

Executive functions among individuals with methamphetamine or alcohol as drugs of choice: preliminary observations

Substance dependent individuals (SDIs) are frequently, but not invariably, impaired on tasks of executive functions. In this study, we examine patterns of executive performance among subjects with different self-reported “drug of choice” (defined as substance used >80% of the time prior to abstinence). Subjects were 33 abstinent SDIs receiving inpatient treatment and 19 non-SDI normal controls (NC) well-matched on age, sex, ethnicity, and VIQ, who were assessed using the Iowa Gambling Task (GT) and a delayed non-match to sample task (DNM): measures of decision making and working memory, respectively. Seventeen SDIs identified alcohol (AL group) and 16 SDIs identified methamphetamine (METH group) as their drug of choice. Overall, the METH group performed more poorly than the NC and AL groups on both tasks, with the largest differences observed in working memory. The AL group was not significantly impaired overall compared to NCs on either task, but showed subtle abnormalities of GT performance similar to the METH group. These preliminary findings suggest that self-reported drug of choice on admission to treatment may be associated with different patterns of executive performance during early recovery.

Impairments in memory and hippocampal function in HIV-positive vs HIV-negative women: a preliminary study.

Objective: Neurocognitive studies of HIV typically target executive functions dependent on frontostriatal circuitry. The integrity of medial temporal systems has received considerably less attention despite high hippocampal viral load. Studies also predominately involve HIV+ men, though HIV+ women may be at increased risk for cognitive dysfunction due to the high prevalence of psychosocial/mental health problems and lower educational attainment. Our aim was to conduct a preliminary investigation of episodic memory and its neural correlates in HIV-infected and at-risk uninfected women. Methods: Participants included 54 HIV+ and 12 HIV− women (mean age = 43 years; 86% African American) recruited from the Chicago site of the Womens Interagency HIV Study. Participants completed standardized tests of verbal and visual episodic memory, working memory, and executive function. A subset of 11 women also underwent functional MRI during a delayed verbal episodic memory task. Results: HIV serostatus predicted significantly lower immediate and delayed verbal episodic memory, working memory, and visual memory. Preliminary neuroimaging findings revealed group differences in bilateral hippocampal function, with HIV+ women showing decreased activation during encoding and increased activation during delayed recognition. These alterations correlated with worse episodic verbal memory. Conclusions: Verbal episodic memory deficits are evident in HIV+ women and may be associated with hippocampal dysfunction at both encoding and retrieval.

The influence of executive functions, sensation seeking, and HIV serostatus on the risky sexual practices of substance-dependent individuals

From a public health standpoint, identifying factors that contribute to risky sexual practices among substance-dependent individuals is critical, particularly in the context of HIV infection. This study examines the respective contributions of executive neurocognitive functions, sensation seeking, and HIV serostatus in predicting risky sexual practices among poly-substance users (with a history of dependence primarily for cocaine or cocaine/heroin). HIV+ (n=109) and HIV- (n=154) substance-dependent individuals were assessed using three neurocognitive tasks of executive functions: Stroop reaction time, delayed non-matching to sample, and the Iowa Gambling Task. Sensation seeking was assessed using the Sensation Seeking Scale-V. Greater sensation seeking was associated with more risky sexual practices among HIV+ participants, particularly among those who performed best on the Iowa Gambling Task. Our findings indicate that continued risk behavior among HIV+ drug users may be driven by sensation seeking (a personality trait common among drug users); however, the impact of executive functions is less clear.

Prevalence of HIV-associated neurocognitive disorders in the Multicenter AIDS Cohort Study

Objective: To evaluate the frequency of HIV-associated neurocognitive disorder (HAND) in HIV+ individuals and determine whether the frequency of HAND changed over 4 years of follow-up. Methods: The Multicenter AIDS Cohort Study (MACS) is a prospective study of gay/bisexual men. Beginning in 2007, all MACS participants received a full neuropsychological test battery and functional assessments every 2 years to allow for HAND classification. Results: The frequency of HAND for the 364 HIV+ individuals seen in 2007–2008 was 33% and for the 197 HIV+ individuals seen at all time periods during the 2007–2008, 2009–2010, and 2011–2012 periods were 25%, 25%, and 31%, respectively. The overall frequency of HAND increased from 2009–2010 to 2011–2012 (p = 0.048). Over the 4-year study, 77% of the 197 HIV+ individuals remained at their same stage, with 13% showing deterioration and 10% showing improvement in HAND stage. Hypercholesterolemia was associated with HAND progression. A diagnosis of asymptomatic neurocognitive impairment was associated with a 2-fold increased risk of symptomatic HAND compared to a diagnosis of normal cognition. Conclusion: HAND remains common in HIV+ individuals. However, for the majority of HIV+ individuals on combination antiretroviral therapy with systemic virologic suppression, the diagnosis of HAND is not a progressive condition over 4 years of follow-up. Future studies should evaluate longitudinal changes in HAND and specific neurocognitive domains over a longer time period.

