Incidental Learning and Memory Deficits on a Computerized Symbol-Digit Modalities Test in Adults with HIV/AIDS.

OBJECTIVE: Incidental learning and memory, as well as processing speed, were examined in human immunodeficiency virus (HIV)-positive adults and a seronegative control group. METHODS: Participants completed a computerized Symbol-Digit Modalities Test (cSDMT) with two blocked conditions: a set of trials with the standard symbol-digit pairings and the second set with a rearranged symbol-digit pairings. RESULTS: HIV-positive adults showed slower overall reaction time compared to the HIV-negative group. More importantly, the most cognitively impaired HIV-positive group showed no interference in the rearranged set of symbol-digit pairings from the standard pairings on the cSDMT. CONCLUSION: The relative slowing, or interference, in the HIV-negative group and two HIV-positive groups (unimpaired and impaired) was quite large (between 122 and 131 ms). We argue that the lack of such relative slowing in the most cognitively impaired HIV-positive group indicates a deficit in incidental learning and memory.

The cognitive effects of endocrine therapy in survivors of breast cancer: A prospective longitudinal study up to 6 years after treatment.

BACKGROUND: After treatment of primary breast cancer, endocrine therapy (ET) is prescribed for patients with hormone receptor-positive cancers. Despite ET recommendations of 5 to 10 years of treatment, to the authors' knowledge there is little prospective study of its impact on cognitive function over an extended period of time. ET has known pharmacologic effects on the brain. Cognitive side effects are a concern for many women, with mixed findings reported in various studies. The current prospective longitudinal study examined the neuropsychological effects of ET over time, up to 6 years after treatment. METHODS: A total of 189 survivors of early-stage breast cancer enrolled in the study prior to initiating ET if prescribed, and were followed at 6 months (175 patients), 12 months (173 patients), and for 3 to 6 years (102 patients) with self-report and neuropsychological assessments. Using linear mixed models, the authors examined whether neuropsychological performance or impairment rates differed over time based on whether or not ET was received. RESULTS: The authors did not find any effect of ET on neuropsychological performance or impairment at any time point among survivors who received it compared with women who did not. However, those who participated in the 3-year to 6-year year visit demonstrated better executive function at baseline. CONCLUSIONS: In the current observational cohort study, no detrimental effect of ET on cognitive function was identified in survivors of early-stage breast cancer receiving treatment with ET compared with those who were not.

Improvements in brain and behavior following eradication of hepatitis C.

Despite recent advances in treatment, hepatitis C remains a significant public health problem. The hepatitis C virus (HCV) is known to infiltrate the brain, yet findings from studies on associated neurocognitive and neuropathological changes are mixed. Furthermore, it remains unclear if HCV eradication improves HCV-associated neurological compromise. This study examined the longitudinal relationship between neurocognitive and neurophysiologic markers among healthy HCV- controls and HCV+ adults following successful HCV eradication. We hypothesized that neurocognitive outcomes following treatment would be related to both improved cognition and white matter integrity. Participants included 57 HCV+ participants who successfully cleared the virus at the end of treatment (sustained virologic responders [SVRs]) and 22 HCV- controls. Participants underwent neuropsychological testing and, for a nested subset of participants, neuroimaging (diffusion tensor imaging) at baseline and 12 weeks following completion of HCV therapy. Contrary to expectation, group-level longitudinal analyses did not reveal significant improvement in neurocognitive performance in the SVRs compared to the control group. However, a subgroup of SVRs demonstrated a significant improvement in cognition relative to controls, which was related to improved white matter integrity. Indeed, neuroimaging data revealed beneficial effects associated with clearing the virus, particularly in the posterior corona radiata and the superior longitudinal fasciculus. Findings suggest that a subgroup of HCV+ patients experienced improvements in cognitive functioning following eradication of HCV, which appears related to positive changes in white matter integrity. Future research should examine whether any additional improvements in neurocognition and white matter integrity among SVRs occur with longer follow-up periods.

Medication Adherence in HIV-Positive African Americans: The Roles of Age, Health Beliefs, and Sensation Seeking.

