1a) Genetic and Environmental Factors That May Influence HIV Dementia
HIV-associated dementia (HAD) is also referred to as HIV-associated neurocognitive disorder (HAND). Even though there are numerous neurologic diseases associated with genetics, the HAND is not heritable. Hence, there are no heritable neuropsychiatric symptom or neurocognitive deficits for use in exploring the disease etiology. Nonetheless, variation in genes related to numerous biological processes that could immensely impact antiretroviral (ARV) medication, disease course, and neurocognitive impairment.
There are numerous immune factors that implicate chronic neuroinflammatory, which result in HAND with respect to cell surface receptors, chemokine's and cytokines (Levine, Panos, & Horvath, 2015). Chemokine's and cytokines genes could influence HAND. Since HIV needs co-receptor in order to enter into cells, chemokine is bound to compete with HIV for these receptors with disease progression and modified HIV replication. Moreover, chemokine affects chemotaxis and macrophage activation in monocytes and other cells found at the blood-brain barrier (BBB) within the brain. These competitions result in increased viral seeding and inflammation of CNS. Additionally, chemokine may also alter neuronal signaling by disturbing neuronal and glial functions.
Moreover, research determines that monocyte chemoattractant protein-1 (MCP-1), recruit monocytes alongside other immune cells to CNS, which is partly responsible for a neuroinflammatory response. HIV infection within the leukocyte causes an increase in transmigrations across BBB to respond to MCP-1 (Levine, Panos & Horvath, 2015). Increase in transmigration directly result in MCP-1. Moreover, HIV protein called Nef also induces MCP-1 expression. The analysis determines that there are high levels of the MCP-1 result in HAND.
Additionally, Macrophage inflammatory protein 1-alpha (MIP-1a) or CCL3, which is a group of chemokine also influence the development of HAND (Levine, Panos, & Horvath, 2015). MIP-1a is another type of chemokine that acts as a natural ligand for CCR5 HIV co-receptors. MIP-1a is normally released by astrocytes and microglia. Its amount is higher in patients with HIVE. With the progression of HIV, SNP (rs1130371) formation in the MIP-1a immensely attributed to risks in HAD. Additionally, the interaction effect of HIV status and SNP (rs171934) reduces learning ability with time. The two markers of rs1719134 and rs1130371 are associated with disequilibrium within the brain.
Moreover, Mannose-binding lectin -2 (MBL -2) normally function by generating an innate immune response in bodies. Hence, its lower concentration in persons is associated with susceptibility to infections and quicker disease progression. Furthermore, mutation of the MBL- 2 genes at rs1800450, 1800451 or rs5030737, which are also referred to as B, C, and Dalles respectively result in a declined cognitive functioning. Research based on Chinese persons that are HIV+ indicated a neurocognitive decline in persons with MBL-2 mutations.
Apolipoprotein E (ApoE) gene normally helps in mediating innate immune response even though it primarily functions as a catabolism in triglyceride-rich lipoprotein (Levine, Panos & Horvath, 2015). ApoE e4 allele, with is associated with the pathogenesis of Alzheimer's disease is also associated with HAND. Nonetheless, there are inconsistencies in findings to ascertain this genetic contribution to HAND.
Environmental stress and HIV infections separately result in a decrease in cognitive functioning. Hence, there are stronger relationships in the two functions. A research was conducted to compare high environmental risk and lower environmental risks by examining their respective CD4+ in laboratory and IQ score psychological evaluation (Hochhauser, et al., 2008). In elevated risk environments, there is a higher correlation between CD4 and IQ. Hence, patients had higher IQ that has an association with gp120 levels, which is particularly immunocompromising since it exposes cortex and hippocampus to particular toxicity. Nonetheless, there is no relationship between IQ and CD4 for low environmental risk patients. b.) Brain Abnormalities Associated With HAND
Tumor necrosis factor - alpha (TNF-a) is normally linked to HAND (Levine, Panos, & Horvath, 2015). TNF- a refers to an inflammatory cytokine, which is produced by microglia and macrophages during viral replication, apoptosis, and immune cells regulation. HAD patients have higher amounts of TNF- a mRNA. There is numerous effect of TNF- a in the brains, which include glutamate neurotoxicity potentiation astrocytes ionic transfer disruption and cortical neurons. Additionally, it results in increased permeability of BBB and oligodendrocytes damage that are part of brain abnormalities associated with HAND. Availability of SNP at TNF-a gene (rs1800629) promoter region is normally as a result of responding to the viral protein. Availability of as little as one allele having SNP was present in HAND condition and lacked in HIV+ persons without dementia and control group of healthy people.
Moreover, the presence of stromal cell-derived factor - 1 (SDF -1), which is known as CXC Chemokine Ligand 12/CXCL12 is a brain abnormality associated with HAND (Levine, Panos, & Horvath, 2015). HIV co-receptor CXCR4 normally inhabits HIV-1 transmission through a tight competition for CXCR4 binding. Such actions are enabled through increased expression of HIV co-receptor CXCR4 within the rectal and genital epithelium. Moreover, SDF -1 reduces the expression of CXCR4 and hence hindering infections of T-tropic HIV-1 strain. Studies determine that higher levels of SDF-1 mRNA are present in HIVE persons when compared to healthy control group. Hence, when a person is infected with HIV virus, this chemokine has an immense association with HAND. Since SDF-1 has toxic properties, their accumulation affects brain neurons.
