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1.  Prospective Memory in HIV-associated Neurocognitive Disorders (HAND): The Neuropsychological Dynamics of Time Monitoring 
Strategic monitoring during a delay interval is theorized to be an essential feature of time-based prospective memory (TB PM), the cognitive architecture of which is thought to rely heavily on frontostriatal systems and executive functions. This hypothesis was examined in 55 individuals with HIV-associated neurocognitive disorders (HAND) and 108 seronegative comparison participants who were administered the Memory for Intentions Screening Test (MIST), during which time monitoring (clock checking) behavior was measured. Results revealed a significant interaction between HAND group and the frequency of clock checking, in which individuals with HAND monitored checked the clock significantly less often than the comparison group across the TB PM retention intervals of the MIST. Subsequent analyses in the HAND sample revealed that the frequency of clocking checking was positively related to overall TB performance, as well as to standard clinical measures of retrospective memory and verbal fluency. These findings add support to a growing body of research elucidating TB PM’s reliance on strategic monitoring processes dependent upon intact frontostriatal systems. HIV-associated TB strategic time monitoring deficits may manifest in poorer functioning outcomes, including medication non-adherence and dependence in activities of daily living. Future research is needed to further delineate the cognitive mechanisms underlying strategic time monitoring in order to advise rehabilitation strategies for reducing HAND related TB PM deficits.
doi:10.1080/13803395.2013.776010
PMCID: PMC3631446  PMID: 23465043
HIV/AIDS; Prospective memory; Executive functions; Time perception; AIDS dementia complex
2.  Cognitive Neurorehabilitation of HIV-associated Neurocognitive Disorders: A Qualitative Review and Call to Action 
Neuropsychology review  2013;23(1):81-98.
Despite significant advances in the virologic management of HIV infection over the last two decades, effective treatments for HIV-associated neurocognitive disorders (HAND) remain elusive. While pharmacological interventions have yielded some success in improving neurocognitive outcomes in HIV, there is a dearth of rigorous studies examining the efficacy of cognitive rehabilitation for remediating HIV-associated neurocognitive impairment. This qualitative review summarizes and critiques the emerging literature on cognitive and behavioral treatments for HAND, which provides many reasons for optimism, but also has major limitations that underscore the scope of the work that lies ahead. Considering the notable real-world consequences of HAND, the development, validation, and clinical deployment of cognitive neurorehabilitation interventions tailored to the needs of persons living with HIV infection is a priority for clinical neuroAIDS investigators. In describing potential future directions for this endeavor, particular attention was paid to the application of cognitive neuropsychological principles in developing theory-driven approaches to managing HAND, improving everyday functioning, and enhancing HIV health outcomes.
doi:10.1007/s11065-013-9225-6
PMCID: PMC3606924  PMID: 23417497
HIV; AIDS dementia complex; cognition; cognitive rehabilitation
3.  Substance Use is a Risk Factor for Neurocognitive Deficits and Neuropsychiatric Distress in Acute and Early HIV Infection 
Journal of neurovirology  2012;19(1):65-74.
The acute and early stages of HIV infection (AEH) are characterized by substantial viral replication, immune activation, and alterations in brain metabolism. However, little is known about the prevalence and predictors of neurocognitive deficits and neuropsychiatric disturbances during this period. The present study examined the impact of demographic, HIV disease, and substance use factors on HIV-associated neurocognitive impairment and self-reported neuropsychiatric distress among 46 antiretroviral-naïve adults with median duration of infection of 75 days, relative to sample a of 21 HIV seronegative (HIV-) adults with comparable demographics and risk factors. Participants were administered a brief neurocognitive battery that was adjusted for demographics and assessed executive functions, memory, psychomotor speed, and verbal fluency, as well as the Profile of Mood States (POMS), a self-report measure of neuropsychiatric distress. Odds ratios revealed that AEH participants were nearly four times more likely than their seronegative counterparts to experience neurocognitive impairment, particularly in the areas of learning and information processing speed. Similarly, AEH was associated with a nearly five-fold increase in the odds of neuropsychiatric distress, most notably in anxiety and depression. Within the AEH sample, HIV-associated neurocognitive impairment was associated with problematic methamphetamine use and higher plasma HIV RNA levels, whereas neuropsychiatric distress was solely associated with high-risk alcohol use. Extending prior neuroimaging findings, results from this study indicate that HIV-associated neurocognitive impairment and neuropsychiatric distress are highly prevalent during AEH and are associated with high-risk substance use.
doi:10.1007/s13365-012-0141-y
PMCID: PMC3568179  PMID: 23250704
HIV; substance abuse; viral load; neuropsychiatry; AIDS dementia complex
4.  Concurrent Classification Accuracy of the HIV Dementia Scale for HIV-associated Neurocognitive Disorders in the CHARTER Cohort 
Background
The HIV Dementia Scale (HDS) was developed to screen for HIV-associated Neurocognitive Disorders (HAND), but concerns have persisted regarding its substandard sensitivity. This study aimed to examine the classification accuracy of the HDS using raw and norm-based cutpoints, and to evaluate the contribution of the HDS subtests to predicting HAND.