We examined how two critical constructs, health beliefs and sensation seeking, influence combination antiretroviral therapy adherence in HIV+ African Americans, and whether these factors mediate the association between age and adherence. Two-hundred-and-eighty-six HIV+ African Americans participated in this observational study. Path analyses revealed that higher levels of a specific health belief, perceived utility of treatment, and lower levels of a sensation-seeking component, Thrill and Adventure Seeking, directly predicted optimal adherence. The influence of age on adherence was partially mediated by lower Thrill and Adventure Seeking levels. Depression predicted adherence via perceived utility of treatment and Thrill and Adventure Seeking, whereas current substance abuse and dependence did via Thrill and Adventure Seeking. Poorer neurocognitive function had a direct, adverse effect on adherence. Our findings suggest that supporting the development of more positive perceptions about HIV treatment utility may help increase medication adherence among African Americans. This may be particularly relevant for those with higher levels of depression symptoms, which was directly associated with negative perceptions about treatment. Additionally, clinicians can assess sensation-seeking tendencies to help identify HIV+ African Americans at risk for suboptimal adherence. Compensatory strategies for medication management may help improve adherence among HIV+ individuals with poorer neurocognitive function.

Psychosocial Correlates of Medication Adherence among HIV-Positive, Cognitively Impaired Individuals.

Although cognitive impairment has been shown to adversely affect antiviral medication adherence, a subset of cognitively impaired adults nonetheless are able to adequately adhere to their medication regimen. However, little is known about factors that serve as buffers against suboptimal adherence among the cognitively impaired. This study consisted of 160 HIV-positive, cognitively impaired adults (Global Deficit Score ≥ 0.50) whose medication adherence was monitored over 6-months using an electronic monitoring device (MEMS caps). Logistic regressions were run to determine psychosocial variables associated with medication adherence. Higher self-efficacy and treatment related support, a stable medication regimen, stable stress levels, and absence of current stimulant use were predictive of optimal adherence. A distinct array of psychosocial factors was found that buffer against the adverse effects of cognitive impairment on medication adherence. Assessment and interventions targeting these factors may improve adherence rates among cognitively impaired adults.

Increased neurocognitive intra-individual variability is associated with declines in medication adherence in HIV-infected adults.

OBJECTIVE: There is cross-sectional evidence that neurocognitive intra-individual variability (IIV), or dispersion, is elevated in human immunodeficiency virus (HIV) disease and is associated with declines in activities of daily living, including medication adherence. METHODS: This longitudinal study extends this literature by examining whether increased neurocognitive IIV in HIV-positive persons over time predicts declines in medication adherence above and beyond changes in mean level of performance over a 6-month observation. RESULTS: After controlling for drug use, declines in mean performance, and changes in depressive symptoms, results confirmed that increases in IIV were associated with overall poorer antiretroviral medication adherence. HIV-positive individuals with the greatest increases in dispersion demonstrated marked reductions in adherence by the third month that exceeded what was observed in less variable individuals. CONCLUSIONS: Our results indicate that increases in dispersion are associated with poorer declines in medication adherence in HIV disease, which may have implications for the early detection and remediation of suboptimal antiretroviral adherence.

Interactive effects of neurocognitive impairment and substance use on antiretroviral non-adherence in HIV disease.

While numerous studies have established the adverse independent effects of clinical conditions including neurocognitive dysfunction, psychiatric illness, and substance abuse/dependence on medication adherence among HIV-infected adults, fewer have studied their interactive effects. The current study examined this issue among 204 HIV-infected participants based upon current neurocognitive functioning and DSM-IV-diagnosed psychiatric illness and current substance abuse or dependence. Results confirmed that participants with any of these risk factors demonstrated poorer adherence than individuals with no risk factors. A neurocognitive status × substance abuse/dependence interaction was also identified such that participants with impaired neurocognition and a co-occurring substance abuse/dependence diagnosis demonstrated the poorest adherence. Results confirm the deleterious impact of these risk factors in isolation and also identify a specific interactive effect for individuals with comorbid neurocognitive impairment and a substance abuse/dependence disorder. Findings highlight the need for interventions that simultaneously address these problems.

