HIV Antiretroviral Medication Neuropenetrance and Neurocognitive Outcomes in HIV+ Adults: A Review of the Literature Examining the Central Nervous System Penetration Effectiveness Score

This literature review summarizes the existing research examining the CNS penetration effectiveness (CPE) score and neurocognitive outcomes (i.e., neuropsychological assessment and neurocognitive screening) in HIV+ individuals. Despite the effectiveness of Combined Antiretroviral Therapy (CART) in reducing mortality and morbidity in HIV and controlling viral replication, HIV often persists in the Central Nervous System (CNS), and rates of neurocognitive impairment remain higher than predicted in the post-CART era. The CPE score was developed to rank antiretroviral regimens on their ability to penetrate the CNS and potency in inhibiting the virus, and it has been examined in relation to neurocognitive functioning for over a decade. Based on the results of 23 studies, we conclude that CPE is not as strongly associated with neurocognitive outcomes as initially hypothesized, although higher CPE ARV regimens may be associated with modest, improved outcomes in global neurocognitive functioning, and to a lesser extent attention/working memory and learning/memory. Conclusions, however, are limited by the heterogeneity in study design and methods, and the lack of a more recent CPE metric update. It is recommended that future research in this area employ comprehensive, standardized neuropsychological test batteries and examine domain-level performance, and use the newer 2010 CPE metric, although an updated CPE ranking is urgently needed

Diversity in Alzheimer\u27s Disease Drug Trials: The Importance of Eligibility Criteria

INTRODUCTION: To generalize safety and efficacy findings, it is essential that diverse populations are well represented in Alzheimer\u27s disease (AD) drug trials. In this review, we aimed to investigate participant diversity in disease-modifying AD trials over time, and the frequencies of participant eligibility criteria. METHODS: A systematic review was performed using Medline, Embase, the Cochrane Library, and Clinicaltrials.gov, identifying 2247 records. RESULTS: In the 101 included AD trials, participants were predominantly White (median percentage: 94.7%, interquartile range: 81.0-96.7%); and this percentage showed no significant increase or decrease over time (2001-2019). Eligibility criteria such as exclusion of persons with psychiatric illness (78.2%), cardiovascular disease (71.3%) and cerebrovascular disease (68.3%), obligated caregiver attendance (80.2%), and specific Mini-Mental State Examination scores (90.1%; no significant increase/decrease over time) may have led to a disproportionate exclusion of ethnoracially diverse individuals. DISCUSSION: Ethnoracially diverse participants continue to be underrepresented in AD clinical trials. Several recommendations are provided to broaden eligibility criteria

HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors

Combination antiretroviral therapy (CART) has greatly reduced medical morbidity and mortality with HIV infection, but high rates of HIV-associated neurocognitive disorders (HAND) continue to be reported. Because large HIV-infected (HIV+) and uninfected (HIV−) groups have not been studied with similar methods in the pre-CART and CART eras, it is unclear whether CART has changed the prevalence, nature, and clinical correlates of HAND. We used comparable methods of subject screening and assessments to classify neurocognitive impairment (NCI) in large groups of HIV + and HIV − participants from the pre-CART era (1988–1995; N = 857) and CART era (2000–2007; N = 937). Impairment rate increased with successive disease stages (CDC stages A, B, and C) in both eras: 25%, 42%, and 52% in pre-CART era and 36%, 40%, and 45% in CART era. In the medically asymptomatic stage (CDC-A), NCI was significantly more common in the CART era. Low nadir CD4 predicted NCI in both eras, whereas degree of current immunosuppression, estimated duration of infection, and viral suppression in CSF (on treatment) were related to impairment only pre-CART. Pattern of NCI also differed: pre-CART had more impairment in motor skills, cognitive speed, and verbal fluency, whereas CART era involved more memory (learning) and executive function impairment. High rates of mild NCI persist at all stages of HIV infection, despite improved viral suppression and immune reconstitution with CART. The consistent association of NCI with nadir CD4 across eras suggests that earlier treatment to prevent severe immunosuppression may also help prevent HAND. Clinical trials targeting HAND prevention should specifically examine timing of ART initiation

An Essential Resource for Neuropsychological Evaluation of Hispanic/Latino Clients

Book Reviews: Principles of Neuropsychological Assessment With Hispanics: Theoretical Foundations and Clinical Practice, by Antolin M. Llorente (Ed.). 2008. New York: Springer for Science and Business Media, 234 pp., $59.95 (HB)

