The Synergistic Effects of HIV, Diabetes, and Aging on Cognition

Abstract

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.

Aging and Neurocognitive Functioning in HIV-Infected Women: a Review of the Literature Involving the Women’s Interagency HIV Study

“…58 In addition, studies in uninfected adults show that with advancing age, women perceive more stress than men. 59 Such stress may lead to metabolic disorders such as insulin resistance and diabetes.…”

Trends and predictors of non‐communicable disease multimorbidity among adults living with HIV and receiving antiretroviral therapy in Brazil

“…PLHIV are living longer and accumulating NCDs, resulting in multimorbidity, defined as two or more chronic NCDs . In PLHIV , NCDs have been associated with decreased quality of life and physical function, dementia and mortality .…”

Redefining Aging in HIV Infection Using Phenotypes

“…More specifically, a greater medical comorbidity burden (mostly for diabetes and malignancy), assessed by the Charlson Comorbidity Index [ 79 ], in older HIV-infected adults was associated with global NCI and related functional declines and lower physical health-related quality of life [ 12 ]. Other data in older HIV-infected adults are supportive of this finding—reporting that these individuals develop metabolic dysfunction (and other comorbidities) disorders leading to type 2 diabetes and NCI, through depleting cognitive reserve, that can impair everyday functioning and reduce quality of life [ 80 ]. In line with these findings, changes in VACS Index scores, which is a composite marker of HIV disease severity, including age, HIV-related factors (current plasma HIV RNA load and CD4 cell counts) and “non-HIV-associated biomarkers” (indicators of renal and hepatic function, anemia, and HCV co-infection), correspond to longitudinal changes in neurocognitive function among middle/aged HIV-infected individuals [ 81 ].…”

“…Other possibilities for the adverse impact of HIV-associated mental health comorbidities on cognition include (1) competing for cognitive resources through rumination (i.e., depressive or suicidal thoughts that prevent other thoughts from emerging), (2) displaying different cognitive profiles (e.g., executive dysfunction is common in schizophrenia), and (3) a convergence of compromising vascular effects (diabetes mellitus, hypertension, and HIV infection). Related to these possibilities, models have been proposed for the synergistic effects of HIV, type 2 diabetes, and aging on cognition [ 80 ]. To further elucidate the role of each of these mechanisms would require separating out components and domains of the cognitive phenotype.…”