Neuroimaging abnormalities, neurocognitive function, and fatigue in patients with hepatitis C.

OBJECTIVE: This study examined neurologic abnormalities (as measured by proton magnetic resonance spectroscopy imaging and diffusion tensor imaging), neurocognitive performance, and fatigue among a sample of adults with hepatitis C virus (HCV). We hypothesized that HCV+ individuals would demonstrate structural brain abnormalities and neurocognitive compromise consistent with frontostriatal dysfunction as well as increased fatigue compared to controls. METHOD: Participants were 76 individuals diagnosed with HCV and 20 controls who underwent a comprehensive neurocognitive evaluation and clinical assessments. A subset of the HCV+ participants (n = 29) and all controls underwent MRI. RESULTS: Individuals diagnosed with chronic HCV infection demonstrated greater fractional anisotropy in the striatum as well as greater mean diffusivity in the fronto-occiptal fasciculus and external capsule compared to HCV- controls. HCV+ participants also demonstrated lower levels of N-acetylaspartate in bilateral parietal white matter and elevations in myo-inosital (mI) in bilateral frontal white matter compared to HCV- controls (all p values < 0.05). HCV+ participants also demonstrated significantly poorer neuropsychological performance, particularly in processing speed and verbal fluency. HCV+ patients reported higher levels of fatigue than controls, and fatigue was significantly correlated with diffusivity in the superior fronto-occipital fasciculus, elevations in mI in frontal white matter, and overall cognitive performance. CONCLUSIONS: Our results suggest that HCV-associated neurologic complications disrupt frontostriatal structures, which may result in increased fatigue and poorer cognitive performance, particularly in those cognitive domains regulated by frontostriatal regions.

Cognitive function after the initiation of adjuvant endocrine therapy in early-stage breast cancer: an observational cohort study.

PURPOSE: This report examines cognitive complaints and neuropsychological (NP) testing outcomes in patients with early-stage breast cancer after the initiation of endocrine therapy (ET) to determine whether this therapy plays any role in post-treatment cognitive complaints. PATIENTS AND METHODS: One hundred seventy-three participants from the Mind Body Study (MBS) observational cohort provided data from self-report questionnaires and NP testing obtained at enrollment (T1, before initiation of ET), and 6 months later (T2). Bivariate analyses compared demographic and treatment variables, cognitive complaints, depressive symptoms, quality of life, and NP functioning between those who received ET versus not. Multivariable linear regression models examined predictors of cognitive complaints at T2, including selected demographic variables, depressive symptoms, ET use, and other medical variables, along with NP domains that were identified in bivariate analyses. RESULTS: Seventy percent of the 173 MBS participants initiated ET, evenly distributed between tamoxifen or aromatase inhibitors. ET-treated participants reported significantly increased language and communication (LC) cognitive complaints at T2 (P = .003), but no significant differences in NP test performance. Multivariable regression on LC at T2 found higher LC complaints significantly associated with T1 LC score (P < .001), ET at T2 (P = .004), interaction between ET and past hormone therapy (HT) (P < .001), and diminished improvement in NP psychomotor function (P = .05). Depressive symptoms were not significant (P = .10). CONCLUSION: Higher LC complaints are significantly associated with ET 6 months after starting treatment and reflect diminished improvements in some NP tests. Past HT is a significant predictor of higher LC complaints after initiation of ET.

The impact of neurobehavioral features on medication adherence in HIV: evidence from longitudinal models.

