Identifying and distinguishing cognitive profiles among virally suppressed people with HIV.

OBJECTIVE: Cognitive deficits are common among people with HIV (PWH), even when virally suppressed. We identified cognitive profiles among virally suppressed PWH and determined how sociodemographic, clinical/behavioral, and HIV disease characteristics distinguish profile membership. METHOD: Participants included 704 virally suppressed PWH (Mage = 43.9 [SD = 10.2], 88% male, 58.9% non-Hispanic White) from the HIV Neurobehavioral Research Program. Demographically adjusted T scores were derived from a neuropsychological evaluation comprised of 13 tests. We implemented a pipeline involving dimension reduction and clustering to identify profiles of cognitive performance. Random forest models on a 70/30 training/testing set with internal cross-validation were used to identify sociodemographic, clinical/behavioral, and HIV disease correlates of profile membership. RESULTS: Six cognitive profiles were identified: (a) "unimpaired" (19.9%); (b) weakness in verbal learning and memory (15.5%); (c) weakness in executive function and learning (25.8%); (d) weakness in motor, processing speed, and executive function (8.1%); (e) impaired learning and recall with weak-to-impaired motor, processing speed, and executive function (13.1%); (f) global deficits (17.6%). The most discriminative sociodemographic, clinical/behavioral, and HIV disease characteristics varied by profile with self-reported mood symptoms and cognitive/functional difficulties (e.g., language/communication, memory, and overall everyday function complaints) most consistently associated with profile membership. CONCLUSIONS: Cognitive profiles and their associated factors among PWH are heterogeneous, but learning/memory deficits were most common and self-reported mood, and cognitive/functional difficulties were most consistently related to profile membership. This heterogeneity in cognitive profiles and their correlates in PWH suggests that differing mechanisms contribute to cognitive deficits and, thus, underscores the need for personalized risk reduction and therapeutic strategies among PWH. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Within-Person Test Score Distributions: How Typical Is "Normal"?

We evaluated within-person variability across a cognitive test battery by analyzing the shape of the distribution of each individual's scores within a battery of tests. We hypothesized that most healthy adults would produce test scores that are normally distributed around their own personal battery-wide, within-person (wp) mean. Using cross-sectional data from 327 neurologically healthy adults, we computed each person's mean, standard deviation, skew, and kurtosis for 30 neuropsychological measures. Raw scores were converted to T-scores using three degrees of calibration: (a) none, (b) age, and (c) age, sex, race, education, and estimated premorbid IQ. Regardless of calibration, no participant showed abnormal within-person skew (wpskew) and only 10 (3.1%) to 16 (4.9%) showed wpkurtosis greater than 2. If replicated in other samples and measures, these findings could illuminate how healthy individuals are endowed with different cognitive abilities and provide the foundation for a new method of inference in clinical neuropsychology.

Do "effort tests" really test effort?

OBJECTIVE: Little is known about how much effort to do well most people exert on cognitive testing. Here, we describe an experimental paradigm to manipulate and measure cognitive effort. METHOD: After baseline cognitive and performance validity testing (PVT), 38 participants were assigned to a standard (SI) or enhanced (EI) incentive condition. On retesting a week later, EI participants were told that they would receive a financial bonus whose amount depended on how much their retest performance improved over baseline. SI participants were told to do their best and promised a chance-based bonus. RESULTS: Larger improvements on retesting were assumed to reflect less effort at baseline. After calculating differences from baseline to follow-up, we compared the EI and SI groups using multivariate analysis of variance. We sought to identify predictors of lower cognitive effort at baseline by correlating change z scores with baseline PVT performance and other hypothesized markers of low cognitive effort. As hypothesized, the EI group showed larger improvements, including improvements on more cognitive tests, and were rated as and reported trying harder at retesting than the SI group. Standard PVT measures did not correlate with low baseline effort; however, resting one's head or slouching during cognitive testing signified low baseline cognitive effort. CONCLUSIONS: This study provides preliminary support for an experimental paradigm to manipulate and investigate cognitive effort, which still remains poorly understood. While PVTs can detect feigned cognitive impairment, they lack the sensitivity to detect low cognitive effort in persons who pass conventional PVT cutoffs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Patterns and Predictors of Cognitive Function Among Virally Suppressed Women With HIV.