Methods
1,580 HIV-infected participants from 6 U.S. sites completed the HDS, and a gold standard neuropsychological battery, on which 51% of participants were impaired. Results: Sensitivity and specificity to HAND using the standard raw HDS cutpoint were 24% and 92%, respectively. The raw HDS subtests of attention, recall, and psychomotor speed significantly contributed to classification of HAND, while visuomotor construction contributed the least. A modified raw cutpoint of 14 yielded sensitivity of 66% and specificity of 61%, with cross-validation. Using norms also significantly improved sensitivity to 69% with a concomitant reduction of specificity to 56%, while the positive predictive value declined from 75% to 62% and negative predictive value improved from 54% to 64%. The HDS showed similarly modest rates of sensitivity and specificity among subpopulations of individuals with minimal comorbidity and successful viral suppression.
Conclusions
Findings indicate that while the HDS is a statistically significant predictor of HAND, particularly when adjusted for demographic factors, its relatively low diagnostic classification accuracy continues to hinder its clinical utility. A raw cutpoint of 14 greatly improved the sensitivity of the previously established raw cutscore, but may be subject to ceiling effects, particularly on repeat assessments.
doi:10.1097/QAI.0b013e318278ffa4
PMCID: PMC3529802  PMID: 23111573
HIV; cognition; HIV-associated neurocognitive disorders; screening measures; HIV dementia scale
5.  Co-Morbidities in Persons Infected with HIV: Increased Burden with Older Age and Negative Effects on Health-Related Quality of Life 
AIDS Patient Care and STDs  2013;27(1):5-16.
Abstract
This study sought to determine the synergistic effects of age and HIV infection on medical co-morbidity burden, along with its clinical correlates and impact on health-related quality of life (HRQoL) across the lifespan in HIV. Participants included 262 individuals across four groups stratified by age (≤40 and ≥50 years) and HIV serostatus. Medical co-morbidity burden was assessed using a modified version of the Charlson Co-morbidity Index (CCI). Multiple regression accounting for potentially confounding demographic, psychiatric, and medical factors revealed an interaction between age and HIV infection on the CCI, with the highest medical co-morbidity burden in the older HIV+cohort. Nearly half of the older HIV+group had at least one major medical co-morbidity, with the most prevalent being diabetes (17.8%), syndromic neurocognitive impairment (15.4%), and malignancy (12.2%). Affective distress and detectable plasma viral load were significantly associated with the CCI in the younger and older HIV-infected groups, respectively. Greater co-morbidity burden was uniquely associated with lower physical HRQoL across the lifespan. These findings highlight the prevalence and clinical impact of co-morbidities in older HIV-infected adults and underscore the importance of early detection and treatment efforts that might enhance HIV disease outcomes.
doi:10.1089/apc.2012.0329
PMCID: PMC3545369  PMID: 23305257
6.  Aging, Prospective Memory, and Health-Related Quality of Life in HIV Infection 
AIDS and behavior  2012;16(8):2309-2318.
HIV infection and older age are each independently associated with lower health-related quality of life (HRQoL) and deficits in prospective memory (PM), which is a distinct aspect of cognition involving the ability to “remember to remember” to do something at a future occasion. The present study investigated associations between PM and HRQoL in 72 older (≥ 50 years) and 41 younger (≤ 40 years) HIV-infected adults. Self-reported PM complaints predicted HRQoL across the entire sample, but there was a significant interaction between performance-based PM and age group on HRQoL, such that lower time-based PM was associated with lower HRQoL only in the younger cohort. Within the younger group, time-based and self-reported PM significantly predicted mental HRQoL independent of other risk factors (e.g., depression). These findings suggest that PM plays a unique role in HRQoL outcomes among younger persons living with HIV infection and support the examination of other age-related factors (e.g., effective use of compensatory strategies) that may regulate the adverse impact of PM on everyday functioning.