The relationship between positive symptoms and instrumental work functioning in schizophrenia: a 10 year follow-up study.

This longitudinal investigation was designed to determine the association between the positive symptoms of psychosis and instrumental work functioning among patients with schizophrenia in comparison to patients with affective disorders. 173 participants were assessed prospectively for the presence of psychosis and concurrent work adjustment using a series of standardized measures at four consecutive follow-ups over a 10 yr period. The data demonstrate a significant relationship between psychosis and increased impairment in work functioning across diagnostic groups for three of the four follow-up periods (p<0.01), with this relationship being most consistent for the schizophrenia patients throughout the course of their disorder (p<0.01). The more severely psychotic patients, regardless of diagnosis, are least likely to be working effectively; however, the debilitating effect of psychosis on work adjustment is most evident for schizophrenia patients.

Performance of young adult cannabis users on neurocognitive measures of impulsive behavior and their relationship to symptoms of cannabis use disorders

Recent studies suggest that abstinent cannabis users show deficits on neurocognitive laboratory tasks of impulsive behavior. But results are mixed, and less is known on the performance of non-treatment-seeking, young adult cannabis users. Importantly, relationships between performance on measures of impulsive behavior and symptoms of cannabis addiction remain relatively unexplored. We compared young adult current cannabis users (CU, n = 65) and nonusing controls (NU, n = 65) on several laboratory measures of impulsive behavior, as well as on a measure of episodic memory commonly impacted by cannabis use. The CU group performed more poorly than the NU group on the Hopkins Verbal Learning Test–Revised Total Immediate Recall and Delayed Recall. No significant differences were observed on the measures of impulsive behavior (i.e., Iowa Gambling Task, IGT; Go–Stop Task; Monetary Choice Questionnaire; Balloon Analogue Risk Task). We examined relationships between neurocognitive performance and symptoms of cannabis use disorder symptoms (Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition, DSM–IV CUD) among the CU group, which revealed that poorer IGT performance was associated with more symptoms of DSM–IV CUD. Our results show poorer memory performance among young adult cannabis users than among healthy controls, but no differences on measures of impulsive behavior. However, performance on a specific type of impulsive behavior (i.e., poorer decision making) was associated with more cannabis use disorder symptoms. These results provide preliminary evidence to suggest that decision-making deficits may be more strongly associated with problems experienced from cannabis use, rather than solely being a consequence of cannabis use, per se. This publication was supported by Grants K23DA023560 and R01DA031176 (PI: Gonzalez) and F31DA032244 (PI: Schuster) from the National Institute on Drug Abuse (NIDA), as well as P01 CA098262 (PI: Mermelstein) from the National Cancer Institute (NCI). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

Characteristics of prospective memory deficits in HIV-seropositive substance-dependent individuals: preliminary observations.

The construct of “prospective memory” (PM) refers to a type of episodic memory for a future intention or “remembering what one must do.” This function has been proposed as a candidate mechanism underlying behaviors of critical importance in HIV disease, including adherence with medication regimens and continued engagement in risk behavior. We administered tasks of time-based and event-based prospective memory and control tasks of retrospective and working memory to 31 HIV-seropositive and 35 HIV-seronegative substance-dependent individuals (SDIs). We found that compared with HIV− controls HIV+ participants showed deficits in time-based but not event-based PM. Retrospective, but not working, memory performance correlated significantly with time-based PM performance. In addition, performance on the time-based PM task was a significant predictor of scores on a self-report measure of risky sexual and injection practices. These preliminary data provide new and unique findings regarding the components of executive function mediated by prefrontal cortical systems that are impaired among HIV+ SDIs and their relevance to “real-world” behaviors.