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David E. Vance, PhD, MGS
Associate Professor, School of Nursing, University of Alabama at Birmingham, Birmingham, AL
Shameka C. Humphrey, MSN, RN
PhD Student, School of Nursing, University of Alabama at Birmingham, Birmingham, AL
Gwendolyn D. Jones, PhD
Assistant Professor, Tuskegee University, Tuskegee, AL
Thanks to the effectiveness of combination Antiretroviral Therapy (cART), people are aging with HIV, and in many cases doing so successfully. Although we still struggle without a cure, this remains an exciting period in combating this epidemic in that prognosis and life spans are greatly improved. Yet, challenges remain as we observe either accelerated or accentuated aging in many with this disease in several areas (i.e., cardiovascular, renal, and metabolic disease; systemic inflammation); however, one area has received particular attention – brain health, specifically cognition.
In addition to the immune system, HIV also damages the nervous system. Although HIV does not infect neurons; it indirectly damages them through many other processes. HIV crosses the blood brain barrier, infects glial cells which normally support neuronal function, and creates a cascade of proinflammatory and neurotoxic molecules that disrupt brain homeostasis which damages or destroys neurons. For this reason, preventing HIV from replicating and crossing the blood brain barrier is one of the major strategies for protecting the nervous system. Yet, despite cART reducing plasma viral load (i.e., the amount of HIV viral RNA floating in the blood), the medications used to treat HIV are not equally effective in crossing the blood brain barrier and preventing HIV from replicating in the brain. In fact, the brain is one of the reservoirs in the body where HIV can elude cART. Even though some cART medications are more effective than others in crossing the blood brain barrier and preventing replication in the brain, the immune system response to HIV creates systemic inflammation that can also be damaging to the brain. Coupled with co-morbidities (i.e., hepatitis C), metabolic co-morbidities associated with cART, past/current substance use, and mental health problems often observed in many adults with HIV, these factors further contribute to poorer brain health (Vance 2014).
Poorer brain health is expressed in varying degrees of cognitive functioning. In a sample of 1555 adults with HIV from across six US sites, Heaton and colleagues (Heaton 2010) administered a comprehensive battery and found that 52% experienced observable cognitive impairment (i.e., 33% with asymptomatic neurocognitive impairment, 5% with confounded neurocognitive impairment, 12% with mild neurocognitive disorder, and 2% with HIV-associated dementia). However, the concern with health professionals is that in such a cognitively vulnerable population that is aging, age-related cognitive declines may emerge sooner and be more severe.
In one of our studies sponsored by the National Institute of Mental Health (Vance 2013), we administered a neuropsychology battery to 162 younger (<50) and older (>50) adults with and without HIV. In general, we found that older adults performed the worst on measures of speed of processing, memory, and executive functioning; then, older adults without HIV and younger adults with HIV performed at comparable levels; and finally, younger adults with HIV performed the best. This and other studies have found similar findings. Despite such group trends, individual differences in these groups were observed with some older adults with HIV performing well cognitively for their age. Also, it is important to keep in mind that as mentioned in the Heaton and colleagues (Heaton 2010) study above, 48% exhibited normal, or better, cognitive functioning. Why some individuals with HIV are protected more from such cognitive impairments than others can be conceptualized through the concepts of cognitive reserve, positive neuroplasticity, and negative neuroplasticity.
Cognitive reserve refers to the brain’s ability to absorb physiological insults (i.e., inflammation, concussion, diabetes) and yet remain functional in allowing cognition to emerge. Such cognitive reserve consists of the strength, density, number, and quality of the connections between neurons that support cognition. With numerous connections, when one path is disrupted due to an insult, neural communication can be rerouted along adjacent neural pathways which allow cognition to continue. This is best observed in the enriched environmental experimental paradigm.