doi:10.1007/s10461-011-0121-x
PMCID: PMC3352996  PMID: 22246512
AIDS Dementia Complex; Aging; Prospective memory; Quality of life; Functional status; Health status
7.  Planning Deficits in HIV-Associated Neurocognitive Disorders: Component Processes, Cognitive Correlates, and Implications for Everyday Functioning 
Executive dysfunction remains among the most prevalent cognitive domains impaired in persons with HIV-associated neurocognitive disorders (HAND). However, little is known specifically about the cognitive architecture or everyday functioning implications of planning, which is an aspect of executive functions involving the identification, organization, and completion of sequential behaviors toward the accomplishment of a goal. The current study examined these issues using the Tower of LondonDX in 53 individuals with HAND, 109 HIV-infected persons without HAND, and 82 seronegative participants. The HAND+ group performed significantly more poorly than HIV-infected individuals without HAND on number of correct moves, total moves, execution time, time violations, and rule violations. Within the HIV+ group as a whole, greater total move scores and rule violations were most strongly associated with executive dysfunction. Of clinical relevance, elevated total moves and rule violations were significant, independent predictors of self-reported declines in instrumental activities of daily living and unemployment status in HIV. These results suggest that planning accuracy, efficiency, and rule-bound control are impaired in HAND, and may meaningfully affect more cognitively complex aspects of everyday living.
doi:10.1080/13803395.2012.692772
PMCID: PMC3460068  PMID: 22731608
Planned behavior; executive functioning; employment status; activities of daily living; higher order processes
8.  Synergistic Effects of HIV Infection and Older Age on Daily Functioning 
Objective
To determine whether HIV infection and aging act synergistically to disrupt everyday functioning.
Design
Cross-sectional, factorial study of everyday functioning in the context of HIV serostatus and age (≤ 40 years vs ≥ 50 years).
Methods
103 HIV+ and 87 HIV− participants were administered several measures of everyday functioning, including self-report indices of health-related quality of life (HRQoL) and instrumental and basic activities of daily living (IADLs and BADLs), and objective measures of functioning including employment and Karnofsky Performance Scale (KPS) ratings.
Results
Significant interaction effects of HIV and aging were observed for IADL and BADL declines, as well as KPS ratings (ps<.05), independent of potentially confounding factors. Follow-up contrasts revealed significantly worse functioning in the older HIV+ group for all functional outcome measures relative to the other study groups (ps<.05). A significant interaction effect was also observed on the emotional functioning HRQoL subscale, and additive effects of both age and HIV were observed for the physical functioning and general health perceptions HRQoL subscales (ps<.05). Significant predictors of poorer functioning in the older HIV+ group included current major depressive disorder for all outcomes, and comorbid medical conditions, lower estimated premorbid functioning, neurocognitive impairment, and nadir CD4 count for selected outcomes.
Conclusion
Findings suggest that older age may exacerbate the adverse effects of HIV on daily functioning, which highlights the importance of evaluating and monitoring the functional status of older HIV-infected adults. Early detection of functional difficulties could facilitate delivery of compensatory strategies (e.g., cognitive remediation) or assistive services.
doi:10.1097/QAI.0b013e31826bfc53
PMCID: PMC3480962  PMID: 22878422
HIV; aging; assessment; daily functioning; health status; disability
9.  Relationship of Medication Management Test-Revised (MMT-R) Performance to Neuropsychological Functioning and Antiretroviral Adherence in Adults with HIV 
AIDS and behavior  2012;16(8):2286-2296.
While performance-based tests of everyday functioning offer promise in facilitating diagnosis and classification of HIV-associated neurocognitive disorders (HAND), there remains a dearth of well-validated instruments. In the present study, clinical correlates of performance on one such measure (i.e., Medication Management Test—Revised; MMT-R) were examined in 448 HIV+ adults who were prescribed antiretroviral therapy. Significant bivariate relationships were found between MMT-R scores and demographics (e.g., education), hepatitis C co-infection, estimated premorbid IQ, neuropsychological functioning, and practical work abilities. MMT-R scores were not related to HIV disease severity, psychiatric factors, or self-reported adherence among participants with a broad range of current health status. However, lower MMT-R scores were strongly and uniquely associated with poorer adherence among participants with CD4 T-cell counts <200. In multivariate analyses, MMT-R scores were predicted by practical work abilities, estimated premorbid functioning, attention/working memory, learning, and education. Findings provide overall mixed support for the construct validity of the MMT-R and are discussed in the context of their clinical and research implications for evaluation of HAND.