Effective antiretroviral therapy has led to substantial improvements in health-related outcomes among individuals with HIV. Despite advances in HIV pharmacotherapy, suboptimal medication adherence remains a significant barrier to successful treatment. Although several factors have been associated with medication adherence in the extant literature, study assessing the effects of some of the neurobehavioral features specific to HIV has been limited. Moreover, although there is a growing body of literature measuring medication adherence in HIV prospectively, few employ advanced statistical methodologies suited to handle advanced models with multiple predictors that would strengthen our understanding of medication adherence trajectories in HIV. This study sought to integrate traditionally assessed predictors of medication adherence with neurobehavioral features of HIV in a longitudinal study of medication adherence to combined antiretroviral therapy (cART). The current study used multilevel modeling to examine a wide arrangement of categories of factors - demographic, medication related, psychosocial, and neurobehavioral - on medication adherence. The sample consisted of 235 HIV+ individuals whose medication adherence was monitored over the course of six months using electronic monitoring devices. After controlling for the effects of demographic, medication, and psychosocial factors, neurobehavioral features added predictive validity to the model. In the final model, simultaneously controlling for the effects of each of the predictors within all the categories, age, self-efficacy, executive functioning, apathy, and frequency of stimulant use emerged as unique individual predictors of average medication adherence across the 6-month study. Self-efficacy and irritability predicted changes in medication adherence over time. Adherence behavior is multidetermined. Adequate assessment of these factors, combined with timely intervention, appears to be warranted in order to boost adherence rates.

Assessment of the feasibility of a rehabilitation intervention program for breast cancer survivors with cognitive complaints.

To assess the feasibility of a cognitive rehabilitation program in breast cancer survivors (BCS) with persistent post-treatment cognitive complaints. BCS with cognitive complaints, 18-months to 5-years post-treatment, were recruited for a once-weekly, five-week, group cognitive training intervention. Outcome measures included self-reported mood and cognitive function, and neurocognitive tests administered at pre-intervention, immediate-, two-month and four-month post-intervention. A sub-study in eight participants evaluated resting state quantitative electroencephalography (qEEG) changes from pre- to immediate post-intervention in relationship to post-intervention changes in cognitive complaints. Twenty-seven BCS completed the protocol and tolerated the intervention well. We observed significant reductions in total and memory-specific cognitive complaints from pre-intervention to immediate post-intervention (p = 0.031 and p = 0.009, respectively) and at four-months post-intervention (p < 0.0001 and p < 0.001, respectively). Significant improvement in neurocognitive tests were found for Symbol Digit, Stroop, and Trails A tests (df = 26, all p's <0.05). Effect sizes for changes from pre-intervention to immediate and to four-month post intervention ranged from 0.429 to 0.607, and from 0.439 to 0.741, respectively. Increase in qEEG absolute alpha power over the course of the intervention was associated with reduced complaints at immediate post-intervention (r = -0.78, p = 0.021), two-months (r range = -0.76 to -0.82, p-value range 0.004 to 0.03), and four-months (r = -0.71, p = 0.048). A five-week group cognitive training intervention is feasible and well tolerated. Cognitive complaints and neurocognitive test performances showed positive changes. qEEG may serve as a potential biomarker for improvement in self-reported complaints. A randomized clinical trial is underway to test the efficacy of the intervention.

Cognitive complaints after breast cancer treatments: examining the relationship with neuropsychological test performance.

BACKGROUND: Cognitive complaints are reported frequently after breast cancer treatments. Their association with neuropsychological (NP) test performance is not well-established. METHODS: Early-stage, posttreatment breast cancer patients were enrolled in a prospective, longitudinal, cohort study prior to starting endocrine therapy. Evaluation included an NP test battery and self-report questionnaires assessing symptoms, including cognitive complaints. Multivariable regression models assessed associations among cognitive complaints, mood, treatment exposures, and NP test performance. RESULTS: One hundred eighty-nine breast cancer patients, aged 21-65 years, completed the evaluation; 23.3% endorsed higher memory complaints and 19.0% reported higher executive function complaints (>1 SD above the mean for healthy control sample). Regression modeling demonstrated a statistically significant association of higher memory complaints with combined chemotherapy and radiation treatments (P = .01), poorer NP verbal memory performance (P = .02), and higher depressive symptoms (P < .001), controlling for age and IQ. For executive functioning complaints, multivariable modeling controlling for age, IQ, and other confounds demonstrated statistically significant associations with better NP visual memory performance (P = .03) and higher depressive symptoms (P < .001), whereas combined chemotherapy and radiation treatment (P = .05) approached statistical significance. CONCLUSIONS: About one in five post-adjuvant treatment breast cancer patients had elevated memory and/or executive function complaints that were statistically significantly associated with domain-specific NP test performances and depressive symptoms; combined chemotherapy and radiation treatment was also statistically significantly associated with memory complaints. These results and other emerging studies suggest that subjective cognitive complaints in part reflect objective NP performance, although their etiology and biology appear to be multifactorial, motivating further transdisciplinary research.

