Imaging the translocator protein 18 kDa within cognitive control and declarative memory circuits in virally-suppressed people with HIV.

Objectives: Virally-suppressed people with HIV (VS-PWH) show heterogeneity in patterns of cognitive dysfunction. To better understand the relationship between the neuroimmune response and cognition, we used positron emission tomography (PET) to image the translocator protein 18 kDa (TSPO). The study examined HIV-serostatus differences in TSPO as well as associations between regional TSPO and select cognitive processes defined using the Research Domain Criteria (RDoC) framework.

Altered development and network connectivity in a human neuronal model of 15q11.2 deletion-related neurodevelopmental disorders.

The chromosome 15q11.2 locus is deleted in 1.5% of patients with genetic epilepsy and confers a risk for intellectual disability and schizophrenia.

Intact HIV reservoir in monocytes is associated with cognitive function in virally suppressed women with HIV.

Background: Monocytes are susceptible to HIV infection, form HIV reservoirs, and contribute to central nervous system complications (e.g., cognitive impairment) in virally suppressed women with HIV(vsWWH).

Emotional Loneliness Is Related to Objective Cognitive Function in Older People With HIV in the Washington-Baltimore Area: A Cross-sectional Study.

Loneliness confers a significant risk to numerous health outcomes, including cognitive impairment. This study assessed the relationship between loneliness subtypes (social and emotional) and cognition in older people with HIV (OPWH ≥ 50 years). Forty-two participants (STET = 61.

Biopsychosocial phenotypes in people with HIV in the CHARTER cohort.

Neuropsychiatric complications such as neurocognitive impairment and depression are common in people with HIV despite viral suppression on antiretroviral therapy, but these conditions are heterogeneous in their clinical presentations and associated disability. Identifying novel biopsychosocial phenotypes that account for neurocognitive performance and depressive and functional symptoms will better reflect the complexities encountered in clinical practice and may have pathological and therapeutic implications. We classified 1580 people with HIV based on 17 features, including 7 cognitive domains, 4 subscales of the Beck depression inventory-II, 5 components of the patient's assessment of own functioning inventory, and dependence in instrumental and basic activities of daily living.

Tryptophan-Kynurenine Pathway Activation and Cognition in Virally Suppressed Women With HIV.

Background: Immune and cognitive dysfunction persists even in virally suppressed women with HIV (VS-WWH). Since inflammation and HIV proteins induce the enzyme indoleamine 2,3-dioxygenase (IDO), converting tryptophan (T) to kynurenine (K) while producing downstream neurotoxic metabolites, we investigated IDO activation (KT ratio) in relation to cognition in VS-WWH and demographically similar women without HIV (WWoH).

Methods: Ninety-nine VS-WWH on stable antiretroviral therapy and 102 WWoH (median age 52 vs 54 years; 73% vs 74% Black, respectively) from the New York and Chicago sites of the Women's Interagency HIV Study (WIHS) completed a neuropsychological test battery assessing motor function, processing speed, attention/working memory, verbal fluency, verbal learning and memory, and executive function and had plasma measured for tryptophan-kynurenine metabolites through liquid chromatography-tandem mass spectrometry and monocyte-derived [soluble cluster of differentiation-14 (sCD14), soluble cluster of differentiation-163 (sCD163), monocyte chemoattractant protein-1 (MCP-1)] plus general inflammatory markers [tumor necrosis factor alpha-2 receptor (TNF-R2), high-sensitivity C-reactive protein, high-sensitivity interleukin-6] through enzyme-linked immunosorbent assays between 2017 and 2020.

Phase-amplitude coupling detection and analysis of human 2-dimensional neural cultures in multi-well microelectrode array in vitro.

Background: Human induced pluripotent stem cell (hiPSC)- derived neurons offer the possibility of studying human-specific neuronal behaviors in physiologic and pathologic states in vitro. It is unclear whether cultured neurons can achieve the fundamental network behaviors required to process information in the brain. Investigating neuronal oscillations and their interactions, as occurs in cross-frequency coupling (CFC), addresses this question.

Tryptophan-kynurenine metabolic pathway and daytime dysfunction in women with HIV.

Sleep disturbances are prevalent in women with HIV (WWH). Tryptophan-kynurenine (T-K) pathway metabolites are associated with alterations in actigraphy derived sleep measures in WWH, although may not always correlate with functional impairment. We investigated the relationship between T-K pathway metabolites and self-reported daytime dysfunction in WWH and women without HIV (WWoH).

Brain N -acetyl-aspartyl-glutamate is associated with cognitive function in older virally suppressed people with HIV.

