Neurocognitive Impairment and HIV PDF

Neuropsychology of HIV  Cognitive impairment among populations at risk for HIV poses a significant barrier to managing risk behaviors.  Literature suggests that cognitive impairment is intertwined in a close, reciprocal relationship with both risk behaviors and medication adherence.  Not...

Neuropsychology of HIV  Cognitive impairment among populations at risk for HIV poses a significant barrier to managing risk behaviors.  Literature suggests that cognitive impairment is intertwined in a close, reciprocal relationship with both risk behaviors and medication adherence.  Not only do increased risk behaviors and suboptimal adherence exacerbate cognitive impairment, but cognitive impairment also reduces the effectiveness of interventions aimed at optimizing medication adherence and reducing risk.  In order to be effective, risk-reduction interventions must therefore take into account the impact of cognitive impairment on learning and behavior. HIV-Associated Neurocognitive Impairment  While the prevalence of AIDS-associated dementia has declined dramatically since the advent of effective antiretroviral therapy (ART), less severe HIV- associated neurocognitive disorders remain common among people living with HIV.  HIV-associated neurocognitive disorder, or HAND, includes three levels of severity: ◦ Asymptomatic neurocognitive impairment: at least mild neuropsychological impairment in two or more domains but no decrease in everyday functioning;  Neurocognitive impairment can be defined as ‘asymptomatic’ because psychological tests of neurocognitive abilities including fine movement, memory, fluency and executive function (prioritisation and organisation) can detect substandard performances in one or more areas that are too subtle to be noticed by the person themselves or people who know them, or dismissed as everyday poor memory or clumsiness. ◦ Mild neurocognitive disorder: at least mild neuropsychological impairment in two or more domains with at least mildly decreased everyday functioning; ◦ HIV-associated dementia: overall neuropsychological impairment of at least moderate severity and major decline in everyday  In patients displaying symptoms of HAND, HIV has been found to specifically affect executive functions, episodic memory, information- processing speed, motor skills, attention/working memory, language, and sensory perception.  In a meta-analysis of HIV-related impairments, asymptomatic HIV-infected individuals were found to have the largest deficits in language and verbal functions, while individuals with symptomatic HIV and AIDS were found to have the greatest deficits in motor and executive functioning.  As HIV disease progresses, motor functioning, executive skills, and speed of information processing demonstrate the greatest decline.  Understanding the effects of HIV on the central nervous system is complicated by comorbid conditions that also affect cognitive function.  The onset of HIV-related neurological symptoms occurs when infected monocytes (white blood cells) and CD4 cells transport the virus across the blood–brain barrier within hours or days of initial infection. ◦ It has become an established fact that HIV-1 enters the brain after viral exposure leading to clinical dementia. ◦ The virus can cross the blood-brain barrier either during primary infection or at a later stage. Several of the neurocognitive deficits seen in patients with HAND have overt consequences for HIV risk behaviour. It is suggested that HAND can disrupt the brain structures responsible for impulse control HIV-related deficits in episodic memory are thought to be highly prevalent, impairing the ability to plan and execute intentions. Effects of Substance Abuse  Although injection drug use (IDU) has declined as an acquisition risk factor for new HIV infections, an estimated 22% of people living with HIV today were initially infected through IDU.  Drug use remains a common cofactor associated with HIV infection, and drug users are particularly at risk for underutilization of HIV care compared to other groups.  Chronic drug use itself is also strongly correlated with a host of neurocognitive impairments. Opioids  Opioids are a class of drugs that include the illegal drug heroin, synthetic opioids such as fentanyl, and pain relievers available legally by prescription  Individuals with opioid dependence and abuse demonstrate deficits in attention, working memory, episodic memory, and executive function during active use.  Moreover, deficits in complex working memory, executive function, and fluid intelligence persist into periods of early abstinence, while executive function impairments showed no signs of declining during abstinence.  Opioid dependence may also exacerbate HAND by reducing immune system integrity and stimulating viral replication.  When opioids were used in conjunction with cocaine, worsening neurocognitive function was observed in HIV infected individuals….. ◦ …..to the extent that practitioners have incorporated therapeutic techniques specifically designed to accommodate such impairments in HIV-infected opioid dependent patients. Cocaine  Like opioid dependence, chronic cocaine use exacerbates HIV replication; evidence also exists that cocaine increases the permeability of the blood–brain barrier to HIV and promotes cellular apoptosis(suicide or self-destruction).  Chronic cocaine users have impaired executive function, new learning, information-processing speed, memory, visuospatial perception, and attention, which may persist into abstinence.  Alcohol  Lifetime alcohol dependence has been found to impair attention, memory, and learning.  Although short-term memory and psychomotor skills were recovered after abstinence, impairments in long- term memory were found to persist for up to 7 years into sobriety.  