Attention-Deficit/Hyperactivity Disorder (ADHD) is widely regarded as a common comorbidity of methamphetamine (MA) dependence, but the frequency, persistence, and real-world impact of ADHD among MA users is not known.
Four hundred individuals with MA use disorders within 18 months of evaluation and 355 non-MA using comparison subjects completed a comprehensive neuropsychiatric research battery, including self-report measures of everyday functioning.
In logistic regression models adjusting for potential confounds, lifetime diagnoses of ADHD as determined by a structured clinical interview were significantly more prevalent among the MA participants (21%) versus comparison subjects (6%), particularly the hyperactive and combined subtypes. MA use was also associated with an increased persistence of combined subtype of ADHD into adulthood. Among the MA users, lifetime ADHD diagnoses were uniquely associated with greater concurrent risk of declines in instrumental activities of daily living, elevated cognitive symptoms in day-to-day life, and unemployment.
Findings indicate that ADHD is prevalent among chronic MA users, who are at increased risk for persistence of childhood diagnoses of ADHD into their adult years. ADHD also appears to play an important role in MA-associated disability, indicating that targeted ADHD screening and treatment may help to improve real-world outcomes for individuals with MA use disorders.
Substance Abuse; Developmental Disorder; Comorbidity; Functioning; Disability; Neuropsychiatry
The acute and early period of HIV-1 infection (AEH) is characterized by neuroinflammatory and immunopathogenic processes that can alter the integrity of neural systems and neurocognitive functions. However, the extent to which central nervous system changes in AEH confer increased risk of real-world functioning (RWF) problems is not known. In the present study, 34 individuals with AEH and 39 seronegative comparison participants completed standardized neuromedical, psychiatric, and neurocognitive research evaluations, alongside a comprehensive assessment of RWF that included cognitive symptoms in daily life, basic and instrumental activities of daily living, clinician-rated global functioning, and employment. Results showed that AEH was associated with a significantly increased risk of dependence in RWF, which was particularly elevated among AEH persons with global neurocognitive impairment (NCI). Among those with AEH, NCI (i.e., deficits in learning and information processing speed), mood disorders (i.e., Bipolar Disorder), and substance dependence (e.g., methamphetamine dependence) were all independently predictive of RWF dependence. Findings suggest that neurocognitively impaired individuals with AEH are at notably elevated risk of clinically significant challenges in normal daily functioning. Screening for neurocognitive, mood, and substance use disorders in AEH may facilitate identification of individuals at high risk of functional dependence who may benefit from psychological and medical strategies to manage their neuropsychiatric conditions.
Infectious disease; Disability; Substance use; Neuropsychology; AIDS-related Dementia
To compare temporal order memory in older adults with and without HIV infection.
The frontal and temporal lobes play a key role in temporal order memory for items in a sequence. HIV-associated episodic memory deficits correlate with damage to neocortical interneurons in the fronto-striato-thalamo-cortical pathway and with atypical activation of the medial temporal lobes. Therefore, temporal order memory may be sensitive to neuropathological changes in individuals with HIV.
In this study, 50 HIV-seropositive individuals aged ≥ 50 years and 50 seronegative controls performed a computerized visuospatial temporal order memory task. During the sample phase of each trial, participants were shown circles presented 1 at a time in a random sequence at the end of each of the 8 arms of a radial maze. During the choice phase, they were shown the maze with a circle at the ends of 2 of the arms and asked which circle had appeared earlier than the other in the original sequence.
Performance in both groups improved as a function of greater temporal separation between circle presentations. However, the HIV group had significantly worse memory impairment across all temporal separations, and the impairment was independently associated with clinical deficits in executive function and delayed retrospective memory.
Our results extend prior findings that HIV is associated with deficits in strategic aspects of memory encoding and retrieval. The neural mechanisms warrant further research, as do potential impacts on everyday function, eg, adherence to antiretroviral drug regimens.
HIV; temporal order; visuospatial; episodic memory; executive function
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.
HIV/AIDS; Prospective memory; Executive functions; Time perception; AIDS dementia complex
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.
HIV; AIDS dementia complex; cognition; cognitive rehabilitation
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.
HIV; substance abuse; viral load; neuropsychiatry; AIDS dementia complex
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.
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.
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.