In this paradigm, genetically similar rats are randomly assigned to one of three conditions: Enriched, standard, or impoverished (Vance 2012a). In the enriched environment, several rats are placed in a large cage with toys that are exchanged with new toys periodically, so they can socially interact and play with novel objects. In the standard environment, rats are placed three to a cage with no toys, but at least they can socially interact. In the impoverished environment, rats are placed in isolation with no toys, so they do not socially interact. Researchers have observed that rats placed in the enriched environment perform better on maze performance tasks, a proxy of cognitive functioning, and have heavier brains and more sophisticated connections between neurons than rats placed in the standard and impoverished environments. Likewise, rats in the standard environment display a similar pattern of maze performance and brain morphology compared to those in the impoverished environment. The process by which rats in the enriched environment had better cognitive reserve is referred to as positive neuroplasticity. Meanwhile, the process by which rats in the impoverished environment had poorer cognitive reserve is referred to as negative neuroplasticity. Although beyond the scope of this brief article, human studies also have demonstrated these processes of cognitive reserve and neuroplasticity. For example, Boyke and colleagues (Boyke 2008) observed growth and decline in brain structures (i.e., hippocampus, nucleus accumbens) in older adults as they were taught how to juggle in a 3-ball cascade pattern and then stopped practicing how to juggle, respectively. Likewise, studies demonstrate that older adults with social contact and more educational attainment may have more cognitive reserve which delays the onset of dementia.
When we consider the social, physical, and physiological environment of adults with HIV, especially as they age, it is clear that there are multiple factors associated with facilitating positive and negative neuroplasticity. Factors associated with positive neuroplasticity are education, physical exercise, mental exercise, proper nutrition, proper sleep, and cognitive remediation therapy. Factors associated with negative neuroplasticity are non-stimulating activities, poor emotional health, sedentary lifestyle, substance use, and social isolation (Vance 2009). These factors are particularly relevant given that studies show that many adults with HIV experience low educational attainment, socially withdraw due to stigma, have a current/past history of substance abuse, and suffer from a variety of mood disorders such as depression and PTSD (Vance 2014). Fortunately, we do know that positive neuroplasticity works in adults with HIV. In our pre-post two-group experimental study, we randomized 46 middle-aged (40+) and older adults with HIV into either a cognitive remediation group, called speed of processing training, or a no-contact control group (Vance 2012). Those in the speed of processing training group received 8-10 hours of computerized training over approximately a 5-week period. Around 6 weeks after baseline, we observed that those who received this speed of processing training, reflective of positive neuroplasticity, improved on a measure of visual speed of processing (i.e., Useful Field of View Test) and a laboratory-based measure of everyday functioning (i.e., Timed Instrumental Activities of Daily Living Test) compared to the no-contact control group. Clearly, adults aging with HIV can benefit from activities and health behaviors that can promote positive neuroplasticity which obviously supports cognitive reserve and cognition which facilitates everyday functioning.
Given these factors of positive and negative neuroplasticity, it is conceivable for adults aging with HIV to benefit from a tailored behavioral program designed to support cognitive reserve and positive neuroplasticity, which would thereby improve cognitive functioning. We proposed a cognitive prescription protocol in which a therapist can guide patients to develop individualized behavioral goals to improve brain health and cognition (Vance 2011). For example, one patient may make behavioral goals in the area of mood (i.e., daily take antidepressants as prescribed), physical activity (i.e., go for a 1 mile walk 3x a week), and nutrition (i.e., eat salmon 2x a week because it is rich in omega-3 fatty acids), all of which support brain health. Although such a structured behavioral program may be helpful, many individuals may not need such explicit guidance. Regardless of whether one does or does not have HIV, the general tenet is that which is good for the body also supports positive neuroplasticity and undermines negative neuroplasticity which is essential for brain health. Although HIV has detrimental effects on the brain, there are health behaviors and mental stimulating activities that adults aging with HIV can implement to promote successful cognitive aging. For more detailed guidelines of such efforts to prevent and treat cognitive problems in HIV, please see Vance, Fazeli, Moneyham, Keltner, and Raper (Vance 2013a).