In a study comparing HIV infected and HIV-uninfected subjects with a history of alcohol dependence, significant impairment was seen in the HIV-infected group in the cognitive domains of verbal reasoning, reaction time, and auditory processing, whereas no significant impairments were seen in the HIV- uninfected group.  This indicates that alcohol and HIV have combine and cause a greater effect on the central nervous system. Hepatitis C Coinfection  Hepatitis C viral infection (HCV), a blood-borne virus transmitted primarily through IDU and present in 55–90% of HIV-infected IDUs, may also have neuropsychological manifestations.  HCV can replicate in the central nervous system, resulting in cognitive deficits.  In one study, the effects of HCV and HIV infection were found to have additive effects on global cognitive impairment, learning, speed, problem solving, and recall tasks.  Moreover, some medications used for the treatment of chronic HCV infection, have been found to cause cognitive impairment. Traumatic Brain Injury  Few studies have focused on the contribution of brain injury to cognitive deficits in HIV-infected populations.  The available literature suggests that a history of brain injury contributes to poor neuropsychological performance among HIV-infected individuals, and that a high frequency of head trauma is present among HIV-infected individuals.  Individuals with HIV who have experienced head trauma reported a greater number of neuropsychological symptoms. Mental Illness  The disproportionate prevalence of HIV infection among adults with mental illness is well documented.  Substance use and psychiatric disorders are also highly prevalent in HIV infected individuals, and over 60% will suffer from one or both at some point during infection.  Among people with mental illness, alcohol users have been found to engage in riskier sexual behaviors compared to control subjects. Several studies have suggested that cognitive deficits associated with mental illness may exacerbate HAND or contribute to risk behaviours. Sexual Risk Behaviors  The Center for Disease Control and Prevention found that sexual transmission was an acquisition risk factor in 88% of new HIV infections, suggesting that managing sexual transmission of HIV is crucial to controlling transmission.  A number of studies have analysed the impact of risk factors for cognitive dysfunction (e.g. substance abuse and mental illness) on sexual risk-taking behaviors (e.g. unprotected sex and multiple partners).  In adolescents, major mental disorders increased sexual risk-taking behaviors compared to the general population, while a comorbid substance use disorder further increased the risk.  Impaired executive function inhibits rational decision-making by preventing the consideration of future outcomes in favor of current rewards and may prevent individuals from making safe sexual choices.  Slowed information processing or reaction time may prevent the timely, appropriate consideration of risk variables during decision-making.  Dysfunctional impulse control, which can result from the effects of HIV, substance abuse, or mental illness, may prevent individuals from executing safe sexual practices.  An important distinction must be made between cognitive function and the underlying personality traits that have long been thought to account for excessive risk behaviors, particularly “sensation seeking,” ◦ described as an inclination towards both novel experiences and risk-taking in order to achieve those experiences.  Two hypotheses have been made regarding the frequent co-occurrence of substance abuse and sexual risk behaviors: ◦ (1) that an underlying sensation-seeking personality is responsible for both; and ◦ (2) that other features of substance use, for instance, cognitive impairment, can account for increased risk behavior. Drug-Related Risk Behaviors  Because of impaired memory, executive function, and cognitive speed that result from both chronic substance use and HIV infection, cognitive impairment may directly influence drug related risk behaviors (e.g. sharing of needles).  Much of the research on the impact of cognitive function on HIV risk-taking, however, has focused on sexual, not drug related, behaviors.  The research findings were that young people who knew that HIV is transmitted through needle sharing were still inclined to share needles.  A more recent study explored the relationship between cognitive functioning, personal knowledge of someone who died of AIDS, and risk behaviors. ◦ The authors found that the effect of knowing someone who had died of AIDS was moderated by cognitive function:  Among those individuals who knew someone who had died of AIDS, those who demonstrated a lower cognitive function were more like to engage in high-risk injection behaviors (sharing drugs and injection equipment) than those who showed a higher cognitive function. ◦ The skills necessary to translate the understanding of HIV risk represented by knowing someone who died of AIDS into a reduction in risk behavior were identified as: (1) recognizing the risk, (2) identifying risk-reduction strategies, (3) weighing consequences, and (4) implementing the least risky option. ◦ Impaired information processing might inhibit the first stage of this process, executive dysfunction and slowed information- processing speed the second and third, and lack of impulse control the last.  Medication Adherence  In the HAART era, one primary cause of HIV treatment failure is resistance to antiretroviral medications, an outcome that both has widespread implications for HIV management and is closely linked with suboptimal medication adherence.  For instance, one early review found that across several studies, non adherence to one medication in a triple combination regimen resulted in, not only an increased viral load, but also viral resistance to all three medications.  