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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.  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
5.  Lower Cognitive Reserve Among Individuals with Syndromic HIV-associated Neurocognitive Disorders (HAND) 
AIDS and behavior  2012;16(8):2279-2285.
HIV-seropositive individuals with low cognitive reserve are at high risk for developing HIV-associated neurocognitive disorders (HAND). The present study evaluated the hypothesis that cognitive reserve would also play a unique role in the expression of everyday functioning complications among those with HAND (i.e., syndromic versus subsyndromic impairment). Eighty-six individuals with HIV infection were evaluated; 53 individuals evidenced normal neurocognitive performance, 16 had subsyndromic HAND (i.e., Asymptomatic Neurocognitive Impairment), and 17 were diagnosed with a syndromic HAND based on a comprehensive neurobehavioral evaluation. Cognitive reserve represented a combined score including years of education, estimated verbal IQ, and highest occupational attainment. The groups were comparable (e.g. demographics), and the HAND groups had similar rates of global neurocognitive impairment. The Syndromic HAND group evidenced lower reserve scores relative to both other groups, suggesting that HIV-infected individuals with high cognitive reserve more effectively counteract their neurocognitive impairment to maintain independence in daily living activities.
doi:10.1007/s10461-012-0229-7
PMCID: PMC3443502  PMID: 22677976
Cognitive reserve; HIV/AIDS; activities of daily living; neuropsychological assessment
6.  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
7.  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
8.  Neurocognitive deficits are associated with unemployment in chronic methamphetamine users 
Drug and alcohol dependence  2012;125(0):146-153.
Background
Unemployment rates are high among chronic methamphetamine (MA) users and carry a significant economic burden, yet little is known about the neurocognitive and psychiatric predictors of employment in this vulnerable population.
Methods
The present study examined this issue in 63 participants with recent MA dependence and 47 comparison subjects without histories of MA use disorders. All participants completed a comprehensive neurocognitive, psychiatric and neuromedical evaluation. Individuals with HIV infection, severe neuropsychological or psychiatric conditions that might affect cognition (e.g., seizure disorder, schizophrenia), or a positive Breathalyzer or urine toxicology screen on the day of testing were excluded.
Results
Consistent with previous research, a logistic regression revealed MA dependence as a significant, independent predictor of full-time unemployment status. Within the MA-dependent sample, greater impairment in global neurocognitive functioning and history of injection drug use emerged as significant independent predictors of unemployment status. The association between worse global cognitive functioning and unemployment was primarily driven by deficits in executive functions, learning, verbal fluency, and working memory.
Conclusion
These findings indicate that neurocognitive deficits play a significant role in the higher unemployment rates of MA-dependent individuals, and highlight the need for vocational rehabilitation and supported employment programs that assess and bolster cognitive skills in this population.
doi:10.1016/j.drugalcdep.2012.04.002
PMCID: PMC3735422  PMID: 22560676
Functional status; Substance abuse; Cognitive impairment; Neuropsychological assessment; Employment
9.  Altered prefronto-striato-parietal network response to mental rotation in HIV 
Journal of neurovirology  2012;18(1):74-79.
The present study used functional magnetic resonance imaging to examine the neural substrates of mental rotation in 11 individuals with HIV infection and 13 demographically similar HIV seronegative volunteers. Individuals with HIV showed increased brain response to mental rotation in prefrontal and posterior parietal cortices, striatum, and thalamus, with significant HIV by angle interactions emerging in the prefrontal cortex and caudate. Results indicate that HIV infection is associated with altered brain response to mental rotation in fronto-striato-parietal pathways, which may reflect compensatory strategies, recruitment of additional brain regions, and/or increased neuroenergetic demands during mental rotation needed to offset underlying HIV-associated neural injury.
doi:10.1007/s13365-011-0072-z
PMCID: PMC3729929  PMID: 22271019
Human immunodeficiency virus; Mental rotation; Spatial cognition; Functional magnetic resonance imaging
10.  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
11.  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
12.  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
13.  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
14.  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
15.  Are Time- and Event-based Prospective Memory Comparably Affected in HIV Infection?† 
According to the multi-process theory of prospective memory (ProM), time-based tasks rely more heavily on strategic processes dependent on prefrontal systems than do event-based tasks. Given the prominent frontostriatal pathophysiology of HIV infection, one would expect HIV-infected individuals to demonstrate greater deficits in time-based versus event-based ProM. However, the two prior studies examining this question have produced variable results. We evaluated this hypothesis in 143 individuals with HIV infection and 43 demographically similar seronegative adults (HIV−) who completed the research version of the Memory for Intentions Screening Test, which yields parallel subscales of time- and event-based ProM. Results showed main effects of HIV serostatus and cue type, but no interaction between serostatus and cue. Planned pair-wise comparisons showed a significant effect of HIV on time-based ProM and a trend-level effect on event-based ProM that was driven primarily by the subset of participants with HIV-associated neurocognitive disorders. Nevertheless, time-based ProM was more strongly correlated with measures of executive functions, attention/working memory, and verbal fluency in HIV-infected persons. Although HIV-associated deficits in time- and event-based ProM appear to be of comparable severity, the cognitive architecture of time-based ProM may be more strongly influenced by strategic monitoring and retrieval processes.