doi:10.1007/s10461-012-0237-7
PMCID: PMC3575112  PMID: 22722882
HIV; medication management; neuropsychological functioning; adherence; construct validity; instrumental activities of daily living
10.  Elevated Neurobehavioral Symptoms are Associated with Everyday Functioning Problems in Chronic Methamphetamine Users 
Chronic methamphetamine (MA) use is commonly associated with neural injury and neurocognitive deficits. We examined the nature and correlates of self-reported neurobehavioral symptoms (i.e., apathy, disinihibition, and executive dysfunction) in 73 individuals with histories of MA dependence (MA+) and 85 comparison participants with comparable demographics and risk histories. MA+ individuals endorsed significantly more severe neurobehavioral symptoms on the Frontal Systems Behavioral Scale (FrSBe), especially disinhibition and executive dysfunction. Elevations in neurobehavioral symptoms were independent of common comorbidities, including hepatitis C infection, Attention-Deficit/Hyperactivity Disorder, mood disorders, and other substance use factors. Notably, the severity of neurobehavioral symptoms were uniquely associated with self-reported decrements in instrumental activities of daily living in the MA dependent sample. Findings indicate that chronic MA users may experience elevated neurobehavioral symptoms of disinhibition and executive dysfunction, potentially increasing their risk of functional declines.
doi:10.1176/appi.neuropsych.11080192
PMCID: PMC3735421  PMID: 23037647
Methamphetamine; Substance abuse; Executive dysfunction; Behavioral disinhibition; Neuropsychological assessment; Activities of daily living
11.  Semantic Cueing Improves Category Verbal Fluency in Persons Living with HIV Infection 
HIV-associated neurocognitive disorders (HAND) remain highly prevalent in the era of cART, but there are no validated psychological interventions aimed at improving cognitive outcomes. This study sought to determine the potential benefit of semantic cueing on category fluency deficits, which are prevalent in HIV and impact daily functioning. Eighty-six HIV-infected individuals and 87 demographically matched seronegative participants were administered a standard (i.e., uncued) and a cued category fluency task. Results revealed significant improvements in cued versus uncued performance in HIV, particularly for persons with lower levels of education. The cueing benefit observed may inform rehabilitation efforts aimed at ameliorating HAND.
doi:10.1176/appi.neuropsych.11100301
PMCID: PMC3396423  PMID: 22772666
infectious disease; verbal fluency; semantic memory; cognitive rehabilitation; executive functions; cognitive neuropsychology
12.  Longer Ongoing Task Delay Intervals Exacerbate Prospective Memory Deficits in HIV-associated Neurocognitive Disorders (HAND) 
The delay interval between encoding a future intention and detection of the retrieval cue is an essential feature of prospective memory (PM). McDaniel and Einstein’s (2000) multi-process theory posits that greater demands are placed on strategic monitoring processes as the delay interval lengthens. This hypothesis was examined in HIV-associated neurocognitive disorders (HAND), which are associated with strategic dyscontrol of PM likely secondary to prefrontostriatal circuit pathology. Seventy-eight seronegative adults and 49 individuals with HAND comprised the study groups, which were comparable with regard to demographic, psychiatric, and substance use factors. As part of a comprehensive neuropsychological evaluation, participants were administered a well-validated PM measure that included short (2-minute) and long- (15-min) task delay interval scales that utilized a standardized word search as the ongoing task. Results revealed a significant interaction of group and delay interval, with significant effects of HAND on PM at long, but not short delay. The long delay PM effect in HAND was driven primarily by deficits in time-based PM and was most strongly associated with markers of executive dysfunction. In concordance with the multi-process theory, individuals with HAND were disproportionately vulnerable to PM deficits at longer ongoing task delay intervals, which appear to be driven by strategic dyscontrol of PM that is consistent with the preferential disruption of prefrontal systems in neuroAIDS. Difficulty with successfully completing PM tasks following a longer delay could manifest in real-world problems, such as medication nonadherence and unemployment, and characterizing this specific deficit may inform remediation strategies.
doi:10.1080/13803395.2012.654764
PMCID: PMC3311720  PMID: 22299658
Prospective memory; HIV/AIDS; episodic memory; executive functions; time perception; AIDS Dementia Complex
13.  Construct Validity of the Item-Specific Deficit Approach to the California Verbal Learning Test (2nd ed) in HIV Infection 
The Clinical Neuropsychologist  2012;26(2):288-304.
