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Hiv associated neurocognitive disorder

Matthew V Green, Jonathan D Raybuck, Xinwen Zhang, Mariah M Wu, Stanley A Thayer
A defining feature of HIV-associated neurocognitive disorder (HAND) is the loss of excitatory synaptic connections. Synaptic changes that occur during exposure to HIV appear to result, in part, from a homeostatic scaling response. Here we discuss the mechanisms of these changes from the perspective that they might be part of a coping mechanism that reduces synapses to prevent excitotoxicity. In transgenic animals expressing the HIV proteins Tat or gp120, the loss of synaptic markers precedes changes in neuronal number...
March 14, 2018: Neurochemical Research
Summer J Rozzi, Valeria Avdoshina, Jerel A Fields, Italo Mocchetti
Human immunodeficiency virus-1 (HIV) infection of the central nervous system promotes neuronal injury that culminates in HIV-associated neurocognitive disorders. Viral proteins, including transactivator of transcription (Tat), have emerged as leading candidates to explain HIV-mediated neurotoxicity, though the mechanisms remain unclear. Tat transgenic mice or neurons exposed to Tat, which show neuronal loss, exhibit smaller mitochondria as compared to controls. To provide an experimental clue as to which mechanisms are used by Tat to promote changes in mitochondrial morphology, rat cortical neurons were exposed to Tat (100 nM) for various time points...
December 2018: Cell Death Discovery
Anas Z Abidin, Adora M DSouza, Mahesh B Nagarajan, Lu Wang, Xing Qiu, Giovanni Schifitto, Axel Wismüller
HIV is capable of invading the brain soon after seroconversion. This ultimately can lead to deficits in multiple cognitive domains commonly referred to as HIV-associated neurocognitive disorders (HAND). Clinical diagnosis of such deficits requires detailed neuropsychological assessment but clinical signs may be difficult to detect during asymptomatic injury of the central nervous system (CNS). Therefore neuroimaging biomarkers are of particular interest in HAND. In this study, we constructed brain connectivity profiles of 40 subjects (20 HIV positive subjects and 20 age-matched seronegative controls) using two different methods: a non-linear mutual connectivity analysis approach and a conventional method based on Pearson's correlation...
2018: NeuroImage: Clinical
Trena Mukherjee, Rishanantini Sakthivel, Ho Yen Fong, Megan McStea, Meng Li Chong, Sharifah Faridah Omar, Ai Vyrn Chin, Shahrul Kamaruzzaman, Adeeba Kamarulzaman, Reena Rajasuriar, Lucette A Cysique
This study determines the optimal cut-off scores for the Montreal Cognitive Assessment (MoCA) to detect HIV-associated neurocognitive disorders (HAND) in a multi-ethnic Malaysian HIV-positive cohort by developing demographically corrected normative standards among 283 HIV-negative community-based controls with overlapping demographic characteristics. The norms (corrected for age, sex, education, ethnicity) were applied to 342 HIV-positive virally suppressed individuals on cART. Impairment rates were classified using the Global Deficit Score (GDS ≥ ...
March 5, 2018: AIDS and Behavior
Norma Kabuba, J Anitha Menon, Donald R Franklin, Stian Lydersen, Robert K Heaton, Knut A Hestad
OBJECTIVE: Older age and lower education levels are known to be associated with worse neurocognitive (NC) performance in healthy adults, and individuals with HIV infection may experience accelerated brain/cognition aging. However, higher education may possibly protect against HIV-associated neurocognitive disorders (HAND). The aim of the current cross-sectional study was to assess the effect of age and education in an HIV-1 clade C infected adult population in urban Zambia. METHOD: Demographically corrected Zambian norms on a neuropsychological (NP) test battery were used to correct for normal age and education effects...
March 5, 2018: Neuropsychology
Luminita Ene
Introduction: Human immunodeficiency virus (HIV) enters the brain early, where it can persist, evolve, and become compartmentalized. Central nervous system (CNS) disease can be attributed to HIV alone or to the complex interplay between the virus and other neurotropic pathogens. Aim: The current review aims to describe the direct impact of HIV on the brain as well as its relationship with other pathogens from a practitioner's perspective, to provide a general clinical overview, brief workup, and, whenever possible, treatment guidance...
2018: Infectious Diseases
Teresa H Evering
PURPOSE OF REVIEW: The HIV-1 envelope gene (env) has been an intense focus of investigation in the search for genetic determinants of viral entry and persistence in the central nervous system (CNS). RECENT FINDINGS: Molecular signatures of CNS-derived HIV-1 env reflect the immune characteristics and cellular constraints of the CNS compartment. Although more readily found in those with advanced HIV-1 and HIV-associated neurocognitive disorders (HAND), molecular signatures distinguishing CNS-derived quasispecies can be identified early in HIV-1 infection, in the presence or absence of combination antiretroviral therapy (cART), and are dynamic...