doi:10.1093/arclin/acr020
PMCID: PMC3081684  PMID: 21459901
AIDS dementia complex; Episodic memory; Executive functions; Neuropsychological assessment
16.  Misremembering Future Intentions in Methamphetamine Dependent Individuals 
The Clinical Neuropsychologist  2011;25(2):269-286.
Methamphetamine (MA) dependence is associated with neural abnormalities (e.g., frontal systems neurotoxicity) and corresponding cognitive deficits, including impairment in episodic memory and executive functions. This study evaluated the hypothesis that MA use is associated with impairment in memory for intentions, or prospective memory (ProM), which is an ecologically relevant aspect of episodic memory that involves the execution of a previously encoded intention at an appropriate moment in the future and is known to rely on frontal systems integrity. Thirty-nine MA-dependent individuals and 26 demographically similar non-MA-using comparison subjects were administered the Memory for Intentions Screening Test (MIST). The MA group performed significantly lower than the comparison participants on overall ProM, an effect that could not be better explained by demographics, psychiatric factors, infectious disease comorbidity, or other substance use disorders. The ProM impairment observed in the MA group was comparable on time- and event-based tasks and was marked by an increased rate of task substitution (i.e., intrusions) and loss of time (e.g., early responding) errors. Within the MA cohort, ProM impairment was associated with executive dysfunction and earlier age at first MA use. Findings suggest that individuals with MA dependence experience difficulty in the strategic components involved in the retrieval of future intentions and are discussed with regard to their implications for everyday functioning.
doi:10.1080/13854046.2010.546812
PMCID: PMC3264429  PMID: 21331980
Prospective memory; methamphetamine; episodic memory; executive functions; time perception; cognition
17.  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
18.  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
19.  Spontaneous Strategy Use Protects Against Visual Working Memory Deficits in Older Adults Infected with HIV 
Recent studies suggest that older human immunodeficiency virus (HIV)-infected adults are at particular risk for HIV-associated neurocognitive disorders (HAND), including dementia. Deficits in attention/working memory are posited to play a central role in the development of HAND among older adults. The aim of the present study was to examine the possible protective benefits of spontaneous strategy use during a visual working memory task in 46 older and 42 younger adults infected with HIV. Results revealed a significant interaction between age and strategy use, with older adults who used a meta-cognitive strategy demonstrating superior working memory performance versus non-strategy users. This effect was not observed in the younger HIV-infected sample and was not better explained by possible confounding factors, such as education, comorbid medical conditions, or HIV disease severity. Within the older group, strategy use was associated with better executive functions and higher estimated verbal intelligence. Findings from this study suggest that working memory declines in older HIV-infected adults are moderated by the use of higher-level mnemonic strategies and may inform cognitive neurorehabilitation efforts to improve cognitive and everyday functioning outcomes in older persons living with HIV infection.
doi:10.1093/arclin/acq069
PMCID: PMC2979348  PMID: 20876195
Human immunodeficiency virus; Working memory; Aging; Strategies; Neuropsychology
20.  Is Prospective Memory a Dissociable Cognitive Function in HIV infection? 
An emerging literature indicates that HIV infection is associated with deficits in prospective memory (ProM), or the ability to execute a future intention. This literature offers evidence of neurobiological dissociability of ProM from other cognitive abilities and its incremental ecological validity as a predictor of poorer everyday functioning outcomes (e.g., medication non-adherence). The present study evaluated the hypothesis that ProM represents a unique cognitive construct in HIV disease. A confirmatory 4-factor structural equation model was tested on data derived from 162 participants with HIV. The model posited that measures of ProM comprise a unique factor, apart from standard clinical tests of retrospective memory, executive functions, and motor skills. The fit of the model was evaluated using the Bollen-Stine bootstrap method and indicated a 4-factor model with measures of ProM loading on a unique factor fit the data well, and better than a model with a single common factor hypothesized to drive cognitive performance. The results of this study lend further evidence to the dissociability of ProM in HIV infection, are consistent with prior studies in healthy adults, and contribute to a growing literature on the construct validity of ProM in HIV disease.
doi:10.1080/13803391003596470
PMCID: PMC2912973  PMID: 20425662
Human Immunodeficiency Virus; AIDS dementia complex; Neuropsychological tests; Cognitive science; Episodic memory
21.  Neurocognitive Consequences of HIV Infection in Older Adults: An Evaluation of the “Cortical” Hypothesis 
AIDS and behavior  2011;15(6):1187-1196.