Impairment in list learning and recall is prevalent in HIV-infected individuals and is strongly predictive of everyday functioning outcomes. Consistent with its predominant frontostriatal pathology, the memory profile associated with HIV infection is best characterized as a mixed encoding/retrieval profile. The Item-Specific Deficit Approach (ISDA) was developed by Wright et al. (2009) to elicit indices of Encoding, Consolidation, and Retrieval from the well-validated California Verbal Learning Test (CVLT; Delis et al., 1987; 2000). The current study evaluated construct validity of the ISDA for the CVLT-II in 40 persons with HIV-associated neurocognitive disorders (HIV+/HAND+), 103 HIV-infected persons without HAND (HIV+/HAND−), and 43 seronegative comparison subjects (HIV−). Results provided mixed support for the construct validity of ISDA indices. HIV+/HAND+ individuals performed significantly more poorly than persons in the HIV+/HAND− and HIV− groups on ISDA Encoding, Consolidation, and Retrieval deficit indices, which demonstrated adequate classification accuracy for diagnosing HIV+/HAND+ participants and evidence of both convergent (e.g., episodic memory) and divergent (e.g., motor skills) correlations in the HIV+/HAND+ participants. However, highly intercorrelated ISDA indices and traditional CVLT-II measures showed comparable between-groups effect sizes, classification accuracy, and correlations to other memory tests, thereby raising uncertainties about the incremental value of the ISDA approach in clinical neuroAIDS research.
doi:10.1080/13854046.2011.653404
PMCID: PMC3310968  PMID: 22394206
Human immunodeficiency virus; episodic memory; neuropsychological assessment; encoding; consolidation; retrieval
14.  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.
doi:10.1080/13803390590949494
PMCID: PMC1853378  PMID: 16676475
15.  Memory for Intentions is Uniquely Associated with Instrumental Activities of Daily Living in Healthy Older Adults 
Moderate declines in prospective memory (PM) are common among older adults, but whether such decrements are associated with everyday functioning problems is not well established. To examine this issue, we administered the Memory for Intentions Screening Test (MIST), Prospective and Retrospective Memory Questionnaire (PRMQ), and Activities of Daily Living Questionnaire (ADLQ) to 50 healthy older Australian adults as part of a broader neuropsychological battery. In a series of hierarchical regressions controlling for demographics, medical/psychiatric factors, and other neurocognitive functions, the MIST event-based PM score and PRMQ PM scale were significantly associated with the total number of instrumental ADL (IADL) domains in which participants reported needing assistance. Extending prior findings in clinical populations, results indicate that lower PM functioning is uniquely associated with mild, concurrent IADL problems in healthy older adults. Future investigation of the potentially moderating effects of cognitive and behavioral compensatory strategies may be beneficial.
doi:10.1017/S1355617711001263
PMCID: PMC3268683  PMID: 22032776
aging; prospective memory; retrospective memory; activities of daily living; neuropsychological assessment; geropsychology
16.  Self-Generation Enhances Verbal Recall in Individuals Infected with HIV 
Despite the prevalence of HIV-associated episodic memory impairment and its adverse functional impact, there are no empirically-validated cognitive rehabilitation options for HIV-infected persons. The present study examined the self-generation approach, which is theorized to enhance new learning by elaborating and deepening encoding. Participants included 54 HIV-infected and 46 seronegative individuals, who learned paired word associates in both self-generated and didactic encoding experimental conditions. Results revealed main effects of HIV serostatus and encoding condition, but no interaction. Planned comparisons showed that both groups recalled significantly more words learned in the self-generation condition, and that HIV+ individuals recalled fewer words overall compared to their seronegative counterparts at delayed recall. Importantly, HIV+ participants with clinical memory impairment evidenced comparable benefits of self-generation compared to unimpaired HIV+ subjects. Self-generation strategies may improve verbal recall in individuals with HIV infection and may therefore be an appropriate and potentially effective cognitive rehabilitation tool in this population.