Cognitive impairment remains frequent and heterogeneous in presentation and severity among virally suppressed (VS) women with HIV (WWH). We identified cognitive profiles among 929 VS-WWH and 717 HIV-uninfected women from 11 Women's Interagency HIV Study sites at their first neuropsychological (NP) test battery completion comprised of: Hopkins Verbal Learning Test-Revised, Trail Making, Symbol Digit Modalities, Grooved Pegboard, Stroop, Letter/Animal Fluency, and Letter-Number Sequencing. Using 17 NP performance metrics (T-scores), we used Kohonen self-organizing maps to identify patterns of high-dimensional data by mapping participants to similar nodes based on T-scores and clustering those nodes. Among VS-WWH, nine clusters were identified (entropy = 0.990) with four having average T-scores ≥45 for all metrics and thus combined into an "unimpaired" profile (n = 311). Impaired profiles consisted of weaknesses in: (1) sequencing (Profile-1; n = 129), (2) speed (Profile-2; n = 144), (3) learning + recognition (Profile-3; n = 137), (4) learning + memory (Profile-4; n = 86), and (5) learning + processing speed + attention + executive function (Profile-5; n = 122). Sociodemographic, behavioral, and clinical variables differentiated profile membership using Random Forest models. The top 10 variables distinguishing the combined impaired vs. unimpaired profiles were: clinic site, age, education, race, illicit substance use, current and nadir CD4 count, duration of effective antiretrovirals, and protease inhibitor use. Additional variables differentiating each impaired from unimpaired profile included: depression, stress-symptoms, income (Profile-1); depression, employment (Profile 2); depression, integrase inhibitor (INSTI) use (Profile-3); employment, INSTI use, income, atazanavir use, non-ART medications with anticholinergic properties (Profile-4); and marijuana use (Profile-5). Findings highlight consideration of NP profile heterogeneity and potential modifiable factors contributing to impaired profiles.

Sex Differences in the Patterns and Predictors of Cognitive Function in HIV.

Despite advancements in antiretroviral therapy, mild cognitive deficits persist in nearly half of people with HIV (PWH). The profile of impairment in HIV is highly variable with deficits observed in a range of cognitive domains. Despite evidence of greater cognitive impairment among women with HIV (WWH) vs. men with HIV (MWH), it is unclear how MWH and WWH differ in the type of cognitive impairment and in risk factors associated with cognitive impairment profiles. In a large and well-characterized sample of PWH, we used machine learning to identify profiles of cognitive functioning and their associated factors overall and within sex. Participants included 1,666 PWH (201 WWH; 1,465 MMH) from the HIV Neurobehavioral Research Program who completed a neuropsychological test battery at their baseline visits. Using demographically-adjusted T-scores from 13 test outcomes assessing motor skills, executive functioning, attention/working memory, episodic learning and memory, verbal fluency, and processing speed, we used Kohonen self-organizing maps to identify patterns of high-dimensional data by mapping participants to similar nodes based on T-scores (MCLUST R package). Random forest models were used to determine how sociodemographic (e.g., age, education), clinical (e.g., depressive symptoms, substance use disorder), and biological (e.g., HIV disease characteristics) factors differentially related to membership within a cognitive profile. All analyses were repeated within sex. Three cognitive profiles were identified overall and within each sex. Overall and within MWH, there were unimpaired and global weakness profiles. The third profile in the total sample demonstrated relatively weak auditory attention whereas in MWH showed relative strengths in attention and processing speed. Conversely, there was no unimpaired profile among WWH. Rather, WWH demonstrated separate profiles reflecting weakness in motor skills, a relative weakness in learning and delayed recall, and global weaknesses with spared recognition memory. Despite different cognitive profiles by sex, the most discriminative factors were similar between men and women and included reading level (cognitive reserve), current and nadir CD4 count, plasma HIV viral load, duration of HIV disease, age, depressive symptoms, and race/ethnicity. Findings fill a knowledge gap concerning sex differences in cognitive impairment in PWH and inform personalized risk reduction and therapeutic strategies.