The incidence and prevalence of older adults living with HIV infection is increasing. Recent reports of increased neuropathologic and metabolic alterations in older HIV+ samples, including increased cortical beta-amyloid, have led some researchers to suggest that aging with HIV may produce a neuropsychological profile akin to that which is observed in “cortical” dementias (e.g., impairment in memory consolidation). To evaluate this possibility, we examined four groups classified by HIV serostatus and age (i.e., younger ≤40 years and older ≥50 years): (1) Younger HIV− (n = 24); (2) Younger HIV+ (n = 24); (3) Older HIV− (n = 20); and (4) Older HIV+ (n = 48). Main effects of aging were observed on episodic learning and memory, executive functions, and visuoconstruction, and main effects of HIV were observed on measures of verbal learning and memory. The interaction of age and HIV was observed on a measure of verbal recognition memory, which post hoc analyses showed to be exclusively attributed to the superior performance of the younger HIV seronegative group. Thus, in this sample of older HIV-infected individuals, the combined effects of HIV and aging do not appear to result in a “cortical” pattern of cognitive deficits.
doi:10.1007/s10461-010-9815-8
PMCID: PMC3110599  PMID: 20865313
Human immunodeficiency virus; Aging; Cognition; Neuropsychological tests; Episodic memory
22.  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
23.  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
24.  A Brief Report on Mental Rotation of Hands in HIV Infection: Neuropsychological Evidence of Dysfunction in Fronto-striato-parietal Networks 
Mental rotation, the ability to manipulate three-dimensional objects in space, is a widely-studied and neurally-complex aspect of spatial cognition that has been largely ignored in the HIV literature. The present study reports evidence of a significant interaction between HIV serostatus and performance on mental rotation tasks, whereby individuals with HIV (n = 19) committed a greater number of errors than demographically similar seronegative persons (n = 15) on Luria's {1} hand rotation task (d = 0.74, p < 0.05), but not on the corresponding parallelogram rotation task (p > .10). Hand rotation errors were associated with worse performance on measures of executive functions and working memory, but not with measures of visuoperception. Considered in the context of the preferential frontostriatal neuropathology of HIV-associated neurocognitive disorders, these preliminary findings suggest that the observed deficit in the mental rotation of hands may arise from a disrupted fronto-striato-parietal network.
doi:10.1176/appi.neuropsych.22.1.115
PMCID: PMC2945904  PMID: 20160219
HIV; AIDS; spatial ability; neuropsychological assessment; executive functions
25.  Neurocognitive Consequences of HIV Infection in Older Adults: An Evaluation of the “Cortical” Hypothesis 
AIDS and Behavior  2010;15(6):1187-1196.
The incidence and prevalence of older adults living with HIV infection is increasing. Recent reports of increased neuropathologic and metabolic alterations in older HIV+ samples, including increased cortical beta-amyloid, have led some researchers to suggest that aging with HIV may produce a neuropsychological profile akin to that which is observed in “cortical” dementias (e.g., impairment in memory consolidation). To evaluate this possibility, we examined four groups classified by HIV serostatus and age (i.e., younger ≤40 years and older ≥50 years): (1) Younger HIV− (n = 24); (2) Younger HIV+ (n = 24); (3) Older HIV− (n = 20); and (4) Older HIV+ (n = 48). Main effects of aging were observed on episodic learning and memory, executive functions, and visuoconstruction, and main effects of HIV were observed on measures of verbal learning and memory. The interaction of age and HIV was observed on a measure of verbal recognition memory, which post hoc analyses showed to be exclusively attributed to the superior performance of the younger HIV seronegative group. Thus, in this sample of older HIV-infected individuals, the combined effects of HIV and aging do not appear to result in a “cortical” pattern of cognitive deficits.
doi:10.1007/s10461-010-9815-8
PMCID: PMC3110599  PMID: 20865313
Human immunodeficiency virus; Aging; Cognition; Neuropsychological tests; Episodic memory

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