Age, cognitive status, and accuracy of ADL self-reports in adults living with HIV.

Determination of functional capacity in cognitively impaired persons living with HIV (PLHIV) is pivotal to the accurate diagnosis of HIV-associated neurocognitive disorders (HAND). Functional data is typically collected through self-report. Reliability concerns arise with memory and executive functioning impairments, which could compromise the integrity of self-report and result in inaccurate HAND diagnoses. The current study tested the accuracy of older PLHIV functional reports through examination of concordance rates between self-report and caregiver's (CG) report. Cross-sectional cognitive, mood, and functional status data were sampled from the Manhattan HIV Brain Bank. Participants and caregivers independently completed an Activities of Daily Living (ADL) questionnaire, producing 78 participant-caregiver dyads. Functional report concordance was operationalized by calculating differences between participant and CG ADL total scores. Assessment pairs differing by 2 or more points were considered to be discordant. Analyses revealed that one-third of the patient sample was discordant in the ADL report. ANOVA revealed that PLHIV overestimating their functional impairments, were significantly older, more educated, and more depressed than other participants. Global cognitive functioning was not associated with concordance. Thus, the majority of PLHIV were consistent with their caregivers' ADL report, and older age and increased depressive symptomatology, but not cognitive status, were factors associated with discordance.

Mild test anxiety influences neurocognitive performance among African Americans and European Americans: identifying interfering and facilitating sources.

The current study examined ethnic/racial differences in test-related anxiety and its relationship to neurocognitive performance in a community sample of African American (n = 40) and European American (n = 36) adults. The authors hypothesized the following: (a) Test-anxiety related to negative performance evaluation would be associated with lower neurocognitive performance, whereas anxiety unrelated to negative evaluation would be associated with higher neurocognitive performance. (b) African American participants would report higher levels of anxiety about negative performance evaluation than European Americans. (c) European Americans would report higher levels of anxiety unrelated to negative performance evaluation. The first two hypotheses were supported: Ethnic/racial differences in test-taking anxiety emerged such that African Americans reported significantly higher levels of negative performance evaluation, which was associated with lower cognitive performance. The third hypothesis was not supported: African Americans and European Americans reported similar levels of test-anxiety unrelated to negative evaluation.

HIV-related cognitive impairment shows bi-directional association with dopamine receptor DRD1 and DRD2 polymorphisms in substance-dependent and substance-independent populations.

It has been postulated that drugs of abuse act synergistically with HIV, leading to increased neurotoxicity and neurocognitive impairment. The CNS impacts of HIV and drug use converge on the mesocorticolimbic dopamine (DA) system, which contains two main receptor subtypes: dopamine receptors 1 (DRD1) and 2 (DRD2). DRD1 and DRD2 have been linked to substance dependence; whether they predict HIV-associated neurocognitive disorder (HAND) is unclear. Using an advanced-stage HIV+ population, we sought to determine if drug dependence impacts the contribution of DA receptor polymorphisms on neurocognition. We observed that both DRD1 and DRD2 polymorphisms were associated with opiate and cocaine dependence (P < 0.05) in Caucasian subjects, but not African-American individuals. Using linear regression analysis, we examined the polymorphisms for associations with neuropsychological performance in global and cognitive domain T-scores (Motor, Processing Speed, Verbal Fluency, Learning, Memory, Executive Functioning, Working Memory) while controlling for opiate and cocaine dependency. In the Motor domain, we observed an association for two DRD2 polymorphisms (P < 0.05) in Caucasian subjects. The effects differed for substance dependence groups as the direction of the correlations with DRD2 were opposite to what was seen in subjects without these dependencies. In African-American subjects, associations were observed in nearly every domain, and again, the direction of the correlation differed between substance-dependent and substance-independent groups. We conclude that studies to examine genetic risk for HAND must carefully account for substance dependence patterns when assaying dopaminergic systems, as the neurobiological substrates of cognition in HIV populations may vary with tonic alterations secondary to chronic substance exposures.

Major depressive disorder, cognitive symptoms, and neuropsychological performance among ethnically diverse HIV+ men and women.