A biosystemic model of coping in schizophrenia

The behavioral effects of environmental stress on individuals with schizophrenia have been well documented in the literature. Such individuals are especially vulnerable to difficulties related to stress and possess limited coping skills to deal with psychosocial stressors. However, relatively little is known regarding the neuropsychological and neuroendocrinological substrates of coping in schizophrenia, and how they relate to the behavioral effects of stress within this population. The present study was designed to investigate the neuroendocrinological, neuropsychological, attributional, and behavioral mechanisms of coping within schizophrenia, and discuss implications for treatment. Study participants included a total of thirty-five individuals with the diagnosis of a schizophrenia-spectrum disorder as defined by the DSM-IV, and confirmed by a trained psychiatrist and licensed clinical psychologist. The results of this investigation revealed that Hypothalamus-Pituitary-Adrenal (HPA) axis dysregulation, (in the form of hypocortisolemia), neuropsychological impairments in executive functioning, and verbal learning and memory; and behavioral functioning all significantly predict coping attributions in schizophrenia. However, the relationship with HPA axis dysregulation and coping was marginal, while robust relationships were observed in the domains of neuropsychological and behavioral functioning with coping attributions. The results of this study generally support a priori hypotheses regarding the multi-systemic nature of coping in schizophrenia. With regard to treatment, it would be expected that pharmacological treatments (i.e., antipsychotics and cortisol regulating drugs) and psychosocial treatments (i.e., stress management and coping skills training) might all serve as useful strategies targeting HPA axis and behavioral dysregulation. Future empirical investigation must be undertaken in order to further elucidate these relationships with a larger sample, as well as systematically examine possible treatments to improve coping skills for stress within this population

Increasing culturally competent neuropsychological services for ethnic minority populations: A call to action

US demographic and sociopolitical shifts have resulted in a rapidly growing need for culturally competent neuropsychological services. However, clinical neuropsychology as a field has not kept pace with the needs of ethnic minority clients. In this discussion we review: historical precedents and the limits of universalism in neuropsychology; ethical/professional guidelines pertinent to neuropsychological practice with ethnic minority clients; critical cultural considerations in neuropsychology; current disparities germane to practice; and challenges to the provision of services to racial/ethnic minority clients. We provide a call to action for neuropsychologists and related organizations to advance multiculturalism and diversity within the field by increasing multicultural awareness and knowledge, multicultural education and training, multicultural neuropsychological research, and the provision of culturally competent neuropsychological services to racial/ethnic minority clients. Lastly, we discuss strategies for increasing the provision of culturally competent neuropsychological services, and offer several resources to meet these goals

Predictors of treatment utilisation at cognitive remediation groups for schizophrenia: The roles of neuropsychological, psychological and clinical variables.

The present study highlights the importance of carefully assessing neuropsychological functioning at the outset of cognitive remediation (CR) treatment. The effects of neuropsychological, psychological, and clinical variables on treatment utilisation (TU) in CR groups for individuals with schizophrenia were examined. Data included neuropsychological and psychosocial assessments conducted with 39 adult clients enrolled in CR as part of their ongoing outpatient therapy. TU was calculated using the percentage of sessions attended over a three-month period. Better global neuropsychological functioning (r = .46, p =.007), attention/working memory (r = .39, p = .03), and processing speed (r = .44, p = .01) were each associated with greater TU. Trend-level associations with TU were observed with executive functioning (r = .33, p = .06) and verbal learning (r = .23; p = .07). Higher rates of self-reported cognitive complaints were associated with lower TU (r = –.45, p = .01). Hierarchical regression analyses revealed that both objective and subjective indicators of neuropsychological functioning independently contributed to the prediction of TU. This information can serve to help providers develop empirically informed strategies to support their clients\u27 CR treatment utilisation. The implications from these findings can be used as a way to provide ongoing guidance for service provision and can aid in improving CR treatment utilisation, and thus treatment effectiveness, in clinical settings

Demographically corrected norms for the Brief Visuospatial MemoryTest-Revised and Hopkins Verbal Learning Test-Revised in Monolingual Spanish Speakers from the U.S. – Mexico Border Region

The large number of primary Spanish speakers both in the United States and the world makes it imperative that appropriate neuropsychological assessment instruments be available to serve the needs of these populations. In this article we describe the norming process for Spanish speakers from the U.S.–Mexico border region on the Brief Visuospatial Memory Test-revised and the Hopkins Verbal Learning Test-revised. We computed the rates of impairment that would be obtained by applying the original published norms for these tests to raw scores from the normative sample, and found substantial overestimates compared to expected rates. As expected, these overestimates were most salient at the lowest levels of education, given the under-representation of poorly educated subjects in the original normative samples. Results suggest that demographically corrected norms derived from a healthy Spanish-speaking adults with a broad range of education, are less likely to result in diagnostic errors. At minimum, demographic corrections for the tests in question should include the influence of literacy or education, in addition to the traditional adjustments for age. Because the age range of our sample was limited, the norms presented should not be applied to elderly populations