Mild brain injuries in HIV often go unrecognized – more needs to be done
Sean B. Rourke, Ph.D., FCAHS
Scientist, Li Ka Shing Knowledge Institute of St. Michael’s
Professor of Psychiatry, University of Toronto
Scientific and Executive Director, Ontario HIV Treatment Network
Director, CIHR Centre for REACH in HIV/AIDS
Director, CIHR Collaborative Centre for Community-Based Research in HIV/AIDS
Director, Universities Without Walls (CIHR STIHR)
Alex Terpstra, MSc (Candidate)
Rehabilitation Sciences Institute, University of Toronto
Coordinator, Health Policy and KTE, Ontario HIV Treatment Network
Community Liaison, The Canadian HIV Cure Enterprise, Institut de Recherches Cliniques de Montréal
Francisco Ibáñez-Carrasco, PhD
Director, Education & Training, Ontario HIV Treatment Network
Manager, Universities Without Walls (CIHR STIHR)
In recent years, the topic of traumatic brain injury has received more and more media attention. We watch with amazement as our favourite Canadian athletes, like Sydney Crosby, perform on the rink, and cringe when they sustain what could be career-ending blows to the head. We’ve learned that these “bell ringers” — which used to be a rite of passage for “real athletes” — are bad for a person’s health. In fact, brain injuries can increase a person’s chance of developing cognitive changes in later life. In some cases, they can even lead to earlier onset of dementia.
Although it’s less well known, and often not well identified, HIV can affect the brain and produce similar changes in cognitive abilities (e.g. attention, memory, and thinking) as concussions. Although 90-95% of people who experience mild concussions and brain injuries recover from these injuries in weeks to months, people who experience mild brain injuries caused by HIV often do not recover. The changes in their brains often persist, fluctuate over time, and never completely reverse.
The brain injuries caused by HIV are extremely challenging for the people affected and for the clinicians caring for them. For people with HIV, the first cognitive changes may be subtle and have no noticeable impact on their day-to-day life. However, over time, the changes can progress and begin to interfere with their ability to carry out daily tasks and activities, like reading, managing medications, and paying attention to conversations in social situations. They can also affect the ability to do more demanding, “multi-tasking” things at work and often result in people getting frustrated, losing confidence, and going on disability. For the doctors caring for people with HIV, subtle cognitive changes are extremely difficult to diagnose and to treat or manage.
Our Centre for Brain Health in HIV at St. Michael’s Hospital in Toronto is one of over a dozen international centres around the world working to identify better ways to assess, screen, treat, and manage HIV-associated cognitive impairments. We are developing clinical treatment guidelines and benchmarks for brain health in HIV/AIDS that will help clinicians manage and support their patients. We are also exploring and testing out different non-pharmacological interventions, such as brain fitness, physical exercise, and mindfulness-based cognitive behaviour therapy, to see if we can identify tools that people with HIV can use to lessen, manage, or even reverse the cognitive changes associated with HIV, and compensate for the impacts they have in their lives.
Although people with HIV are now living longer, they are developing medical complications earlier than people who don’t have HIV. For example, they often develop signs of cardiovascular disease 10-15 years earlier. In our centre, we are also trying to understand how these medical conditions — which often occur in conjunction with other mental health issues, such as depression — may accelerate and increase the cognitive impairments associated with HIV, especially as people age.
How does HIV affect the brain? What is HIV-associated neurocognitive disorder (HAND) and how common is it?
HIV can cause damage to the brain, both directly and indirectly, through inflammation and the release of harmful chemicals. The damaging effects of HIV on the brain can also be magnified by excessive drinking and drug use, as well as by other medical comorbidities, like cardiovascular and liver disease.
Cognitive impairment caused by HIV is called HIV-Associated Neurocognitive Disorder or HAND. Not everyone living with HIV will develop HAND. Among those who do, the level of impairment ranges widely, from nearly undetectable to mild to more severe. The most severe of these conditions is far less common today than it was in the past, thanks to combination antiretroviral therapy (cART) which, in addition to protecting and strengthening the immune system, protects the brain from HIV-related damage. The use of cART has dramatically reduced the prevalence of the most severe forms of HAND. However, despite the protective effects of cART, several research studies, including our own in Toronto, estimate that about 30-55% of middle-aged adults living with HIV still experience some form of HAND.
So, what is HAND?
There are three main conditions/disorders that can occur: (1) asymptomatic neurocognitive impairment or ANI; (2) mild neurocognitive disorder or MND; and (3) HIV-associated dementia or HAD. The earliest stage of HAND, ANI (which occurs in about 1 of 3 people living with HIV), can only be detected using psychometric tests of attention, speed of processing, learning and memory, and thinking skills. These tests are sensitive enough to pick up subtle changes in cognitive abilities that are not apparent in daily life. While people with ANI will have mild and “spotty” cognitive impairments, they are often asymptomatic or symptom-free. The subtle and mild cognitive impairments do not interfere with their day-to-day life. The second milder HAND condition is MND, which affects about 15-20% of persons with HIV. People with MND experience cognitive changes that have a mild, but noticeable impact on their daily activities, including work, school, or social interactions. HAD is the most severe and, now, the rarest form of HAND (<2-3% of persons living with HIV). Most people who develop ANI or MND will not progress to HAD if their HIV is well managed with cART.