Major depressive disorder (MDD), cognitive symptoms, and mild cognitive deficits commonly occur in HIV-infected individuals, despite highly active antiretroviral therapies. In this study, we compared neuropsychological performance and cognitive symptoms of 191 HIV-infected participants. Results indicated that participants with a formal diagnosis of current MDD performed significantly worse than participants without MDD in all seven neuropsychological domains evaluated, with the largest effect sizes in information processing speed, learning, and memory. In addition, a brief assessment of cognitive symptoms, derived from a comprehensive neuromedical interview, correlated significantly with neurocognitive functioning. Participants with MDD reported more cognitive symptoms and showed greater neurocognitive deficits than participants without MDD. These findings indicate that HIV-infected adults with MDD have more cognitive symptoms and worse neuropsychological performance than HIV-infected individuals without MDD. The results of this study have important implications for the diagnosis of HIV-associated neurocognitive disorders (HAND).

Isolating cognitive and neurologic HIV effects in substance-dependent, confounded cohorts: a pilot study.

Controversy exists as to whether effects of HIV infection can be detected in the cognitive profiles of substance users, with methodological differences in degree of control for confounding factors a major contributor to empirical discrepancies. To address this shortcoming, we conducted a small but well-controlled study aimed at isolating HIV neurocognitive (NC) effects in a group of chronic substance users. Thirty HIV-negative substance users were individually matched to 30 HIV-positive substance users on relevant medical and demographic factors, including reading level and methadone therapy status. Results revealed that reading level, methadone maintenance therapy, and positive urine toxicology each exerted significant influence on NC function, and that HIV status was a significant predictor of learning and speeded processing after these control factors were considered. The HIV-positive group also displayed significantly more neurologically assessed motor impairment (p < .05), which was specifically related to impaired cognition in this group and independent of degree of immunocompromise. These data demonstrate the need for increased attention to clinical/demographic characteristics of groups under study. They also show that with applied methodological rigor, the deleterious effects of HIV on cognition can be parsed from substance use, even in small samples with chronic and active use histories.

Effects of stereotype threat, perceived discrimination, and examiner race on neuropsychological performance: simple as black and white?

The purpose of the current study was to examine the predictive roles of stereotype threat and perceived discrimination and the mediating role of examiner-examinee racial discordance on neuropsychological performance in a non-clinical sample of African American and Caucasian individuals. Ninety-two African American (n = 45) and Caucasian (n = 47) adults were randomly assigned to either a stereotype threat or non-threat condition. Within each condition, participants were randomly assigned to either a same race or different race examiner. All participants underwent neuropsychological testing and completed a measure of perceived discrimination. African Americans in the stereotype threat condition performed significantly worse on global NP (Mz = -.30, 95% confidence interval [CI] [-0.07, -0.67] than African Americans in the non-threat condition (Mz = 0.09, CI [0.15, 0.33]. African Americans who reported high levels of perceived discrimination performed significantly worse on memory tests when tested by an examiner of a different race, Mz = -1.19, 95% CI [-1.78, -.54], than African Americans who were tested by an examiner of the same race, Mz = 0.24, 95% CI [-0.24, 0.72]. The current study underscores the importance of considering the role of contextual variables in neuropsychological performance, as these variables may obscure the validity of results among certain racial/ethnic groups.

Examining the role of participant and study partner report in widely-used classification approaches of mild cognitive impairment in demographically-diverse community dwelling individuals: results from the Einstein aging study.

Objective: The role of subjective cognitive concerns (SCC) as a diagnostic criterion for MCI remains uncertain and limits the development of a universally (or widely)-accepted MCI definition. The optimal MCI definition should define an at-risk state and accurately predict the development of incident dementia. Questions remain about operationalization of definitions of self- and informant-reported SCCs and their individual and joint associations with incident dementia. Methods: The present study included Einstein Aging Study participants who were non-Hispanic White or Black, free of dementia at enrollment, had follow-up, and completed neuropsychological tests and self-reported SCC at enrollment to determine MCI status. Informant-reported SCC at baseline were assessed via the CERAD clinical history questionnaire. Self-reported SCC were measured using the CERAD, items from the EAS Health Self-Assessment, and the single memory item from the Geriatric Depression Scale. Cox proportional hazards models examined the association of different operationalizations of SCC with Petersen and Jak/Bondi MCI definitions on the risk of dementia, further controlling for age, sex, education, and race/ethnicity. Time-dependent sensitivity and specificity at specific time points for each definition, and Youden's index were calculated as an accuracy measure. Cox proportional hazards models were also used to evaluate the associations of combinations of self- and informant-reported SCC with the risk of incident dementia. Results: 91% of the sample endorsed at least one SCC. Youden's index showed that not including SCC in either Jak/Bondi or Petersen classifications had the best balance between sensitivity and specificity across follow-up. A subset of individuals with informants, on average, had a lower proportion of non-Hispanic Blacks and 94% endorsed at least one self-reported SCC. Both informant-reported and self-reported SCC were significantly associated with incident dementia. Conclusion: Our findings suggest that the SCC criterion may not improve the predictive validity for dementia when included in widely-employed definitions of MCI. Consistent with some prior research, informant-reported SCC was more related to risk of incident dementia than self-reported SCC. Given that requiring informant report as a diagnostic criterion may unintentionally exclude health disparate groups, additional consideration is needed to determine how best to utilize informant-report in MCI diagnosis.

