An Introduction to Neurocognitive Deficits in HIV

People living with HIV worry about their memory, and with good reason. As their life expectancy increases, it is becoming clear that this chronic illness affects both cognition and mental health, even with excellent systemic viral control. Although we are only beginning to understand these emerging co- morbidities, they are likely the result of multiple interacting processes. HIV has direct effects on the brain: highly active anti-retroviral therapy (HAART) may not fully penetrate the CNS, providing a reservoir for viral replication, and inflammation may affect brain function. Anti-retrovirals may themselves be neurotoxic, as may common co-morbidities such as aging, depression, cerebrovascular disease, substance abuse and hepatitis C infection. The experience of living with chronic infection can threaten brain health by affecting stress levels, coping, physical health, and social supports.

Although the burden of poor brain health in HIV in Canada is unknown, it is likely to be high. Recent studies in other developed countries, using comprehensive neuropsychological assessment, report a prevalence of (primarily mild) cognitive impairment of 30-50%. Even higher rates have been documented in those over the age of 50, a rapidly expanding group at the frontier of existing knowledge about the combined effects of aging and longstanding HIV infection. Depression is also common in HIV infection, with population-based prevalence of major depressive disorder estimated as high as 36%. Mood disorders can affect cognition even in otherwise healthy individuals. In HIV specifically, cognitive complaints have been associated with depressive symptoms more consistently than with objective cognitive performance. It may be that depressive symptoms and cognitive difficulties are two facets of brain dysfunction, or that depression affects cognitive performance (in life and in testing situations) through effects on attention or motivation. Impaired cognition and depression, whether together or separately, strike patients in their productive years, and can affect medication adherence, occupational and social function, quality of life, and even accelerate mortality. Progress in understanding the heterogeneous, multi-factorial nature of compromised brain health in HIV will require careful clinical characterization, including of its evolution over time, accompanied by hypothesis-driven research focused on specific clinical phenotypes. Progress in predicting, treating and mitigating the impact of poor brain health will require better,

The nomenclature describing cognitive impairment, and the modalities used to measure cognition vary across clinical disciplines, hindering interdisciplinary research. For this proposal, we have chosen to use the term cognitive deficit and its positive opposite, cognitive ability; we also distinguish between directly measured cognitive deficits (ie neuropsychological tests) and perceived cognitive deficits reported as symptoms (here measured using validated questionnaires). This method is broadly consistent with the requirements of the current diagnostic criteria for HIV-Associated Neurocognitive Disorders (HAND). Our view of cognition departs from current diagnostic approaches by focusing on cognitive ability as a “quantity”. We propose that declines in cognitive ability compared to the individual’s own baseline will be the most useful trigger for intervention, and that stability or improvements are likely to be more important to the patient than whether they meet arbitrary diagnostic thresholds. Rigid use of diagnostic categories may prevent recognition of real difficulties, and limit access to useful interventions for patients with high (but deteriorating) cognitive abilities. Current approaches to diagnosis rely on neuropsychological testing. This is resource-intensive and not universally available in the Canadian context. and limit access to useful interventions for patients with high (but deteriorating) cognitive abilities. Current approaches to diagnosis rely on neuropsychological testing. This is resource-intensive and not universally available in the Canadian context. and limit access to useful interventions for patients with high (but deteriorating) cognitive abilities. Current approaches to diagnosis rely on neuropsychological testing. This is resource-intensive and not universally available in the Canadian context.

Front-line health care providers who must judge whom and when to refer are poorly equipped to respond to patients’ concerns about cognition: What symptoms signal difficulties that warrant further investigation or intervention? What interventions are appropriate? Are there patients who do not report symptoms who nonetheless have deficits and would benefit from assessment and treatment? How should they be identified? We recognize that a key challenge in this area is to understand the link between what patients are saying, which is what matters to them, and what the objective tests indicate. Developing better ways to measure both symptoms and signs that are feasible in everyday practice, and tuned to the full range of abilities in the population is a crucial first step. While better measurement and thorough description of the clinical phenomenology and its evolution are necessary, they are not sufficient. We need to link this level of study to work on the underlying pathogenic mechanisms if we are to develop rational approaches to treatment.

People with HIV cannot afford to wait for researchers to fully understand this complexity. They are facing brain health challenges today, with real meaning for their everyday function. Research in other chronic neurological disorders has provided the tools to help these people now. In particular, research on the effects of exercise, self-management and cognitive training in healthy aging and mild cognitive impairment (MCI) shows promise in improving cognitive functions that are also commonly affected in HIV. There is more than a conceptual parallel between these conditions. Subtle pathological aging changes are found in the brains of people with HIV. We hypothesize that interventions proved useful in aging and MCI will make a difference in mood, cognitive performance,