HIV and the brain

Summary

It has long been known that HIV can negatively affect the brain and lead to cognitive problems, such as HIV-related dementia and milder problems, such as trouble focusing and remembering things. Since the introduction of more effective anti-HIV drugs (highly active antiretroviral therapy or HAART), there has been a dramatic drop in the rate of HIV-associated dementia—the most serious form of cognitive impairment. At the same time, because people living with HIV are living much longer, milder forms of neurocognitive problems are now more prevalent among people living with HIV. Fortunately, there are many things you can do to minimize or reverse the effects of HIV on the brain.

What is neurocognitive impairment?

The term cognition refers to the high-level functions of the brain, such as speaking, seeing, calculating, processing information, remembering and problem-solving. When these processes are reduced, experts call this neurocognitive impairment (or NCI).

The symptoms of NCI that can affect people living with HIV include:

  • confusion
  • thinking that is foggier or less clear
  • difficulty finding words
  • difficulty with fine motor skills, coordination and concentration—for example, difficulty with a task like handwriting and needing to concentrate to write legibly
  • loss of short- and long-term memory—for example, trouble remembering appointments and names
  • diminished capacity for planning, processing information and problem-solving
  • apathy and lack of motivation
  • personality changes
  • difficulty with multi-tasking

Fumbling for words and drawing a blank when you talk to somebody can make you feel frustrated, embarrassed and anxious. This, in turn, may make you want to avoid potentially embarrassing situations.

The symptoms of NCI can range from being so mild that they are barely noticeable to so severe they interfere with a person’s relationships, activities and day-to-day life. Some people living with HIV experience symptoms of NCI while others live with HIV for decades and experience no cognitive problems whatsoever.

Different types of NCI that affect people with HIV

When talking about NCI among people with HIV, experts often speak of HIV-associated neurocognitive disorders (HAND). This umbrella term covers a range of disorders:

  • Asymptomatic neurocognitive impairment—Neuropsychological tests reveal subtle signs of impairment but a person’s functioning and day-to-day life don’t seem to be affected.
  • Mild neurocognitive impairment—There are signs of impairment in both neuropsychological tests and daily living.
  • HIV-associated dementia—The most severe and rarest form of neurocognitive disorder. Dementia is a general term that refers to a severe decline in cognitive function that interferes with daily activities. It is not a disease itself but, rather, a group of symptoms that may accompany a disease or condition. 

How common is NCI among people living with HIV?

Experts are still not exactly sure how prevalent NCI is among people living with HIV. Since the advent of highly active antiretroviral therapy, rates of the most severe form of NCI, HIV-associated dementia, have declined dramatically in the developed world, from about 10 to 15% down to as low as 1 or 2%. However, milder forms of NCI seem to be more common. The results of one study, released in the summer of 2009, indicate that the rate of NCI was 52% among 1,555 middle-aged HIV-positive participants—with 21% having mild impairment; 29%, moderate impairment; and 2%, severe impairment. There is not yet a consensus on these data, but it is clear that NCI—especially its milder and more moderate forms—may be touching a large proportion of people living with HIV.

NCI is more common among some groups of people living with HIV, for example, those who have more advanced HIV, diabetes or hepatitis C. Age can also be a factor: cognitive impairments are more prevalent among people living with HIV who are over 50 than among those under 40.

What causes NCI in people living with HIV?

HIV enters the brain early on in the course of infection. Although it doesn’t infect brain nerve cells (neurons), HIV damages them both directly and indirectly. Proteins from HIV-infected cells cause the release of certain chemical messengers (neurotransmitters), which, in turn, cause inflammation, excitation and even cell death. HIV also infects other cells in the brain, which causes a release of toxins that damage the brain.

While HIV-associated dementia, which is associated with advanced HIV, may be caused by the direct toxicity of HIV in the brain, milder forms of NCI may be the result of secondary processes brought on by a low-level presence of the virus. HIV-associated dementia can result from uncontrolled viral replication and immune suppression, so when viral replication is controlled with HAART, rates of HIV-associated dementia drop. But low-grade infection and inflammation may subtly affect the neurons and cause mild neurocognitive disorder.

In addition to HIV, many other factors can cause or contribute to NCI, including aging; depression; a concussion; learning disabilities; alcohol consumption; the use of illicit drugs, such as cocaine, crystal meth, heroine, ecstasy, LSD and inhalants; neurological conditions, such as epilepsy and multiple sclerosis; conditions such as high blood pressure, diabetes, asthma, thyroid disease and hepatitis C; and vitamin B1 and B12 deficiencies.

Aging and NCI

Aging can also affect the structure and function of the brain—slowing it down, making it less accurate, and reducing its capacity to store and retrieve memories. For the growing number of older men and women living with HIV, both aging and HIV can affect the mind.

Like cognitive problems that result from HIV, age-related cognitive decline can range from mild to severe:

  • Age-related cognitive decline—Normal decline associated with aging.
  • Mild cognitive impairment—Decline in memory and performance on neuropsychological testing; seen in about 20% of those over 70.
  • Dementia—The most severe impairment, a common cause of which is Alzheimer’s disease. This irreversible illness severely and progressively affects a person’s cognition, behaviour, motor functions and day-to-day living. Most often found in people over 65, its incidence doubles about every five years from then. (Approximately 50% of HIV-negative people over 80 have Alzheimer’s.)

For years, doctors and people living with HIV have suspected that HIV causes accelerated aging of the body. It wouldn’t be surprising if the virus had this effect on the brain too. In a small study, the blood flow in the brains of people living with HIV appeared similar to that of HIV-negative people who were 15 to 20 years older.