Distal sensory polyneuropathy is associated with neuropsychological test performance among persons with HIV.

While distal sensory polyneuropathy (DSP) is the most common neurological condition associated with HIV, causing nerve damage in upper and lower extremities, its impact on neuropsychological test performance is unclear. In this study, we analyzed baseline data for 278 HIV-infected participants with comprehensive neurological and neurocognitive evaluations to examine the contribution of DSP and anatomic distribution of neuropathic signs (upper extremity or lower extremity) on standardized domain scores. We found that participants with DSP performed significantly worse in multiple domains containing timed psychomotor tests (i.e., motor, information processing speed and executive functioning). With regard to executive functioning, differences were limited to a test with a motor component (Trail Making Test, Part B). The group with clinically detectable neuropathic signs in the upper extremities and the group with signs limited to the lower extremities both performed worse in the motor domain than the group without DSP. Participants with DSP demonstrated a unique pattern of impairment limited to neuropsychological domains with timed psychomotor tests. These results suggest that caution should be used in interpretation of neuropsychological tests in patients with DSP, as some abnormalities may be exacerbated by peripheral nervous system pathology. (JINS, 2012, 19, 1-10).

Official position of the American Academy of Clinical Neuropsychology on test security.

To provide education regarding the critical importance of test security for neuropsychological and psychological tests, and to establish recommendations for best practices for maintaining test security in forensic, clinical, teaching, and research settings. Previous test security guidelines were not adequately specified. METHOD: Neuropsychologists practicing in a broad range of settings collaborated to develop detailed and specific guidance regarding test security to best ensure continued viability of neuropsychological and psychological tests. Implications of failing to maintain test security for both the practice of neuropsychology and for society at large were identified. Types of test data that can be safely disclosed to nonpsychologists are described.Specific procedures can be followed that will minimize risk of invalidating future use of neuropsychological and psychological measures.Clinical neuropsychologists must commit to protecting sensitive neuropsychological and psychological test information from exposure to nonpsychologists, and now have specific recommendations that will guide that endeavor.

Ethnic/Racial Disparities in Longitudinal Neurocognitive Decline in People With HIV.

BACKGROUND: To examine longitudinal neurocognitive decline among Latino, non-Latino Black, and non-Latino White people with HIV (PWH) and factors that may explain ethnic/racial disparities in neurocognitive decline. METHODS: Four hundred ninety nine PWH (13.8% Latino, 42.7% Black, 43.5% White; baseline age: M = 43.5) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed neurocognitive, neuromedical, and laboratory assessments every 6-12 months with up to 5 years of follow-up. Longitudinal neurocognitive change was determined via published regression-based norms. Survival analyses investigated the relationship between ethnicity/race and neurocognitive change, and baseline and time-dependent variables that may explain ethnic/racial disparities in neurocognitive decline, including socio-demographic, HIV-disease, medical, psychiatric, and substance use characteristics. RESULTS: In Cox proportional hazard models, hazard ratios for neurocognitive decline were increased for Latino compared with White PWH (HR = 2.25, 95% CI = 1.35 to 3.73, P = 0.002), and Latino compared with Black PWH (HR = 1.86, 95% CI = 1.14 to 3.04, P = 0.013), with no significant differences between Black and White PWH (P = 0.40). Comorbidities, including cardiometabolic factors and more severe neurocognitive comorbidity classification, accounted for 33.6% of the excess hazard for Latino compared with White PWH, decreasing the hazard ratio associated with Latino ethnicity (HR = 1.83, 95% CI = 1.06 to 3.16, P = 0.03), but did not fully account for elevated risk of decline. CONCLUSIONS: Latino PWH may be at higher risk of early neurocognitive decline compared with Black and White PWH. Comorbidities accounted for some, but not all, of this increased risk among Latino PWH. Future research examining institutional, sociocultural, and biomedical factors, including structural discrimination and age-related biomarkers, may further explain the observed disparities.