A number of studies have found associations between cognitive factors such as memory impairment and executive dysfunction and medication adherence.  A study of adherence found that both neurocognitive impairment and the complexity of a medication regimen were predictive of lower adherence rates; cognitively impaired participants prescribed more complex regimens demonstrated the lowest rates of adherence.  The cognitive impairments most closely associated with poor adherence were deficits in executive function, memory, and attention. A study spurred by the increasing existence of an older HIV-infected patient population, confirmed the impact of cognitive impairment among older adults, a group with better overall medication adherence. The authors acknowledged the possibility of a bidirectional influence, wherein poor adherence may contribute to cognitive dysfunction just as readily as impaired executive function may impede adherence.  Further, it was found that in some instances, although the non-adherent individuals remembered to perform the prescribed task, they did so at the wrong time.  Researchers have suggested that non-adherent individuals have cognitive deficits that hinder their ability to adequately monitor time, thereby missing cues to take scheduled medication doses.  In a study measuring literacy in conjunction with cognitive function among HIV-infected injection drug users, the lowest adherence rates were found in the group with both low literacy and cognitive impairment. HIV Risk-Reduction Interventions  The impaired new learning, information processing, and memory seen in HIV-infected individuals, substance abusers, and the mentally ill may prevent appropriate acquisition and retention of behavioral content conveyed in traditional risk-reduction programs.  Moreover, cognitive impairment has been found to affect other behavioral predictors of intervention effectiveness, such as motivation.  A more recent review suggested that cognitive rehabilitation strategies should be incorporated into treatment, particularly in cases of executive dysfunction. Pharmacological Interventions A number of pharmacological alternatives have been found to assist the recovery of cognitive function or to mitigate impairment in the risk groups discussed. Opioid Substitution Therapy Treatment for drug dependence for HIV-infected individuals not only increases access to care but also facilitates adherence and reduces injection-related risk behaviors. Treatment of Mental Illness  By treating psychiatric symptoms and stabilizing mood, the primary effect of medication may be to limit the HIV risk behaviors and non- adherence to HAART associated with mental illness.  In HIV-infected individuals with HAND, low-dose lithium was found to improve global neuropsychological function, suggesting it may mitigate HIV- related cognitive impairment. Highly Active Antiretroviral Therapy  Findings regarding the impact of HAART on cognitive function have been particularly promising.  Studies have found that HAART reduces viral levels in the plasma and cerebrospinal fluid of infected individuals and improves neurocognitive function.  It has also resulted in a decrease in depressive symptoms that has been demonstrated to affect neurocognitive function. Behavioral Interventions Successful behavioral risk- reduction interventions must tailor learning to those likely to be at least minimally cognitively impaired, either by incorporating strategies to remediate impairment or by incorporating motivation and reinforcing behavioral skills. Cognitive Remediation  Several therapeutic approaches have been identified as effective at remediating the effects of cognitive impairment on risk behaviors and adherence.  For schizophrenics, cognitive adaptation training, which employs environmental supports such as checklists, alarms, and organization to cue adaptive behaviors and adherence, increased adherence to oral antipsychotic medications as measured during the 6 months after training.  Among former drug users, the extent of cognitive recovery was found to increase through cognitive remediation focusing on memory training and the development of problem-solving strategies.  Behaviour models  The harm-reduction intervention was informed by the Information-Motivation-Behavior (IMB) model of HIV-risk reduction, which holds that effective interventions should include information relevant to HIV transmission, motivation to practice risk-reduction behavior, and behavioral skills, including specific behaviors such as needle cleaning and condom application.  Interventions based on the IMB model have been found to be effective in reducing HIV risk behaviors among cognitive impairment risk groups.  In a study of adults receiving outpatient psychiatric care, patients receiving HIV-risk-reduction interventions based on the IMB model had significantly improved sexual risk behaviors compared to those receiving standard care, including stronger condom use intentions, fewer new sexually transmitted infections, fewer casual sex partners, and less unprotected sex. Integration Evidence suggests that interventions informed by cognitive limitations are more effective for at-risk groups. Such interventions are only feasible, however, if they can be incorporated into other treatment programs. Conclusions and Future Directions Understanding the close, bidirectional relationship between cognitive impairment and HIV risk factors is crucial to effectively reducing HIV risk. Ultimately, better understanding and addressing cognitive impairment could significantly enhance HIV prevention and care. Kathy Lawler and others (2010): ◦ 38% met criteria for neurocognitive impairment  Also showed lower scores on verbal learning test  Slower processing speed  Were older  Low education level  24% were diagnosed with depression but depression not linked to neurocognitive impairement