Researchers in the U.S. have found that some ART users can sometimes develop problems with memory and thinking clearly. In cases where these problems persist and are of at least moderate intensity, researchers have found that activities of daily living can be affected, such as the following:
- financial management
- remembering medical appointments
- adherence -- taking anti-HIV medicines every day exactly as directed
Another issue that HIV-positive people and their care providers have to consider is the impact of aging on neurocognitive abilities. In this report we present some ideas from researchers who have reviewed the issues and studies about aging and HIV and the impact of both of these factors on brain health.
Is it AIDS or Age?
In one study of 161 people, researchers grouped people by different categories (over 50 years or under 50 years of age) and by HIV status (positive and negative). They found that as a group, older HIV-positive people had poorer assessments of neurocognitive function than younger HIV-positive people. Among HIV-negative people, a similar trend was found; that is, older people had poorer neurocognitive testing results than younger people.
A major drawback of this study is that it was cross-sectional in design. This is similar to a snapshot of people -- it only gives information from one point in time and does not provide information about changes that happen over time. Such changes over time can be obtained from a study of a different design -- a longitudinal study. However, such studies are expensive and can be cumbersome. Still it seems reasonable to conclude, based on the cross-sectional study, that age has an impact on the neurocognitive abilities of HIV-positive people. Bear in mind that the impact of age on the brain will vary considerably from one person to another.
Some U.S. researchers who study aging and the brain suggest that one factor that plays a role in the decline of the aging brain in some ART users is "cognitive reserve," which they define as "the amount of damage that the brain can absorb and yet remain functioning"
They further suggest that "cognitive reserve may explain why individuals experience [different] rates of change in cognitive function such that cognitive reserve capacity may provide a buffer against cognitive decline."
Lessons From Mice
The U.S. researchers underscore findings from experiments with mice that may serve as a broad guide for research on helping to improve brain health and cognitive reserve.
In summary, researchers have found that placing mice in an enriched environment with stimulating toys and social contact with other mice helps their brains to thrive. Specifically, researchers have found that the brains of these mice produced chemical signals that encourage brain cells to make and strengthen their connections to other brain cells. Furthermore, mice placed in an enriched environment are better at navigating mazes than mice that are placed in a less stimulating standard laboratory environment.
Learning From Drivers
In a study published in 2005, neuroscientists in London, UK, studied 35 healthy participants, 18 of whom drove taxis and 17 others who drove buses. These participants underwent extensive neuropsychological testing and had MRI (magnetic resonance imaging) scans of their brain taken and analysed.
The researchers noted that taxi drivers had to undergo between two and four years of training in order to effectively navigate London and learn about points of interest. In contrast, bus drivers only received about six weeks of training and drove fixed routes. Taxi drivers generally do not drive fixed routes.
Other neuroscientists have proposed that the taxi driver training program and work is somewhat analogous to the enriched environment previously described in the mouse experiments. Also, the bus driving would stand in for the standard environment in the previous experiments with mice.
The UK researchers found that parts of the brains of taxi drivers were larger than those of bus drivers in their study.
Commenting on these experiments with mice and people, as well as other studies, neuroscientists have suggested that learning new information helps to stimulate and develop the brain, even in adults.
Some Factors That Can Decrease Cognitive Reserve
Researchers have noted that the following factors likely play a role in reducing a person's cognitive reserve:
- anxiety, depression and other mood issues
- addiction and substance use
- shrinking social interaction -- HIV infection carries stigma, which can cause some people to experience social isolation. At least one study has found that some older HIV-positive people have fragile social networks.
- co-morbidities -- emerging research suggests that some of the issues associated with aging, such as elevated blood pressure, pre-diabetes and diabetes, abnormal cholesterol levels, kidney disease, cardiovascular disease and so on, can all indirectly or directly reduce cognitive reserve.
- Infections -- emerging research suggests that hepatitis C virus co-infection and syphilis can also affect the brain's cognitive abilities.
A Closer Look at Emotional and Mental Health
Anxiety and depression are relatively common among people with HIV. Ideally, doctors would screen their patients for these conditions and refer or discuss treatment options. If left untreated, emotional and mental health problems can reduce a person's quality of life and overall health. Researchers have noted that people who experience depression and anxiety can inadvertently focus on past mistakes and other unhelpful negative thoughts. Neuroscientists have found that constantly reviewing and reliving unhelpful thoughts and experiences can "prevent other thoughts from emerging." This process reduces a person's ability to resolve complex emotional issues. In studies with HIV-negative people, researchers have found that treating emotional and mental health issues "may help reverse or prevent" some neurocognitive problems. There is no reason the same beneficial effect of therapy should not occur in HIV-positive people experiencing emotional and mental distress. Untreated emotional and mental health issues likely contribute to increased inflammation within the brain and perhaps the entire body.
The Benefit of HIV Therapy
Shortly after HIV spreads from the point of first contact (usually the wet tissues of the anus, penis and vagina) it reaches the body's organs, including the brain. Therefore, starting ART as soon after diagnosis as possible is important not only for restricting the spread of the virus, but also for reducing the amount of HIV and HIV-infected cells in the body's tissues and organs. HIV-infected cells release chemical signals and proteins that can cause brain cells to become dysfunctional.
Some HIV-negative people can have hurtful and unpleasant attitudes toward people who are HIV positive. Repeated exposure to such behaviour can be stressful and can cause some HIV-positive people to disengage from the wider community and become socially isolated. This last point is important because meaningful social interaction is good for the brain.
It is important to strengthen and extend social networks as people age. Joining clubs, teams, book groups, gyms and other activities where social interaction takes place are ways that can incite the process for making new friends.
Higher-Than-Normal Blood Pressure (Hypertension)
Researchers have found that hypertension can affect cognition in HIV-negative people. Also, reducing hypertension has been found to improve cognition.
Brain cells need regular and relatively stable levels of the sugar glucose. These cells convert glucose into energy and use it to power their activities. Researchers have found that elevated levels of blood sugar and the hormone insulin are linked to decreased cognitive functioning in some HIV-positive people. Treating these issues with changes to the diet, exercise and medicines can help normalize blood sugar levels and improve cognitive function.
Exercises for the Mind
All of the following interventions generally improve mood and, in some cases, make life more interesting and stimulate the brain:
- techniques to reduce the impact of stress -- physical exercise, meditation, Tai Chi, yoga
- brain fitness exercises (we detail these later in this issue of TreatmentUpdate)
- learning a new language or skill
- playing games
- reading books
- taking a college course
Areas for Future Research
Emerging research suggests that there are many possible ideas that could be studied in clinical trials with HIV-positive people for their potential on delaying the decline of the brain, such as the following:
- a Mediterranean diet
- supplements of probiotics
- regular intensive exercise
- certain antidepressants -- The antidepressant lithium stimulates the brain to produce chemical signals that can improve brain health and may help to reduce HIV-related brain injury. However, people who use lithium require frequent monitoring to ensure that they do not develop side effects. Other antidepressants might also be worth studying for the same purpose.
- music designed to change brain waves to a state similar to that detected in people who are meditating. This type of music is called binaural beat therapy.
In this issue of TreatmentUpdate, we discuss other ideas that researchers are investigating to help the brains of HIV-positive people.
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