February 19, 2018: Current HIV/AIDS Reports
M Mohamed, P B Barker, R L Skolasky, N Sacktor
BACKGROUND AND PURPOSE: Validated neuroimaging markers of HIV-associated neurocognitive disorder in patients on antiretroviral therapy are urgently needed for clinical trials. The purpose of this study was to explore the relationship between cognitive impairment and brain metabolism in older subjects with HIV infection. It was hypothesized that MR spectroscopy measurements related to neuronal health and function (particularly N -acetylaspartate and glutamate) would be lower in HIV-positive subjects with worse cognitive performance...
February 15, 2018: AJNR. American Journal of Neuroradiology
Kelly E Bowen, Stephen O Mathew, Kathleen Borgmann, Anuja Ghorpade, Porunelloor A Mathew
NK cells play important role in immunity against pathogens and cancer. NK cell functions are regulated by inhibitory and activating receptors binding corresponding ligands on the surface of target cells. NK cells were shown to be recruited to the CNS following several pathological conditions. NK cells could impact CNS physiology by killing glial cells and by secreting IFN-γ. Astrocytes are intimately involved in immunological and inflammatory events occurring in the CNS and reactive astrogliosis is a key feature in HIV-associated neurocognitive disorders...
2018: PloS One
Uraina S Clark, Miguel Arce Rentería, Rachal R Hegde, Susan Morgello
There is burgeoning evidence that, among HIV+ adults, exposure to high levels of early life stress (ELS) is associated with increased cognitive impairment as well as brain volume abnormalities and elevated neuropsychiatric symptoms. Currently, we have a limited understanding of the degree to which cognitive difficulties observed in HIV+ High-ELS samples reflect underlying neural abnormalities rather than increases in neuropsychiatric symptoms. Here, we utilized a behavioral marker of cognitive function, reaction time intra-individual variability (RT-IIV), which is sensitive to both brain volume reductions and neuropsychiatric symptoms, to elucidate the unique contributions of brain volume abnormalities and neuropsychiatric symptoms to cognitive difficulties in HIV+ High-ELS adults...
2018: Frontiers in Behavioral Neuroscience
Priyanka Verma, Ramesh V Asopa
Human immunodeficiency virus (HIV)-related dementia is the most severe form of neurocognitive disorder in patients with AIDS. It is relatively uncommon in postantiretroviral therapy (HAART) era and is associated with a high cerebrospinal fluid CSF/plasma viral load. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has proven useful in malignancies, infections, and central nervous system lesions in HIV-infected patients and has been used to explore regional cerebral glucose metabolism patterns in HIV-positive patients with and without cognitive impairment...
January 2018: Indian Journal of Nuclear Medicine: IJNM: the Official Journal of the Society of Nuclear Medicine, India
Natalie C Chen, Andrea T Partridge, Ferit Tuzer, Justin Cohen, Timothy Nacarelli, Sonia Navas-Martín, Christian Sell, Claudio Torres, Julio Martín-García
HIV-1 causes premature aging in chronically-infected patients. Despite effective anti-retroviral therapy, around 50% of patients suffer HIV-associated neurocognitive disorders (HAND), which likely potentiate aging-associated neurocognitive decline. Microglia support productive HIV-1 infection in the brain. Elevated markers of cellular senescence, including p53 and p21, have been detected in brain tissues from patients with HAND, but the potential for microglia senescence during HIV-1 infection has not been investigated...
February 5, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Martha Martínez-Banfi, Jorge I Vélez, M Victoria Perea, Ricardo García, Pedro J Puentes-Rozo, Moises Mebarak Chams, Valentina Ladera
Human immunodeficiency virus (HIV-1) infection and acquired immunodeficiency syndrome (AIDS) lead to neurocognitive disorders; however, there is still much knowledge to be gained regarding HIV-associated neurocognitive disorders. The purpose of this study was to assess the cognitive performance, instrumental activities of daily living, depression, and anxiety in patients with asymptomatic HIV-1 infections compared with seronegative participants without neurocognitive impairment. We studied a sample consisted of 60 patients with asymptomatic HIV-1 infections and 60 seronegative participants without neurocognitive impairment from the city of Barranquilla, Colombia, with a mean age of 36...
February 7, 2018: AIDS Care
Stephanie J Bissel, Kate Gurnsey, Hank P Jedema, Nicholas F Smith, Guoji Wang, Charles W Bradberry, Clayton A Wiley
BACKGROUND: Damage to the central nervous system during HIV infection can lead to variable neurobehavioral dysfunction termed HIV-associated neurocognitive disorders (HAND). There is no clear consensus regarding the neuropathological or cellular basis of HAND. We sought to study the potential contribution of aging to the pathogenesis of HAND. Aged (range = 14.7-24.8 year) rhesus macaques of Chinese origin (RM-Ch) (n = 23) were trained to perform cognitive tasks. Macaques were then divided into four groups to assess the impact of SIVmac251 infection (n = 12) and combined antiretroviral therapy (CART) (5 infected; 5 mock-infected) on the execution of these tasks...