Comment on Cory, 2021: White privilege in clinical neuropsychology: unpacking is not enough.

Byrd provided a response to the commentary by Cory on the role of White privilege in neuropsychology wherein an argument is introduced for the creation of a critical antiracist neuropsychology. In this brief reply, a discipline-specific context is introduced, and readers are encouraged to move beyond raised awareness of White privilege to commitment to dismantling the structures which support it.

The impact of sociocultural factors on prospective memory performance in HIV+ Latinx adults.

OBJECTIVE: Prospective memory (PM), a salient component of neurocognitive functioning for people living with HIV (PLH), is necessary for planning and coordinating health-related behaviors and instrumental tasks of daily living. However, little is known regarding the impact of sociocultural factors on PM in diverse populations, particularly Latinx PLH. The aim of this study was to examine ethnic group differences and sociocultural factors related to PM. METHOD: The sample of 127 PLH (91 Latinx and 36 non-Latinx white) completed measures of quality of education, socioeconomic status (SES), and a validated PM measure, the Memory for Intentions Screening Test (MIST). The Latinx group also completed a bicultural acculturation measure. RESULTS: Results revealed the Latinx and the non-Latinx white groups did not significantly differ in overall MIST performance (all p > .05). In the entire sample, better quality of education was associated with better MIST performance (all p < .05). Within the Latinx group, higher Latinx acculturation was associated with worse MIST performance (p = .02), whereas higher U.S. acculturation was associated with better MIST performance at a trend level (p = .07). Multivariate regressions revealed quality of education and Latinx acculturation significantly predicted MIST performance and PM errors (all p < .05). SES was not related to the MIST (all p > .10). CONCLUSIONS: In sum, clinicians must take sociocultural factors into consideration when working with Latinx PLH, as these factors influence cognitive functions (i.e., PM) vital to health-related behaviors. Integrating culturally-informed psychoeducation into care plans is an imperative first step. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Creating an antiracist psychology by addressing professional complicity in psychological assessment.

The acceptance of racist practices in psychological assessment, like the use of racist stimuli in testing material, has gone unchallenged for far too long. Such practices are emblematic of the entrenched systems of structural racism and pernicious presence of anti-Black oppression within psychology and beyond. This article brings into focus one glaring example: the inclusion of a noose as an item in one of the most widely used standardized tests in neuropsychology-the Boston Naming Test. The deeply offensive nature of this item has gone publicly unaddressed in the psychological literature for decades despite over 27,000 published articles with this test as a primary keyword. Herein, we review the history of the racialized weaponization of the noose in the United States; the potential psychological harm and test performance degradation imposed by including racist stimuli in assessment materials; and the ethical and cultural competency implications of exposing examinees to racist stimuli during psychological assessments. Finally, we call out the professional complicity underlying this item's persistence in psychology, urging psychologists, test publishers, and members of editorial boards to put an end to the complicit support and take clear corrective action in response to this offense. We also charge our colleagues and community to critically review other psychological assessment measures, language, and procedures in their respective subdisciplines to make the changes that will align professional practice with the antiracist values required to undo the effects of structural racism in psychology. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Cultural Neuropsychology Considerations in the Diagnosis of HIV-Associated Neurocognitive Disorders.

Human Immunodeficiency Virus Type-I (HIV) is a health disparities issue that affects culturally and linguistically diverse (CALD) and underrepresented minority populations to a greater degree than non-Hispanic white populations. Neurologically speaking, CALD populations experience worse HIV-related health outcomes, which are exacerbated by inadequate neurocognitive measures, poor normative samples, and the complex interplay of sociocultural factors that may affect test interpretation. Although cross-cultural neuropsychologists are working diligently to correct this gap in the literature, currently, studies examining neurocognitive outcomes among CALD populations are sparse. The most well-studied CALD groups are of African American/Black and Latinx adults in the US, and the chapter therefore focuses on these studies. There is more limited work among other populations in the US, such as Asians, Native Hawaiians, Pacific Islanders, and American Indians/Alaskan Natives, and even fewer studies for many CALD populations outside of the US. For example, HIV neuropsychology data is rare or nonexistent in the First Peoples of Australia and Indigenous People of Canada. It is often not adequately reported in Europe for the migrant populations within those countries or other world regions that have historically large multicultural populations (e.g., South America, Caribbean countries, Asia, and Africa). Therefore, this chapter reviews HIV-related health disparities faced by CALD populations with focus on North American research where it has been specifically studied, with particular attention given to disparities in HIV-Associated Neurocognitive Disorders (HAND). International data was also included for research with focus on First Peoples of Australia and Indigenous People of Canada. The chapter also examines other sociocultural and health factors, including global and regional (e.g., rural versus urban) considerations, migration, and gender. Further, guidelines for incorporating sociocultural consideration into assessment and interpretation of neurocognitive data and HAND diagnosis when working with HIV-positive CALD populations that would be relevant internationally are provided.