Correlates of functional status among OEF/OIF veterans with a history of traumatic brain injury.

This study was conducted to identify factors related to functional status within a clinical sample of Veterans of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) with a history of traumatic brain injury (TBI). Medical chart review was conducted for a consecutive group of OEF/OIF Veterans who were referred for neuropsychological evaluation within a Veterans Affairs Medical Center Polytrauma Program related to history of TBI (n = 57). Level of involvement in occupational and academic activity, presence or absence of housing insecurity, and clinician ratings of overall functioning served as indicators of functional status. Reduced functional status was most strongly related to poorer cognitive function, particularly motor function, processing speed, and executive function. Lower levels of functioning were also related to increased severity of postconcussive symptoms, lower levels of education, and ongoing medication treatment for sleep or psychiatric symptoms. Comprehensive evaluation of cognitive, affective, and behavioral functioning among OEF/OIF Veterans with a history of TBI is likely to provide valuable information to inform rehabilitation strategies and identify potential warning signs for poor postdeployment reintegration. Increased awareness of these factors may aid clinicians in identifying patients at risk for poor outcomes and in more effectively targeting symptoms for intervention.

The role of HIV infection, cognition, and depression in risky decision-making.

The authors examined the impact of HIV, cognitive dysfunction, and depression on decision-making. HIV+ (N=100) and HIV- (N=26) participants were administered a comprehensive neuropsychological battery, a modified version of the Iowa Gambling Task, and a measure of depressive symptoms. HIV+ participants demonstrated more difficulties in learning the gambling task than did HIV- participants. Executive functioning and depression emerged as strong predictors of gambling task performance. Depression partially mediated the relationship between executive functioning and gambling performance. Our findings suggest that HIV infection, executive dysfunction, and depression place individuals at risk for poor decision-making.

2D MR Spectroscopy Combined with Prior-Knowledge Fitting Is Sensitive to HCV-Associated Cerebral Metabolic Abnormalities.

There is an evidence of neurocognitive dysfunction even in the absence of advanced liver disease in chronic hepatitis C virus (HCV) infection. Brain metabolism has been investigated non-invasively using one-dimensional (1D) in vivo Magnetic Resonance Spectroscopy (MRS) over three decades. Even though highly concentrated cerebral metabolites (N-acetylaspartate, creatine, choline, glutamate/glutamine, myo-inositol) have been detected using MRS, other metabolites at low concentrations (~1-3 mM or less) including glutathione, aspartate and GABA are quite difficult to observe using 1D MRS. In order to resolve overlapping resonances from a number of metabolites, a remedy is to add a second spectral dimension to the existing 1D MRS. Localized two-dimensional correlated spectroscopy (L-COSY) has been developed over the last decade to enhance the spectral dispersion by using the second spectral dimension. We have evaluated this L-COSY technique in the frontal white/gray matter regions of 14 HCV+ (mean age of 56.2 years) and 14 HCV- (mean age of 46.6 years) subjects. Our preliminary results showed significantly increased myo-inositol and glutathione in the HCV+ compared to the HCV- subjects. Hence, glutathione and myo-inositol should be considered along with other metabolites as important markers of inflammation.

Cognitive reserve as a protective factor in older HIV-positive patients at risk for cognitive decline.