doi:10.1017/S135561771100124X
PMCID: PMC3268686  PMID: 22014146
Episodic memory; neuropsychological assessment; AIDS dementia complex; generation effect (learning); cognition; cognitive rehabilitation
17.  Time-Based Prospective Memory Predicts Engagement in Risk Behaviors Amongst Substance Users: Results from Clinical and Nonclinical Samples 
Deficits in prospective memory (PM; i.e., enacting previously learned actions at the right occasion) and risky decision-making (i.e., making choices with a high chance of undesirable/dangerous outcomes) are both common amongst individuals with substance use disorders (SUD). Previous research has raised the possibility of a specific relationship between PM and risk-taking, and the present study aimed to systematically study if PM provides unique variance in the prediction of risky decision-making. Two samples were included: 1) a group of 45 individuals with SUD currently in treatment, and 2) a nonclinical group of 59 university students with high-risk drinking and/or substance use. Regression analyses indicated that time-based, but not event-based, PM predicted increased risky behavior (e.g., risky sexual practices and criminal behaviors) in both groups after controlling for demographic, psychiatric, and substance use variables, as well as other neuropsychological functions. The current findings contribute to the growing literature supporting the role of PM as a predictor of everyday functioning, and suggest that cognitive rehabilitation may be an important avenue of research as an adjunct to traditional substance use treatment, particularly in addressing the potential adverse effects of PM deficits in the implementation of treatment-related homework activities and risk management strategies.
doi:10.1017/S1355617712001361
PMCID: PMC3694418  PMID: 23312588
Prospective memory; risky behavior; risky decision-making; substance abuse; episodic memory; executive functions; cognition
18.  Risky decision-making in HIV-associated neurocognitive disorders (HAND) 
The Clinical neuropsychologist  2012;27(2):256-275.
Individuals infected with HIV show moderate deficits in decision-making, but the ecological relevance of such deficits on everyday functioning has not previously been described. This study sought to examine the magnitude, cognitive correlates, and everyday functioning impact of risky decision-making impairment in HIV-associated neurocognitive disorders (HAND). Participants included 68 HIV+ individuals with HAND, 78 HIV+ individuals without HAND, and 51 HIV- comparison participants, who were administered the Iowa Gambling Task (IGT) alongside a comprehensive neuropsychological test battery and self-report measures assessing aspects of everyday functioning. HIV+ individuals with HAND performed more poorly on the IGT relative to the other two groups, most notably during the last three trial blocks. Within the HIV+ group, IGT performance during the last three trial blocks was most strongly associated with cognitive flexibility, but was not significantly related to declines in instrumental activities of daily living (IADLs), unemployment, or medication non-adherence. While overall IGT performance across the last three trial blocks may be helpful diagnostically in identifying decision-making impairment in HAND, examination of alternate, more specific metrics (e.g., individual deck selections across trial blocks) may be more useful in delineating the role of poor decision-making in HIV-related disability, and should be examined in future research.
doi:10.1080/13854046.2012.740077
PMCID: PMC3609907  PMID: 23181946
HIV; cognitive impairment; decision-making; everyday functioning; cognitive flexibility
19.  Prospective Memory and Antiretroviral Medication Non-Adherence in HIV: An Analysis of Ongoing Task Delay Length Using the Memory for Intentions Screening Test 
Using McDaniel & Einstein’s (2000) multi-process framework, the current study examined whether the length of prospective memory (PM) delay intervals as measured by the 2- and 15- minute subscales of the Memory for Intentions Screening Test (MIST) have differential predictive value for antiretroviral (ARV) adherence. Participants included 74 HIV-infected individuals whose ARV adherence was tracked with an electronic monitoring system. Participants were classified as “adherent” (n = 49) or “non-adherent” (n = 25) based on recorded pill bottle openings of ≥90% of prescribed doses over 30 days. An adherence group by MIST delay interval interaction was observed, such that non-adherent participants had worse performance on the 15-min, but not 2-min delay PM MIST subscales. The observed MIST 15- min delay effects were significantly more pronounced on time- versus event-cued PM trials. Long-delay time-based PM was predictive of non-adherence independent of demographics, mood state, self-reported adherence, and general cognitive functioning. Findings from this clinical study indicate that ARV non-adherence may be particularly associated with deficits in strategic cue monitoring over longer PM delays, which may inform interventions to improve adherence among persons living with HIV infection.