CCR2 on Peripheral Blood CD14+CD16+ Monocytes Correlates with Neuronal Damage, HIV-Associated Neurocognitive Disorders, and Peripheral HIV DNA: reseeding of CNS reservoirs?

HIV-associated neurocognitive disorders (HAND) occur in ~50% of HIV infected individuals despite combined antiretroviral therapy. Transmigration into the CNS of CD14+CD16+ monocytes, particularly those that are HIV infected and express increased surface chemokine receptor CCR2, contributes to neuroinflammation and HAND. To examine whether in HIV infected individuals CCR2 on CD14+CD16+ monocytes serves as a potential peripheral blood biomarker of HAND, we examined a cohort of 45 HIV infected people. We correlated CCR2 on CD14+CD16+ monocytes with cognitive status, proton magnetic resonance spectroscopy (1H-MRS) measured neurometabolite levels, and peripheral blood mononuclear cell (PBMC) HIV DNA copies. We determined that CCR2 was increased specifically on CD14+CD16+ monocytes from people with HAND (median [interquartile range (IQR)]) (63.3 [51.6, 79.0]), compared to those who were not cognitively impaired (38.8 [26.7, 56.4]) or those with neuropsychological impairment due to causes other than HIV (39.8 [30.2, 46.5]). CCR2 was associated with neuronal damage, based on the inverse correlation of CCR2 on CD14+CD16+ monocytes with total N-Acetyl Aspartate (tNAA)/total Creatine (tCr) (r2 = 0.348, p = 0.01) and Glutamine-Glutamate (Glx)/tCr (r2 = 0.356, p = 0.01) in the right and left caudate nucleus, respectively. CCR2 on CD14+CD16+ monocytes also correlated with PBMC HIV DNA copies (ρ = 0.618, p = 0.02) that has previously been associated with HAND. These findings suggest that CCR2 on CD14+CD16+ monocytes may be a peripheral blood biomarker of HAND, indicative of increased HIV infected CD14+CD16+ monocyte entry into the CNS that possibly increases the macrophage viral reservoir and contributes to HAND.

Measures of Physical and Mental Independence Among HIV-Positive Individuals: Impact of Substance Use Disorder.

With the transition of HIV infection from an acute to a chronic disease after the introduction of antiretroviral medications, there has been an increased focus on long-term neurocognitive and other functional outcomes of HIV patients. Thus, we assessed factors, particularly history of a substance use disorder, associated with time to loss of measures of physical or mental independence among HIV-positive individuals. Data were obtained from the National NeuroAIDS Tissue Consortium. Kaplan-Meier and Cox proportional hazards regression analyses were used to estimate the time since HIV diagnosis to loss of independence, and to identify associated risk factors. HIV-positive participants who self-identified as physically (n = 698) or mentally (n = 616) independent on selected activities of daily living at baseline were eligible for analyses. A history of substance use disorder was associated with a higher hazard of loss of both physical and mental independence [adjusted hazard ratio (HR) = 1.71, 95% confidence interval (95% CI): 1.07-2.78; adjusted HR = 1.67, 95% CI: 1.11-2.52, respectively]. After adjusting for substance use disorder and other covariates, older age at diagnosis and female gender were associated with higher hazards of loss of both physical and mental independence, non-white participants had higher hazards of loss of physical independence, whereas participants with an abnormal neurocognitive diagnosis and fewer years of education had higher hazards of loss of mental independence. In summary, history of substance use disorder was associated with loss of measures of both physical and mental independence. The nature of this link and the means to prevent such loss of independence need further investigation.