HIV; cognition; HIV-associated neurocognitive disorders; screening measures; HIV dementia scale
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.
Apathy is a relatively common psychiatric syndrome in HIV infection, but little is known about its neural correlates. In the present study, we examined the associations between apathy and diffusion tensor imaging (DTI) indices in key frontal white matter regions in the thalamocorticostriatal circuit that has been implicated in the expression of apathy. Nineteen participants with HIV infection and 19 demographically comparable seronegative comparison subjects completed the Apathy subscale of the Frontal Systems Behavioral Scale as a part of a comprehensive neuropsychiatric research evaluation. When compared to the seronegative participants, the HIV+ group had significantly more frontal white matter abnormalities. Within HIV+ persons, and as predicted, higher ratings of apathy were associated with greater white matter alterations in the anterior corona radiata, genu, and orbital medial prefrontal cortex. The associations between white matter alterations and apathy were independent of depression and were stronger among participants with lower current CD4 counts. All told, these findings indicate that apathy is independently associated with white matter abnormalities in anterior, medial brain regions in persons infected with HIV, particularly in the setting of lower current immune functioning, which may have implications for antiretroviral therapy.
Diffusion tensor imaging; apathy; HIV/AIDS; Prefrontal cortex; depression
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.
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.
AIDS Dementia Complex; Aging; Prospective memory; Quality of life; Functional status; Health status
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.
Planned behavior; executive functioning; employment status; activities of daily living; higher order processes
To determine whether HIV infection and aging act synergistically to disrupt everyday functioning.
Cross-sectional, factorial study of everyday functioning in the context of HIV serostatus and age (≤ 40 years vs ≥ 50 years).
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.
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.
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.
HIV; aging; assessment; daily functioning; health status; disability
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.
HIV; medication management; neuropsychological functioning; adherence; construct validity; instrumental activities of daily living
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.
Methamphetamine; Substance abuse; Executive dysfunction; Behavioral disinhibition; Neuropsychological assessment; Activities of daily living
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.
infectious disease; verbal fluency; semantic memory; cognitive rehabilitation; executive functions; cognitive neuropsychology
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.
Prospective memory; HIV/AIDS; episodic memory; executive functions; time perception; AIDS Dementia Complex
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.
Human immunodeficiency virus; episodic memory; neuropsychological assessment; encoding; consolidation; retrieval
Methamphetamine (METH) use and human immunodeficiency virus (HIV) infection are highly comorbid, and both are associated with increased prevalence of affective distress. Delineating the trajectory of affective distress in the context of METH dependence and HIV infection is important given the implications for everyday functional impairment, adverse health behaviors, and increased risk for adverse health outcomes.
We conducted a five-year longitudinal investigation involving 133 METH-dependent (74 HIV seropositive) and 163 non-METH-dependent (90 HIV seropositive) persons to examine both long-standing patterns and transient changes in affective distress. Mixed-effect regression models with random subject-specific slopes and intercepts evaluated the effect of METH dependence, HIV serostatus, and related variables on affective distress, as measured by the Profile of Mood States.
Transient changes in affective distress were found to be greater among those with a diagnosis of current MDD, briefer durations of abstinence from METH, and higher quantity of METH consumed. Weak associations were observed among static (time-independent predictors) covariates and long-standing patterns in affective distress.
Study lacked data pertaining to the participants’ involvement in METH treatment and relied on respondent-driven sampling.
Our longitudinal investigation of the trajectory of affective distress indicated that specific and dynamic indices of current METH use were associated with greater transient changes in mood. In the evaluation and treatment of affective distress, recency and quantity of current METH use are important to consider given their association with heightened affective distress and mood instability over time.
Affective distress; Methamphetamine; Dependence; HIV; Longitudinal
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.
aging; prospective memory; retrospective memory; activities of daily living; neuropsychological assessment; geropsychology
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.
Episodic memory; neuropsychological assessment; AIDS dementia complex; generation effect (learning); cognition; cognitive rehabilitation
Risky decision-making is commonly observed in persons at risk for and infected with HIV and is associated with executive dysfunction. Yet it is currently unknown whether HIV alters brain processing of risk-taking decision-making.