doi:10.1017/S1355617712001051
PMCID: PMC3693472  PMID: 23095304
episodic memory; medication adherence; everyday functioning; neuropsychological assessment; executive functions; AIDS dementia complex
20.  An examination of the age-prospective memory paradox in HIV-infected adults 
The age-prospective memory (PM) paradox asserts that, despite evidence of age-associated PM deficits on laboratory tasks, older adults perform comparably to (or better than) young adults on naturalistic PM tasks. This study examined the age-PM paradox in older HIV-infected individuals, who represent a growing epidemic and may be at heightened risk for adverse neurocognitive and everyday functioning outcomes. Participants included 88 older (50+ years) and 53 younger (≤40 years) HIV-infected individuals as well as 54 older and 59 younger seronegative adults who completed both laboratory and naturalistic time-based PM tasks. Similar interactions were observed in both the seropositive and the seronegative samples, such that the older participants demonstrated significantly lower laboratory-based PM than the younger groups, but not on the naturalistic PM trial. Secondary analyses within the HIV+ sample revealed that naturalistic task success was indirectly associated with greater self-reported use of PM-based and external compensatory strategies in the daily lives of older, but not younger, HIV+ adults. Study findings suggest that, although older HIV-infected adults exhibit moderate PM deficits on laboratory measures versus their younger counterparts, such impairments are paradoxically not evident on ecologically relevant naturalistic PM activities in daily life, perhaps related to effective utilization compensatory strategies.
doi:10.1080/13803395.2011.604027
PMCID: PMC3327134  PMID: 21992453
Episodic memory; Aging; Neuropsychological assessment; AIDS dementia complex; Cognition
21.  Prospective Memory Deficits Are Associated with Unemployment in Persons Living With HIV Infection 
Rehabilitation Psychology  2011;56(1):77-84.
Objective
To determine whether deficits in prospective memory (i.e., “remembering to remember”) confer an increased risk of unemployment in individuals living with chronic HIV infection.
Methods
Fifty-nine Unemployed and 49 Employed individuals with HIV infection underwent comprehensive neuropsychological and medical evaluations, including measures of prospective memory.
Results
The Unemployed participants demonstrated significantly lower performance on time- and event-based prospective memory, which was primarily characterized by errors of omission. Importantly, prospective memory impairment was an independent predictor of unemployment when considered alongside other neurocognitive abilities, mood disturbance, and HIV disease severity.
Conclusions
Prospective memory impairment is a salient predictor of unemployment in persons living with HIV infection and might be considered in screening for unemployment risk and developing vocational rehabilitation plans.
doi:10.1037/a0022753
PMCID: PMC3264430  PMID: 21401289
AIDS dementia complex; employment; prospective memory; episodic memory; everyday functioning
22.  HIV-associated Prospective Memory Impairment in the Laboratory Predicts Failures on a Semi-naturalistic Measure of Health Care Compliance 
The Clinical Neuropsychologist  2010;24(6):945-962.
HIV-associated neurocognitive impairment, particularly in the domain of prospective memory (ProM), increases the risk of poor everyday functioning outcomes, including medication non-adherence. However, whether ProM plays a role in health care compliance outside of the realm of medication adherence remains to be determined. This study evaluated the hypothesis that ProM is an independent predictor of failure to comply with non-medication related instructions akin to those commonly given by health care providers. Participants were 139 HIV-infected adults who underwent medical, psychiatric, and neuropsychological assessments, including a laboratory-based measure of ProM. To assess real-world compliance, participants were instructed to call the examiner 24 hours after the evaluation and report how many hours they had slept. Individuals who failed to correctly comply with these instructions (n=104) demonstrated significantly lower performance on both time- and event-based ProM at baseline than the compliant group (n=35), an effect that was primarily driven by errors of omission. ProM remained a significant predictor of noncompliance after controlling for potential confounders, including demographics (e.g., education), traditional cognitive measures of retrospective memory and executive functions, and psychiatric factors (e.g., depression). Results support the hypothesis that ProM plays a unique role in compliance with health care instructions for HIV disease management and may inform interventions designed to improve treatment outcomes.
doi:10.1080/13854046.2010.501343
PMCID: PMC3268682  PMID: 20661839
Episodic memory; AIDS dementia complex; compliance; adherence; everyday functioning; human immunodeficiency virus
23.  Methamphetamine use and neuropsychiatric factors are associated with antiretroviral nonadherence 
AIDS care  2012;24(12):1504-1513.