Objectives: Cognitive impairment persists in virally suppressed people with HIV (VS-PWH) especially in higher order domains. One cortical circuit, linked to these domains, is regulated by N -acetyl-aspartyl glutamate (NAAG), the endogenous agonist of the metabotropic glutamate receptor 3. The enzyme glutamate carboxypeptidase II (GCPII) catabolizes NAAG and is upregulated in aging and disease.

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 ( = 43.

Pilot imaging of the colony stimulating factor 1 receptor in the brains of virally-suppressed individuals with HIV.

Objective: Neuroimmune activation is a putative driver of cognitive impairment in people with HIV (PWH), even in the age of modern antiretroviral therapy. Nevertheless, imaging of the microglial marker, the 18 kDa translocator protein (TSPO), with positron emission tomography (PET) in treated PWH has yielded inconclusive findings. One potential reason for the varied TSPO results is a lack of cell-type specificity of the TSPO target.

Trauma Across the Life Span and Multisystem Morbidity in Women With HIV.

Objective: Sexual and physical abuse are highly prevalent among women living with HIV (WLWH) and are risk factors for the development of mental health and substance use disorders (MHDs, SUDs), and cognitive and medical comorbidities. We examined empirically derived patterns of trauma, MHD, and SUD, and associations with later cognitive and health outcomes.

Methods: A total of 1027 WLWH (average age = 48.

Machine Learning Approaches to Understand Cognitive Phenotypes in People With HIV.

Cognitive disorders are prevalent in people with HIV (PWH) despite antiretroviral therapy. Given the heterogeneity of cognitive disorders in PWH in the current era and evidence that these disorders have different etiologies and risk factors, scientific rationale is growing for using data-driven models to identify biologically defined subtypes (biotypes) of these disorders. Here, we discuss the state of science using machine learning to understand cognitive phenotypes in PWH and their associated comorbidities, biological mechanisms, and risk factors.

Tumor-derived extracellular vesicles modulate innate immune responses to affect tumor progression.

Immune cells are capable of influencing tumor progression in the tumor microenvironment (TME). Meanwhile, one mechanism by which tumor modulate immune cells function is through extracellular vesicles (EVs), which are cell-derived extracellular membrane vesicles. EVs can act as mediators of intercellular communication and can deliver nucleic acids, proteins, lipids, and other signaling molecules between cells.

Cx43 hemichannels contribute to astrocyte-mediated toxicity in sporadic and familial ALS.

Connexin 43 (Cx43) gap junctions and hemichannels mediate astrocyte intercellular communication in the central nervous system under normal conditions and contribute to astrocyte-mediated neurotoxicity in amyotrophic lateral sclerosis (ALS). Here, we show that astrocyte-specific knockout of Cx43 in a mouse model of ALS slows disease progression both spatially and temporally, provides motor neuron (MN) protection, and improves survival. In addition, Cx43 expression is up-regulated in human postmortem tissue and cerebrospinal fluid from ALS patients.

Integrase Inhibitors are Associated with Neuropsychiatric Symptoms in Women with HIV.

Women with HIV(WWH) are more likely to discontinue/change antiretroviral therapy(ART) due to side effects including neuropsychiatric symptoms. Efavirenz and integrase strand transfer inhibitors(INSTIs) are particularly concerning. We focused on these ART agents and neuropsychiatric symptoms in previously developed subgroups of WWH that differed on key sociodemographic factors as well as longitudinal behavioral and clinical profiles.

Plasma microRNAs are associated with domain-specific cognitive function in people with HIV.

Objective: Cognitive impairment remains common in people with HIV (PWH) on antiretroviral therapy (ART). The clinical presentation and severity are highly variable in PWH suggesting that the pathophysiological mechanisms of cognitive complications are likely complex and multifactorial. MicroRNA (miRNA) expression changes may be linked to cognition as they are gene regulators involved in immune and stress responses as well as the development, plasticity, and differentiation of neurons.

Dietary intake is associated with neuropsychological impairment in women with HIV.

Background: Diet is a modifiable risk factor that may influence cognition in people with HIV.

Objectives: We examined the association between dietary intake and cognition in women with HIV (WWH) and HIV-seronegative women.

Methods: An 18-item dietary National Cancer Institute screener was completed by 729 WWH and 346 HIV-seronegative Women's Interagency HIV Study participants.

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.

Integrase Strand Transfer Inhibitor Start or Switch Impacts Learning in Women With HIV.

Background: Integrase strand transfer inhibitors (INSTIs) are first-line regimens for HIV treatment. We aimed to examine their impact on cognitive performance and depressive symptoms in women with HIV (WWH).

Setting: Women's Interagency HIV Study, a multisite, prospective, cohort study.