The Modified HIV Dementia Scale is the most efficient tool for screening cognitive impairment in HIV-dementias. Through a series of the trial on multiple populations, the result is deemed valid with accurate repeatability on evaluating dementia. More recent studies indicate that Montreal Cognitive Assessment or Montreal Assessment Scale as a more advantageous tool for measuring cognitive domain through multiple evaluations in a given setting (Watkins, & Treisman, 2015).
MRI and CT scan are essential for detecting changes in the brain in order to support the diagnosis of HAND. Researchers indicate that brain changes worsen with time in persons with HAND. MRI and CT scan provide a 3-dimensional image, which in this case shows brain atrophy or shrinkage.
C) Legal, Forensic and Ethical Issues Associated With HAND
Provisions in the 2008 Mental Health Parity and Addiction Equity Act (MHPAEA) compel insurers to offer equal benefits for mental health treatment like other physical treatments. In 2010, Obama's Administration made insurer cover mental health as part of their requirements. Nonetheless, issues regarding limited parity cause the cover to vary in its services because of limited financial resources across different states. Additionally, care duration in insurance also results in the varied implementation of this law by a different institution. Minimum benefits requirements are also applicable to this law even though they are not specifically included in its mandates. Therefore different insurance companies have different benefit cover that limits their application in the available treatment facilities. There are needs for patients to seek for guidance on what benefits are under their cover with the aim of seeking for a suitable hospital for appropriate medication as per the cover (Foundations recovery network, 2018).
Additionally, provisions in the Fair Housing Act prohibit organization against discriminating persons with disabilities for housing needs. Through this law, persons with HAND obtain protection against denial from rights of life activities that are of public importance. The term disability inscribes persons with mental and physical impairments including persons with HIV infections, mental illness, and mental retardation. Life activities include performing manual tasks, working, learning and having self-care. Nonetheless, does not apply to persons incarcerated for one reason or another since they pose direct threats to people and their property. The law especially concentrates on issues related to land to ensure reduced restriction to residential arrangements, restricting communal or congregation interactions. Secondly, involves the construction of multifamily housing that persons with wheels could easily access. Nonetheless, due to lack of enough finances, some houses lack facility that enhances access by persons in wheels (USDJ, 2017).
2.) Interview, Tests, and Assessments for HAND
a.) Screening Tools
The most common screening tool used for the HAND is HIV Dementia Scale (HDS) because it provides rapid assessment of motor skills, attention, simple learning, and movements. Additionally, HDS has acceptable sensitivity for assessing advanced cases of HAND. When using HDS, its cut point is 10 over 16 and has about 0.92 measurements and specificity of 0.71 in terms of accuracy (Valcour, et al., 2011). Since Mr. G impairment is not very severe; expected values for specificity and sensitivity after screening Mr. G can record figures like 85% and 39% respectively.
c) Assessing Cognitive Speed
Normative data attained from Trial Making Test (TMT) A and B is normally used for assessing HAND in adults between the ages of 18 years and above. MTM A&B determines numerous cognitive functioning that includes speed of processing, visual search, executive functions, scanning and mental flexibility. The value of TMT decreases with increased dementia cases. Findings from the test help neuropsychologist in determining the degree to which scores correlate with impairment performance in the patient (Tombaugh, 2018). The test is two parts; the first part TMT-A involves drawing a sequential line to connect 25 encircled numbers, which are usually distributed on a piece of paper. The second part of the test involves TMT-B where persons are tasked with alternating numbers and letters. Scores are obtained in regards to time taken to finish the task. The expected value of trial MTM-A may take 40 minutes and MTM-B may take 70 minutes when testing Mr. G.
d.) Assessment of Two and Three Dimensional Constructional Ability Using WAIS Battery
Assessment of two and three dimensional constructional by WAIS battery involves visuoconstructive and visuospatial abilities for comprehending dimensionality and pattern recognition (Johansson, & Wahlin, 1998). The test involves reading and telling time and setting certain time on clock face. Additionally, it involves reading and drawing maps with the aim of representing ecological examples by cognitive domain. Assessment of Mr. G by the use of WAIS battery test will have moderate performance because of HAND conditions.
e.) Assessing Verbal and Spatial Memory
Assessing verbal and spatial memory using Rey Osterreith Complex Figure assess the stability of cognitive domain based on neuropsychological battery (Livelli, et al., 2015). The test comprises of 22 tests and can cover 8 cognitive domains with regards to the patient's needs. When assessing Mr. G there were slight impairments of executive functioning, memory, and verbal fluency.
f.) Assessing Verbal Fluency
Semantic and episodic memory can be assessed by the use of Verbal Fluency Tests, the Boston Naming Test and California Verbal Learning Test. Since HAD is commonly related to subcortical brain dysfunction, the test helps in ascertaining the condition (White, et al., 1997).
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