February 1, 2018: Retrovirology
Alfonso Zamudio-Rodríguez, Pablo F Belaunzaran-Zamudio, Juan Sierra-Madero, Jennifer Margarita Cuellar-Rodríguez, Brenda Crabtree-Ramírez, Juan Luis Alcalá-Zermeno, Hélène Amieva, José Alberto Avila-Funes
INTRODUCTION: The population of aging adults living with Human Immunodeficiency Virus (HIV) is growing worldwide and evidence suggests that frailty occurs prematurely among them. In turn, frailty has been associated with cognitive decline. It is unknown, however, if people with both frailty and HIV-infection have higher risk of cognitive impairment compared with non-frail HIV-infected persons. Therefore, the main objective of this study was to determine the association between the phenotype of frailty and HIV-associated neurocognitive disorders (HAND) among adults aged 50 years or older living with HIV/AIDS...
February 1, 2018: AIDS Research and Human Retroviruses
Coral M Capó-Vélez, Bryan Morales-Vargas, Aurian García-González, José G Grajales-Reyes, Manuel Delgado-Vélez, Bismark Madera, Carlos A Báez-Pagán, Orestes Quesada, José A Lasalde-Dominicci
Currently, there are no specific therapies to treat HIV-1 associated neurocognitive disorders (HAND). The HIV-1 envelope, gp120, induces neuropathological changes similar to those in HAND patients; furthermore, it triggers an upregulation of the α7-nicotinic acetylcholine receptor (α7-nAChR), facilitating intracellular calcium overload and neuronal cell death. Using a gp120IIIB-transgenic mouse (gp120-tgm) model, we demonstrate that α7-nAChRs are upregulated on striatal neurons. Activation of α7-nAChRs leads to an increase in both intracellular calcium and percentage of apoptotic cells, which can be abrogated by antagonizing the receptor, suggesting a role for α7-nAChRs in gp120-induced neurotoxicity...
January 29, 2018: Scientific Reports
Masato Ogishi, Hiroshi Yotsuyanagi
BACKGROUND: HIV-associated neurocognitive disorder (HAND) remains an important and yet potentially underdiagnosed manifestation despite the fact that the modern combination antiretroviral therapy (cART) has achieved effective viral suppression and greatly reduced the incidence of life-threatening events. Although HIV neurotoxicity is thought to play a central role, the potential of viral genetic signature as diagnostic and/or prognostic biomarker has yet to be fully explored. RESULTS: Using a manually curated sequence metadataset (80 specimens, 2349 sequences), we demonstrated that only three genetic features are sufficient to predict HAND status regardless of sampling tissues; the accuracy reached 100 and 94% in the hold-out testing subdataset and the entire dataset, respectively...
January 27, 2018: Retrovirology
Stephen D Ginsberg, Melissa J Alldred, Satya M Gunnam, Consuelo Schiroli, Sang Han Lee, Susan Morgello, Tracy Fischer
OBJECTIVE: CD16+ /CD163+ macrophages (MΦs) and microglia accumulate in the brains of patients with human immunodeficiency virus (HIV) encephalitis (HIVE), a neuropathological correlate of the most severe form of HIV-associated neurocognitive disorders, HIV-associated dementia. Recently, we found that some parenchymal microglia in brain of HIV+ subjects without encephalitis (HIV/noE) but with varying degrees of neurocognitive impairment express CD16 and CD163, even in the absence of detectable virus production...
February 2018: Annals of Neurology
Qianwen Wang, Chun-Ho Wong, H Y Edwin Chan, Wai-Yip Lee, Zhong Zuo
DB213 is an HIV-1 replication inhibitor targeting the Central Nervous System for the treatment of HIV-associated neurocognitive disorders. Current study aims to develop an in situ thermosensitive gelling system for intranasal delivery of DB213 facilitated by statistical Design of Experiment (DoE) to conduct a more efficient experimentation by extracting the maximum amount of information from limited experiments. In our current study, information was extracted from twenty-five experimental designs from MODDE® Software and a mathematical model was successfully developed to predict formulations to achieve desired performance as well as to analyze relationships between the amount of Pluronic F-127, Pluronic F-68, Chitosan, DB213 and the performances of in situ thermosensitive gels...
January 20, 2018: International Journal of Pharmaceutics
Denise Cummins, Donna Waters, Christina Aggar, Catherine C O'Connor
AIM: To ascertain whether community-based health care providers were collecting appropriate information to identify patients at risk of HIV associated neurocognitive disorder and whether related documentation was complete. BACKGROUND: HIV associated neurocognitive disorder is a treatable neurological condition that can affect more than 20% of those infected with the HIV. Signs and symptoms of cognitive impairment may be subtle; therefore, documentation of medical and social information could be beneficial in identifying those at risk DESIGN: Cross sectional descriptive study...
January 24, 2018: Journal of Advanced Nursing
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