Advancing the field and supporting people living with HIV manage HAND — What are we doing at St. Michael’s Hospital?
If there are most often only mild cognitive impairments in HIV and we know in which areas they occur, why can’t we just ask patients what their problems are, diagnose HAND, and develop a treatment plan? Diagnosing HAND is more complicated than this for three reasons. First, what patients tell you about their attention, memory, and thinking skills is highly influenced by how someone is feeling emotionally and physically. For example, when people are feeling down or depressed, or even fatigued, they report cognitive issues that are often temporary and may not signal any “fixed” brain changes at all. Second, the cognitive impairments that people experience are often “spotty” — that is, not everyone will have the same complaints or present them in the same way. Third, many problems that patients report occur commonly as we all age. For example, when we are 60, we do not process or learn information as quickly as we did when we were 20 years old.
In recent years, we have published a significant amount of work that helps to clarify the “signs and symptoms” of HAND, the relationships between “subjective” and “objective” findings, and the factors like physical and mental health (depression) that can interact with and complicate the clinical diagnosis of HAND, particularly the milder forms of HAND. This new knowledge has been very helpful in educating clinicians about the factors in diagnosing and managing HAND. One of the most important clinical issues has been to clarify whether a patient has HAND, signs of major depression, or both — since there are different strategies and interventions to address these conditions. We have also been involved in a recent international initiative with leaders in neurology, neuropsychology, psychiatry, primary care, and infectious disease called Mind Exchange. We have developed clinical assessment, diagnostic, and treatment guidelines for HAND that are now available in open access for practitioners.
Given that there are few neuropsychological services available to clinicians (we are one of only a few HAND clinics in Canada), we have spent considerable time evaluating cognitive screening instruments that clinicians may be able to use to screen clients for HAND in the clinic. According to a recent systematic review we conducted, most of the existing screening tools are relatively good for detecting the more severe forms of HAND, but they performed poorly in diagnosing milder forms of HAND. In fact, most of the studies done had significant methodological weaknesses, including small samples, poor attention to HAND diagnostic issues, and lack of a proper “gold standard” to compare each screening test against. These findings led us to apply to CIHR to conduct a study now underway to address these weaknesses and provide better guidance on the value and utility of a handful of HAND screening tests that could be used with more confidence in the clinic. We have now enrolled about 150 patients and our results are encouraging. We will soon be testing some new screening tools in development in the US, using validated smartphone iPad applications, that may offer even more flexible ability to assess patients in different environments and contexts.
Living well with HAND and managing a mild brain injury Shifting the conversation and dialogue to support and health promotion
In most cases, HAND is a mild, manageable brain injury that people living with HIV can learn to respond and adapt to — much like those growing up with a learning disability or those with persistent effects from a mild traumatic brain injury. In addition to managing the virus through cART, one of the most effective interventions for patients with mild HAND is education and support in adjusting to living with a mild brain injury and disability. Having a mild, persistent brain injury can really shake a person’s sense of self and confidence. People often need a lot of support to learn how to adapt to this new condition that has often developed in subtle ways and gone unnoticed by health care practitioners.
Health promotion strategies are now getting a lot of attention as ways to stop any further cognitive losses and to address any concurrent medical and mental health comorbidities. One of the most effective health promotion interventions starts with a simple statement like: “whatever is good for your heart is often good for your brain.” Activities designed to maintain a healthy heart — such as exercising, eating a healthy diet, getting enough sleep — and addressing harmful habits, such as substance use and smoking — can improve brain health and cognitive abilities. Managing stress, anxiety, and depression can also have a very positive impact on the brain. Treatment for emotional and mental health problems, as well as engaging stress-reducing activities like yoga or meditation, can go a long way in promoting a healthy brain (and heart). Stress-reduction activities are often referred to as “complementary” or “alternative” medicine and recent research has shown they can have a positive overall impact on the lives of people with HIV. In addition to these successful individual approaches, educating and supporting family members or others involved with people who have some form of HAND can help enhance their health.
There is also evidence that some specific activities stimulate the brain and can improve brain health, including: meaningful social interaction and social support, such as outings and activities with friends and family, reading, learning a new language or skill, enrolling in a university course or cooking class, and playing traditional brain games like Sudoku or completing crossword puzzles. A number of private companies are now developing computer and smartphone-based brain games for those interested in sharpening their cognitive skills. We are currently testing out these brain games in pilot studies in our centre and the results so far are encouraging. Most people who do these interventions report significantly fewer cognitive symptoms, which can have a dramatic improvement in their quality of life. Some also show measurable improvements on our tests. We are now preparing for a larger randomized, control trial that we hope will provide more evidence of the impact of these interventions on improving HAND in people living with HIV.
In addition to the success of individually-tailored approaches, health promotion strategies may be improved and enhanced by educating and supporting direct care dyads or family members involved in the daily lives of people with HIV who have some form of HAND.
In all our work, we are building evidence to improve the diagnosis and management of HAND. While more research is needed, we are definitely on the right path.