The Synergistic Effects of HIV, Diabetes, and Aging on Cognition: Implications for Practice and Research

In addition to the obvious health problems and/or physical limitations associated with HIV, diabetes, and aging, each of these are known to independently affect cognitive functioning. While this relationship to cognition does not necessarily mean frank cognitive impairments are inevitable with HIV, diabetes, and aging, it does entail that each of these conditions may lead to poorer cognitive performance compared to younger adults and individuals without HIV and diabetes. Many individuals may be aware of the physical symptoms associated with these diseases, but may be unaware of the cognitive outcomes associated with HIV and diabetes, especially if not controlled by medication and a healthy lifestyle. Additionally, individuals may be unaware of the significance of maintaining optimal cognitive functioning in order to maintain optimal everyday functioning abilities such as driving, cooking, managing medication regimens, and negotiating finances. Given that highly active antiretroviral therapy (HAART) has allowed individuals with HIV to live to reach older adulthood, and that dysglycemia and/or type 2 diabetes can be a metabolic side effect of these medications (Biron et al., 2012; Norbiato, 2012; Raper, 2010), it is reasonable to assume that there is a subset of individuals aging with HIV and diabetes, which may become more prevalent as individuals continue to age with HIV in the coming decades. Thus, the purpose of this article is to inform healthcare providers and researchers about the cognitive outcomes associated with HIV, diabetes, and aging independently within the context of cognitive reserve, and then to examine the potential synergistic effects of these conditions in individuals living with all three (Figure 1). This article also incorporates potential intervention strategies to protect and possibly improve cognitive functioning, or at the very least mitigate cognitive loss, in this population. Figure 1 The synergistic effects of HIV, type 2 diabetes, and aging on cognition and cognitive reserve. Cognitive Reserve Cognitive reserve, sometimes referred to as brain reserve, refers to the amount of damage that neurons and neuronal connections can absorb and yet support the physiological function needed to support cognition (Restak, 2009; Stern, 2009; Vance & Wright, 2009). Thus, the more complex and sophisticated the connections between neurons are, the better they are able to communicate and support cognition, even in lieu of disease-related insults. For example, in a simplistic example, the left panel in Figure 2 shows a complex and intricate connection between neurons A – G such that neural communication can be transmitted from A to G from which cognition emerges. In the right panel in Figure 2, the connections between neurons A – G is compromised due to cell death of neurons C, D, and F possibly due to amyloid plaque, neuroinflammation, and oxidative stress, respectively. Yet the remaining connections (i.e., cognitive reserve) allow the neural communication to be transmitted from A to G via paths from A – B – E—G, therefore allowing cognition to emerge despite such damage. Such rerouting of neural communication is similar to other physiological processes. For example, when blood vessels are blocked in occlusive coronary heart disease, the risk of myocardial ischemia is reduced by coronary collateral arteries rerouting blood flow around such blockage (Berry et al., 2007). Figure 2 Cognitive reserve and an example of collateral neural communication. Darkened neurons represent damaged or dead neurons that can no longer transmit neural information. This cognitive reserve is supported or reduced by positive neuroplasticity or negative neuroplasticity, respectively. Positive neuroplasticity refers to those physiological activities in the brain that help form more intricate and sophisticated neural connections. Factors that support positive neuroplasticity are exposure to novel and stimulating stimuli (e.g., education, travel, learning a new language) and conditions that promote good overall health (e.g., physical exercise, good sleep hygiene). Likewise, negative neuroplasticity refers to those physiological activities in the brain that abate or stymie the formation of more intricate and sophisticated neural connections. Factors that support negative neuroplasticity are lack of exposure to novel and stimulating stimuli (e.g., lack of social contact) and conditions that promote poor overall health (e.g., substance abuse, co-morbidities) (Vance & Crowe, 2006; Vance & Wright, 2009). These processes of positive and negative neuroplasticity have been observed in animal and human studies alike (Restak, 2009; Stern, 2009; Vance & Crowe, 2006; Vance & Wright, 2009). For example, in a seminal study involving 60 community-dwelling older adults (Mage = 60), Boyke and colleagues (2008) conducted brain MRIs to these participants (i.e., Time 1). Then over a 3-month period, these researchers instructed these participants on how to juggle for at least 1 minute in a 3-ball cascade pattern. At which point, brain MRIs of these 25 participants who were able to learn this task were conducted. Finally, after these 25 participants stopped juggling, brain MRIs were conducted again approximately 3 months later (i.e., Time 3). These researchers found that from Time 1 to Time 2 when the participants were challenged with the stimulating activity of learning to juggle, the size of their hippocampi and nucleus accumbens – brain structures important for memory – increased; this change in brain physiology reflects positive neuroplasticity. Also, these researchers found that from Time 2 to Time 3 as participants were no longer challenged with practicing juggling, the size of their hippocampi and nucleus accumbens decreased; this change in brain physiology reflects negative neuroplasticity. From this and several other studies (Brayne et al., 2010; Roe et al., 2008), activities that support cognitive reserve have been shown to delay cognitive impairment or the on-set of dementia, even when the brain experiences neurological insults such as observed with transient ischemic attacks, hypertension, heart disease, and Alzheimer’s disease. It is within this context of cognitive reserve that the cognitive impairments associated with HIV, type 2 diabetes, aging, and the combination thereof are discussed.