The present study assesses the impact of methamphetamine (METH) on antiretroviral (ART) adherence among HIV+ persons, as well as examines the contribution of neurocognitive impairment and other neuropsychiatric factors (i.e., major depressive disorder (MDD), Antisocial Personality Disorder (ASPD), and Attention Deficit Disorder (ADHD)) for ART nonadherence. We examined HIV+ persons with DSM-IV-diagnosed lifetime history of METH abuse/dependence (HIV+/METH+; n = 67) as compared to HIV+ participants with no history of METH abuse/dependence (HIV+/METH−; n = 50). Ancillary analyses compared these groups with a small group of HIV+/METH+ persons with current METH abuse/dependence (HIV+/CU METH+; n = 8). Nonadherence was defined as self-report of any skipped ART dose in the last four days. Neurocognitive functioning was assessed with a comprehensive battery, covering seven neuropsychological domains. Lifetime METH diagnosis was associated with higher rates of detectable levels of plasma and CSF HIV RNA. When combing groups (i.e., METH+ and METH− participants), univariate analyses indicated co-occurring ADHD, ASPD, and MDD predicted ART nonadherence (p’s<0.10; not lifetime METH status or neurocognitive impairment). A significant multivariable model including these variables indicated that only MDD uniquely predicted ART nonadherence after controlling for the other variables (p<0.05). Ancillary analyses indicated that current METH users (use within 30 days) were significantly less adherent (50% prevalence of nonadherence) than lifetime METH+ users and HIV+/METH-participants, and that neurocognitive impairment was associated with nonadherence (p’s<0.05). METH use disorders are associated with worse HIV disease outcomes and ART medication nonadherence. Interventions often target substance use behaviors alone to enhance antiretroviral treatment outcomes; however, in addition to targeting substance use behaviors, interventions to improve ART adherence may also need to address coexisting neuropsychiatric factors and cognitive impairment to improve ART medication taking.
doi:10.1080/09540121.2012.672718
PMCID: PMC3466384  PMID: 22530794
HIV/AIDS; Cognition; Medication Adherence; Antiretroviral; Methamphetamine
24.  HIV-associated Deficits in Action (Verb) Generation May Reflect Astrocytosis 
Commensurate with the hypothesized neural dissociation between verb and noun generation, research in HIV infection shows that, relative to noun fluency, action (verb) fluency is disproportionately impaired, more strongly related to executive dysfunction, and more sensitive to declines in everyday functioning. However, whether the neurobiological correlates of HIV-associated deficits in verb and noun generation are separable have not heretofore been investigated. The present study examined the biomarker correlates of action and noun fluency in 74 participants with HIV infection. Biomarkers of viral burden, neuroaxonal damage, macrophage activation, neuroprotection, inflammation, and astrocytosis were measured in plasma and cerebrospinal fluid (CSF). Deficits in action, but not noun generation, were significantly associated with higher CSF levels of S100β, a marker of astrocyte activation, even after controlling for antiretroviral therapy, current immune compromise, and general cognitive impairment. Concurrent validity for the frontal systems hypothesis of verb generation was provided by post-hoc analyses demonstrating that S100β was also associated with measures of executive functions, but not semantic memory or psychomotor speed. Overall, these findings suggest that HIV-associated impairment in action fluency, and executive dysfunction more generally, may reflect astrocytosis (i.e., elevated S100 β). Complementing the literature in HIV and other clinical populations with frontal systems involvement, these data also support the possible neurobiological dissociation of noun and verb generation.
doi:10.1080/13803390903264130
PMCID: PMC2878376  PMID: 19844819
Human immunodeficiency virus; cognitive processes; verbal fluency; verbs; frontal lobe
25.  The Semantic Relatedness of Cue-Intention Pairings Influences Event-Based Prospective Memory Failures in Older Adults with HIV Infection 
HIV infection and aging are each independently associated with prospective memory (ProM) impairment, which increases the risk of poor functional outcomes, including medication adherence. The incidence and prevalence of HIV infection among older adults has increased in recent years, thereby raising questions about the combined effects of these risk factors on ProM. In the present study, 118 participants were classified into four groups on the basis of HIV serostatus and age (i.e., ≤ 40 years and ≥ 50 years). Results showed significant additive effects of HIV and aging on event-based ProM, with the greatest deficits evident in the older HIV+ group, even after controlling for other demographic factors and potential medical, and psychiatric confounds. Event-based ProM impairment was particularly apparent in the older HIV+ group on trials for which the retrieval cue and intention were not semantically related. Worse performance on the semantically unrelated cue-intention trials was associated with executive dysfunction, older age, and histories of immunocompromise in the older HIV+ cohort. These data suggest that older HIV-infected adults are significantly less proficient at engaging the strategic encoding and retrieval processes required to a execute a future intention when the cue is unrelated to the intended action, perhaps secondary to greater neuropathological burden in the prefrontostriatal systems critical to optimal ProM functioning.
doi:10.1080/13803390903130737
PMCID: PMC2854853  PMID: 19763997
Human immunodeficiency virus; Episodic memory; aging; AIDS dementia complex; multi-process theory

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