Reading Ability as an Estimator of Premorbid Intelligence: Does It Remain Stable Among Ethnically Diverse HIV+ Adults?

UNLABELLED: The Wide Range Achievement Test, 3rd edition, Reading Recognition subtest (WRAT-3 RR) is an established measure of premorbid ability. Furthermore, its long-term reliability is not well documented, particularly in diverse populations with CNS-relevant disease. OBJECTIVE: We examined test-retest reliability of the WRAT-3 RR over time in an HIV+ sample of predominantly racial/ethnic minority adults. METHOD: Participants (N = 88) completed a comprehensive neuropsychological battery, including the WRAT-3 RR, on at least two separate study visits. Intraclass correlation coefficients (ICCs) were computed using scores from baseline and follow-up assessments to determine the test-retest reliability of the WRAT-3 RR across racial/ethnic groups and changes in medical (immunological) and clinical (neurocognitive) factors. Additionally, Fisher's Z tests were used to determine the significance of the differences between ICCs. RESULTS: The average test-retest interval was 58.7 months (SD = 36.4). The overall WRAT-3 RR test-retest reliability was high (r = .97, p < .001) and remained robust across all demographic, medical, and clinical variables (all r's > .92). ICCs did not differ significantly between the subgroups tested (all Fisher's Z p's > .05). CONCLUSIONS: Overall, this study supports the appropriateness of word-reading tests, such as the WRAT-3 RR, for use as stable premorbid IQ estimates among ethnically diverse groups. Moreover, this study supports the reliability of this measure in the context of change in health and neurocognitive status and in lengthy inter-test intervals. These findings offer strong rationale for reading as a "hold" test, even in the presence of a chronic, variable disease such as HIV.

Psychological trauma exposure and co-morbid psychopathologies in HIV+Men and Women.

This study examined the association between trauma exposure, PTSD, suicide attempts, and other psychopathology among 316 racially/ethnically diverse HIV-infected men and women who underwent semi-structured psychiatric assessment. In addition, the role of psychological resilience in trauma exposure was examined in the context of neurological symptoms and functional status. Nearly half (47.8%; 151/316) of the participants reported trauma exposure, of which 47.0% (71/151) developed PTSD. Among trauma-exposed individuals, those with a current psychiatric diagnosis reported more neurological symptoms and lower functional status. Trauma exposure without PTSD was associated with a higher rate of panic disorder and substance-induced mental disorders. Trauma-exposed individuals who did not develop PTSD were less likely than those who reported no trauma exposure to meet criteria for major depressive disorder (MDD). Trauma exposure, MDD, borderline personality disorder, and substance-induced mental disorders were independently associated with increased odds of suicide attempt. These results indicate that co-morbid psychiatric disorders are common among trauma exposed individuals with a history of PTSD, but those with trauma exposure who do not develop PTSD are less likely to experience MDD. The role of other co-morbid psychopathologies in the genesis of suicidal behavior among individuals living with HIV deserves further study.

Effects of information processing speed on learning, memory, and executive functioning in people living with HIV/AIDS.

INTRODUCTION: It is unclear whether or to what degree literacy, aging, and other neurologic abnormalities relate to cognitive deficits among people living with HIV/AIDS in the combined antiretroviral therapy (CART) era. The primary aim of this study was to simultaneously examine the association of age, HIV-associated motor abnormalities, major depressive disorder, and reading level with information processing speed, learning, memory, and executive functions, and to determine whether processing speed mediated any of the relationships between cognitive and noncognitive variables. METHOD: Participants were 186 racially and ethnically diverse men and women living with HIV/AIDS who underwent comprehensive neurological, neuropsychological, and medical evaluations. Structural equation modeling was utilized to assess the extent to which information processing speed mediated the relationship between age, motor abnormalities, major depressive disorder, and reading level with other cognitive abilities. RESULTS: Age, motor dysfunction, reading level, and current major depressive disorder were all significantly associated with information processing speed. Information processing speed fully mediated the effects of age on learning, memory, and executive functioning and partially mediated the effect of major depressive disorder on learning and memory. The effect of motor dysfunction on learning and memory was fully mediated by processing speed. CONCLUSIONS: These findings provide support for information processing speed as a primary deficit, which may account, at least in part, for many of the other cognitive abnormalities recognized in complex HIV/AIDS populations. The association of age and information processing speed may account for HIV/aging synergies in the generation of CART-era cognitive abnormalities.