Neurocognitive impairment in people living with HIV

With the introduction of highly active antiretroviral therapy (or HAART), there has been a dramatic reduction in HIV-related central nervous system (CNS) opportunistic infections and severe cognitive disorders in people living with HIV (PLWH). People who have access to medications and quality care can enjoy a full and productive life. Although there has been an increase in the accessibility of treatment, it is disheartening to see that there are still a significant number of cases of neurocognitive impairment in the HAART era. Concerns about neurocognitive impairment persist for PLWH. 

Neurocognitive impairment (NCI) is a general term to describe dysfunction that involves executive, motor, attention, memory, and less commonly language impairments to varying severity and frequency. The range of HIV-related NCI is called HIV-associated neurocognitive disorders (HAND). HAND syndrome is classified as asymptomatic neurocognitive impairment (ANI), mild neurocognitive impairment (MCI), or HIV-associated dementia (HAD). 

ANI is challenging to diagnose despite using formal neuropsychological testing to evaluate performance in several cognitive domains. Unfortunately, the broad definition of ANI means up to 20% of the cognitively typical population of PLWH is classified as sustaining ANI. There is some evidence to suggest that people with ANI may progress to symptomatic HAND, thus making early accurate diagnosis important. 

MCI, or mild neurocognitive disorder, involves noticeable cognitive impairment in two cognitive domains but does not always disrupt daily activities or functioning. While symptoms of MCI are easier to recognize compared to ANI, it is difficult to ascertain whether they result from HIV or other causes. Some people living with HIV may also manage mental health conditions such as depression, ADHD, or other learning disabilities. Determining the root cause of cognitive impairment requires an extensive evaluation by a mental health professional. 

Thanks to HAART, we see less of the more severe forms of HAND caused by central nervous system damage from uncontrolled HIV replication in cerebrospinal fluid and brain tissue. People with HIV-associated dementia, or HAD, experience moderate to severe impairments in cognitive functions and considerable difficulties in everyday functioning. Antiretroviral medications that penetrate the blood-brain barrier can improve cognitive impairment, especially as people achieve complete viral suppression. Why then do we still have concerns about neurocognitive impairment for PLWH in the age of HAART?

Unfortunately, despite successful viral suppression, virus that escapes into the cerebrospinal fluid might explain some cases where HAND persists. While most antiretroviral medications penetrate the blood-brain barrier, poor drug concentration in the central nervous system may result in milder forms of cognitive impairment. Other explanations include persistent immune activation or chronic inflammation. Shortly after starting treatment, people typically experience a sharp decrease of systemic inflammation but not to normal levels. Other medical conditions such as cerebrovascular disease and hepatitis C co-infection may contribute to neurocognitive impairment.

Aging with HIV is another factor that challenges our complete understanding of HAND. There is an ongoing debate about premature aging or accelerated aging for some age-related medical conditions like cardiovascular disease in PLWH. It is not entirely clear if this suspected pattern of aging is present in neurocognition. Several studies suggest that HIV might accelerate brain aging through chronic neuroinflammation. However, study findings are inconsistent and complicated by comorbidities and the significant differences in life trajectories of PLWH. The pathogenesis of HAND continues to be studied, as are the roles of age, antiretroviral neurotoxicity, and comorbidities. 

Biomarkers and improved assessment tools will help further our understanding of HIV and neurocognition so that we can identify neurocognitive impairment in the asymptomatic stage before further deterioration. Several neuroimaging techniques have been used to evaluate brain structure and function but are not widely used in clinical practice. 

What you can do to keep sharp: 

Stay informed 

You’re doing this now! Learning about HAND and staying informed on all things HIV will serve you well in the long run. Increasing your understanding of common co-occurring conditions can inform your conversations with healthcare providers. If you have concerns about cognitive function, talk to your primary care doctor, who can refer you to a specialist. Stay engaged in treatment and let your doctor know that you wish to be a collaborative partner in your care. Always ask questions and report any new symptoms or concerns you might have about neurocognitive impairment.

Focus on mental health and well-being

Take care of your emotional well-being and mental health. Depression, learning disabilities that persist in adulthood, age-related cognitive decline, and other mental health concerns may contribute to decreased cognitive functioning. For example, people with untreated depression often report difficulty with memory and attention or experiencing “brain fog” as a result of fatigue and depression. It is important to continue treatment with a licensed mental health professional should any of these issues be relevant to you. 

After you read this, I’d like you to set some time aside to do a self-check inventory. This is an opportunity to reflect on your internal process and environment and ask yourself a few key questions. How are you feeling right now? Much of what a person feels is caused by what they say to themselves. People talk to themselves all day long with little awareness of it. Self-talk is automatic and carried out repeatedly. When we are not sure why something is the way it is, we often start looking outside of ourselves for the source of unhappiness. That’s okay to do! But be sure to check your self-talk and internal process. Continue your self-check by reflecting on how you spend most of your days. What takes a lot of time and effort? Are you engaging in activities or hobbies that you enjoy and find fulfilling? How much sleep are you getting on average? Can you quickly name a few reliable and trustworthy friends or family members to reach out to if you were in a bind? Remember to conduct a self-check throughout the year.

Nutrition and exercise 

There is plenty of evidence to suggest that diet and exercise have a positive impact on brain health. Maintaining a healthy diet combined with aerobic and resistance exercise is an effective way to counter age-related cognitive decline, and will help with HAND. Avoid tobacco, alcohol, and other substances that are known to negatively impact brain health. Eat a nutrient-rich diet that consists of fruits and vegetables while minimizing the amount of processed food you eat. 

Make time for exercise. I’ve often heard (and have said to myself), “Well, I’m not a morning person and I’m too tired at the end of the day. I don’t know when I can exercise!” We manage to find time to do things for work or other people but are not so great at making time for ourselves. Don’t put off things that are important to your health and well-being. Schedule time in advance if you must for exercise and make it a habit. Your brain will thank you for it.

Engage in new and novel activities 

Finally, studies have shown that novel activities and experiences shape our brain’s structure and organization. Activities that stimulate the mind like reading and puzzles will help keep you sharp. The Synapse Project conducted a study with 221 participants ranging in age from 60 to 90 to assess the effect of sustained engagement on cognitive function. A key takeaway from the study was activities that require active learning and sustained use of working memory, long-term memory, and other executive processes caused a significant increase in episodic memory. Episodic memory refers to a type of memory involved in recalling specific situations or events. Even the experience of learning something new can reinforce a growth mindset and boost confidence in the ability to learn something new.

Conclusion 

Remember that your brain is just as important as the other organs of your body, and it changes as you grow older. It’s normal for people to become a little more forgetful or to take a bit longer to remember a word or name now and then as they age. However, having consistent or increasing concerns about your cognitive performance warrants further exploration. If you commonly lose your train of thought, have difficulty with tracking a conversation, or struggle to find your way around a familiar environment, talk to your doctor. Mild neurocognitive impairment may not always be preventable. But research shows there are many things you can do to prevent it or slow its progression.