The present study examined the impact of cognitive reserve in maintaining intact neuropsychological (NP) function among older HIV-positive individuals, a uniquely at-risk subgroup. Participants included 129 individuals classified by HIV serostatus, age group, and NP impairment. A three-way analysis of variance (ANOVA) followed by a series of within-group ANOVA and multiple regression analyses were conducted to investigate the pattern of cognitive reserve (vs. other protective) influence among groups with varying risks of NP impairment. Results indicated a significant age × HIV status interaction, with older HIV-positive individuals demonstrating higher cognitive reserve than subgroups with less risk for NP compromise (younger age and/or HIV-negative). Results demonstrated higher cognitive reserve specific to NP-intact older HIV-positive individuals. Within this group, the interaction of younger age and higher cognitive reserve independently contributed to cognitive status when controlling for psychiatric, immunological, and psychosocial protective mechanisms, suggesting the importance of cognitive reserve beyond other protective mechanisms in maintaining optimal NP functioning in those individuals most at risk. Alongside younger age, factors contributing to cognitive reserve (i.e., education and estimated premorbid intelligence) may provide substantial benefit for older HIV-positive adults who are at high risk for NP compromise.

Longitudinal change in cognitive function and medication adherence in HIV-infected adults.

Neuropsychological (NP) dysfunction has been linked to poor medication adherence among HIV-infected adults. However, there is a dearth of research examining longitudinal changes in the relationship between NP status and adherence rates. We hypothesized that declines in NP functioning would be associated with a corresponding decline in medication adherence while stable NP functioning would be associated with stable or improving adherence rates. Participants included 215 HIV-infected adults who underwent cognitive testing at study entry and six months later. Compared to the NP stable group, the NP decline group showed a greater drop in adherence rates. Further analysis revealed that, beyond global NP, learning and memory was significantly associated with changes in adherence rates. These findings further support the link between cognitive functioning and medication adherence and illustrates the importance of documenting changes in cognitive abilities for identifying individuals at risk for poor adherence.

Depression, cognition, and self-appraisal of functional abilities in HIV: an examination of subjective appraisal versus objective performance.

Depression frequently co-occurs with HIV infection and can result in self-reported overestimates of cognitive deficits. Conversely, genuine cognitive dysfunction can lead to an under-appreciation of cognitive deficits. The degree to which depression and cognition influence self-report of capacity for instrumental activities of daily living (IADLs) requires further investigation. This study examined the effects of depression and cognitive deficits on self-appraisal of functional competence among 107 HIV-infected adults. As hypothesized, higher levels of depression were found among those who over-reported problems in medication management, driving, and cognition when compared to those who under-reported or provided accurate self-assessments. In contrast, genuine cognitive dysfunction was predictive of under-reporting of functional deficits. Together, these results suggest that over-reliance on self-reported functional status poses risk for error when diagnoses require documentation of both cognitive impairment and associated functional disability in everyday life.

Medication and finance management among HIV-infected adults: the impact of age and cognition.

This study examined the effects of aging and cognitive impairment on medication and finance management in an HIV sample. We observed main effects of age (older < younger) and neuropsychological impairment on functional task performance. Interactions between age and cognition demonstrated that older impaired individuals performed significantly more poorly than all other comparison groups. There were no relationships between laboratory performance and self-reported medication and finance management. The interaction of advancing age and cognitive impairment may confer significant functional limitations for HIV individuals that may be better detected by performance-based measures of functional abilities rather than patient self-report.

Reaction time variability in HIV-positive individuals.

Progression of HIV/AIDS is frequently associated with frontal/subcortical dysfunction and mean reaction time (RT) slowing. Beyond group means, within-subject variability of RT has been found to be particularly sensitive to frontal/subcortical dysfunction in other populations. However, the possible relevance of RT variability to HIV/AIDS patients remains unknown. This study evaluated the relationships between RT variability and indicators such as neurocognitive, behavioral, and immunological status. A total of 46 HIV-positive adults on antiretroviral medication regimens were included in this study. Overall performance of this sample was poorer than normative means on measures of RT latency, RT variability, and traditional neurocognitive domains. Results demonstrated that the measures of RT variability were associated with global cognition, medication adherence rates, and peak immunological dysfunction, above and beyond the effects of RT latency. These preliminary findings suggest that measures of RT variability may provide enhanced sensitivity to neurocognitive disease burden in HIV/AIDS relative to more traditional measures of mean RT or cognitive function.