This study examined the neural substrate of a risky decision-making task in 21 HIV seropositive (HIV+) and 19 seronegative (HIV-) comparison participants. Functional magnetic resonance imaging was conducted while participants performed the risky-gains task, which involves choosing among safe (20 cents) and risky (40/80 cent win or loss) choices. Linear mixed effects analyses examining group and decision type were conducted. Robust regressions were performed to examine the relationship between nadir CD4 count and Kalichman sexual compulsivity and brain activation in the HIV+ group. The overlap between the task effects and robust regressions was explored.
Although there were no serostatus effects in behavioral performance on the risky-gains task, HIV+ individuals exhibited greater activation for risky choices in the basal ganglia, i.e. the caudate nucleus, but also in the anterior cingulate, dorsolateral prefrontal cortex, and insula relative to the HIV- group. The HIV+ group also demonstrated reduced functional responses to safe choices in the anterior cingulate and dorsolateral prefrontal cortex relative to the HIV- group. HIV+ individuals with higher nadir CD4 count and greater sexual compulsivity displayed lower differential responses to safe versus risky choices in many of these regions.
This study demonstrated fronto-striatal loop dysfunction associated with HIV infection during risky decision-making. Combined with similar between-group task behavior, this suggests an adaptive functional response in regions critical to reward and behavioral control in the HIV+ group. HIV-infected individuals with higher CD4 nadirs demonstrated activation patterns more similar to seronegative individuals. This suggests that the severity of past immunosuppression (CD4 nadir) may exert a legacy effect on processing of risky choices in the HIV-infected brain.
Higher levels of cognitive reserve (CR) can be protective against the neuropsychological manifestation of neural injury across a variety of clinical disorders. However, the role of CR in the expression of neurocognitive deficits among persons infected with the hepatitis C virus (HCV) is not well understood. Thirty-nine HCV-infected participants were classified as having either high (n=19) or low (n=20) CR based on educational attainment, oral word reading, and IQ scores. A sample of 40 demographically comparable healthy adults (HA) was also included. All participants completed the Neuropsychological Assessment Battery (NAB), Delis-Kaplan Executive Function System (D-KEFS), and Behavioral Rating Inventory of Executive Function, Adult Version (BRIEF-A). Linear regression analyses, controlling for gender, depression and lifetime substance use disorders, found significant effects of HCV/CR group on verbal fluency, executive functions, and daily functioning T-scores, but not in learning or the BRIEF-A. Pairwise comparisons revealed that the HCV group with low CR performed significantly below the HCV high CR and HA cohorts, who did not differ from one another. Findings indicate that higher levels of CR may be a protective factor in the neurocognitive and real-world manifestation of neural injury commonly associated with HCV infection.
Hepatitis C; Cognitive reserve; Neuropsychological assessment; Daily functioning
HIV coreceptor usage of CXCR4 (X4) is associated with decreased CD4+ T-cell counts and accelerated disease progression, but the role of X4 tropism in HIV-associated neurocognitive disorders (HAND) has not previously been described.
This longitudinal study evaluated data on 197 visits from 72 recently HIV-infected persons who had undergone up to 4 sequential neurocognitive assessments over a median of 160 days (IQR 138–192). Phenotypic tropism testing (Trofile ES, Monogram, Biosciences) was performed on stored blood samples. Multivariable mixed model repeated measures regression was used to determine the association between HAND and dual-mixed (DM) viral tropism, estimated duration of infection (EDI), HIV RNA, CD4 count and problematic methamphetamine use.
Six subjects (8.3%) had dual mixed tropism (DM) at their first neurocognitive assessment and four converted to DM in subsequent sampling (for total of 10 DM) at a median EDI of 10.1 months (IQR 7.2–12.2). There were 44 (61.1%) subjects who demonstrated HAND on at least one study visit. HAND was associated with DM tropism (odds ratio 4.4, 95% CI 0.9–20.5) and shorter EDI (odds ratio 1.1 per month earlier, 95% CI 1.0–1.2).
This study found that recency of HIV-1 infection and the development of DM tropism may be associated with HAND in the relatively early stage of infection. Together these data suggest that viral interaction with cellular receptors may play an important role in the early manifestation of HAND.
HIV-associated neurocognitive disorders; coreceptor tropism; methamphetamine
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.
Episodic memory; Aging; Neuropsychological assessment; AIDS dementia complex; Cognition