Prefrontal brain network connectivity indicates degree of both schizophrenia risk and cognitive dysfunction.

OBJECTIVE: Cognitive dysfunction is a core feature of schizophrenia, and persons at risk for schizophrenia may show subtle deficits in attention and working memory. In this study, we investigated the relationship between integrity of functional brain networks and performance in attention and working memory tasks as well as schizophrenia risk. METHODS: A total of 235 adults representing 3 levels of risk (102 outpatients with schizophrenia, 70 unaffected first-degree relatives of persons with schizophrenia, and 63 unrelated healthy controls [HCs]) completed resting-state functional magnetic resonance imaging and a battery of attention and working memory tasks (Brief Test of Attention, Hopkins Verbal Learning Test, and Brief Visuospatial Memory Test) on the same day. Functional networks were defined based on coupling with seeds in the dorsal anterior cingulate cortex, dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), and primary visual cortex. Networks were then dissected into regional clusters of connectivity that were used to generate individual interaction matrices representing functional connectivity within each network. RESULTS: Both patients with schizophrenia and their first-degree relatives showed cognitive dysfunction compared with HCs. First canonicals indicated an inverse relationship between cognitive performance and connectivity within the DLPFC and MPFC networks. Multivariate analysis of variance revealed multivariate main effects of higher schizophrenia risk status on increased connectivity within the DLPFC and MPFC networks. CONCLUSIONS: These data suggest that excessive connectivity within brain networks coupled to the DLPFC and MPFC, respectively, accompany cognitive deficits in persons at risk for schizophrenia. This might reflect compensatory reactions in neural systems required for cognitive processing of attention and working memory tasks to brain changes associated with schizophrenia.

Bupropion sustained release added to group support for smoking cessation in schizophrenia: a new randomized trial and a meta-analysis.

OBJECTIVE: To clarify the efficacy and tolerability of bupropion sustained release (SR) for the treatment of cigarette smoking in people with schizophrenia. METHOD: The first study is a double-blind, placebo-controlled clinical trial with 32 outpatients from the Maryland Psychiatric Research Center. From May 2003 to July 2007, clinically stable people with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who smoked at least 10 cigarettes per day and who were interested in quitting smoking or cutting down were recruited for participation. All participated in a 9-week support group and were randomly assigned to receive 12 weeks of bupropion SR or placebo. The primary outcome measure was 4 weeks' sustained abstinence over the last 4 study weeks. Secondary outcome measures included decrease in smoking behavior and change in symptoms, neuropsychological performance, and side effects. In the second study, we performed an electronic literature search of MEDLINE in September 2008. Articles in English published between 2003 and 2008 were searched for the terms schizophrenia, bupropion SR, and smoking. Bibliographies of studies identified through the MEDLINE search were also examined. Case reports, open-label studies, crossover studies, and studies using nonstandard dosing of bupropion SR were excluded. In this way, 4 studies similar in methodology to the currently presented clinical trial were identified and the individual data combined in a meta-analysis. A random effects meta-analysis using Comprehensive Meta-Analysis software was used to obtain a pooled estimate of the odds ratio for 4-week smoking abstinence between bupropion SR and placebo. RESULTS: There were no significant results on the primary or secondary smoking measures for the clinical trial, although a numeric advantage favored the bupropion SR group. There were no significant findings for secondary symptom or side effect measures and no significant change in neuropsychological performance. For the meta-analysis totaling 226 subjects, there were significant findings in favor of bupropion SR. The pooled estimate of the odds ratio for 4-week abstinence was 2.7 (95% CI, 1.3 to 5.7; P = .009), and clinically significant greater smoking reduction in the bupropion SR group, with pooled difference estimates increasing over time between groups, became statistically significant by week 5 of study medication (P < .02). CONCLUSIONS: New clinical trial data and a meta-analysis strongly support the tolerability and efficacy of bupropion SR for the treatment of cigarette smoking in people with schizophrenia TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00176449.