If you suspect that you have an HIV-associated neurocognitive disorder…

If you have HIV and suspect that you have a problem with your cognition, the first step is to see your doctor. He or she may refer you to a specialist for testing. Diagnosing an HIV-related neurocognitive disorder involves testing to evaluate the functioning of different parts of the brain. If you have signs of mild neurocognitive disorder, your doctor will take a full history and perform further tests to determine what might be causing the impairment.

Anti-HIV drugs

There is now clear evidence that it is important to start anti-HIV drugs before you get sick. Current recommendations suggest starting before your CD4 count falls to 350, to keep your immune system strong and protect your overall health. Some researchers think that early intervention with anti-HIV medications may also reduce the risk of HIV-associated neurocognitive disorders and decrease symptoms. It is not yet clear whether HIV-associated neurocognitive disorder, even if it is affecting daily functioning, should be enough of a reason to start treatment.

Some anti-HIV drugs are better than others at passing through the blood–brain barrier, which keeps many toxins out of the brain and spinal cord. Recent studies indicate that having a regimen with more drugs that can penetrate the barrier may lead to reduced rates of neurocognitive impairment.

A group of researchers has developed a system of ranking the ability of anti-HIV drugs to penetrate the blood–brain barrier (see chart below). However, there are no official guidelines that indicate whether or not to change a HAART regimen if you have an undetectable viral load but are showing signs of neurocognitive impairment. That is a decision for you and your doctor.

Penetration of anti-HIV drugs through the blood-brain barrier
  Much above average Above average Average Below average
Nukes (NRTIs) AZT abacavir
FTC
ddI
3TC
d4T
tenofovir
Non-nukes (NNRTIs) nevirapine efavirenz etravirine  
Protease inhibitors (PIs) boosted indinavir boosted darunavir
boosted fosamprenavir
indinavir
boosted lopinavir
atazanavir
boosted atazanavir
fosamprenavir
nelfinavir
ritonavir
saquinavir
boosted saquinavir
boosted tipranavir
Integrase inhibitor   raltegravir    
Entry/fusion inhibitor   maraviroc   T-20
Adapted from Letendre SL et al, 17th CROI, 2010, Abstract 172

Nutrition and lifestyle

Research has shown that what’s good for your heart is good for your brain. A diet and lifestyle that promote the health of your heart also benefit your brain. These include:

  • a diet rich in fruit and vegetables, soy, fish and whole grains, and low in fat, salt, caffeine and alcohol
  • regular exercise
  • stress management
  • no smoking
  • getting plenty of sleep

Your brain relies on healthy arteries, which carry blood to the brain. As inflammation plays a key role in the processes that block and damage arteries, consuming plenty of natural anti-inflammatories may promote your brain health. This means avoiding fats that promote inflammation, such as partially hydrogenated oils (“trans fats”) and polyunsaturated vegetable oils. And it means eating anti-inflammatory foods and seasonings, such as ginger, turmeric, colourful berries, grapes, citrus fruits, foods rich in omega-3 fatty acids (such as wild fatty fish, flaxseed and walnuts) and garlic (eating more than a couple of cloves of raw garlic per day may interact with some drugs, so speak with your doctor and pharmacist about possible interactions with your medications).

There is also some evidence to suggest that the impaired cognitive function experienced by some people with HIV may result from a vitamin B12 deficiency. Not getting enough vitamin B12 can cause memory loss, confusion, chronic fatigue, decreased reflexes, unsteady gait, weakness, neuropathy and depression. Vitamin B12 deficiency is common among people living with HIV and older adults. Unfortunately, the tests commonly used to assess a person’s B12 status may not be reliable—they often indicate that a person has a “normal” level when, in fact, there is a deficiency. Consequently, vitamin B12 therapy based on symptoms, rather than test results, is recommended.

Talk to your doctor or a dietitian about ways to ensure that you’re getting enough vitamin B12 and that your diet and lifestyle are heart- and brain-healthy.

Physical exercise

A number of studies of sedentary (or physically inactive) seniors who participated in fitness programs showed that exercise improved their cognition. Exercise may promote the growth of brain cells and increase the amount of human growth hormone that your body produces, which, in turn, can improve your memory and capacity to learn. An active lifestyle might prevent or delay the loss of cognitive function.

Exercise is important, especially if you’re HIV-positive, because it can also prevent and help many conditions, including diabetes, high blood pressure, chronic kidney disease and depression, all of which may negatively affect cognition. Resistance exercises, such as aerobic exercise and weight-lifting, are particularly beneficial. Learning ballroom dancing may be good not only because of the physical exercise and social interaction but also because of the mental benefits.

Fitness for the brain

Until recently, scientists believed that that our brains were fixed, or “hard-wired.” We now know that the brain has the capacity to change its structure, be rewired and rehabilitated, to overcome a wide range of problems. The brain is malleable, or plastic, and can change based on what we do and think. Neuroscientists sometimes use the line “use it or lose it”; the upside of this is that there is much we can do to maintain and even improve the health of our brains.

In the same way that physical exercises can strengthen your body, the right kind of brain exercises can strengthen your mind. See the “Brain Exercise” box below for examples. There are also computer-based programs that claim to improve brain function. Before spending money on one of these, it is important to verify that the claims made by the program’s makers are supported by research. For example, the Brain Fitness Program has been tested by researchers from the Mayo Clinic and the University of California in a study called the IMPACT (Improvement in Memory with Plasticity-based Adaptive Cognitive Training) study. The program proved successful at dramatically improving the memory, brain processing speed and neuropsychological test performance of healthy HIV-negative seniors. (For more information about the Brain Fitness Program, read “A Mind of Her Own” in the Winter 2010 issue of The Positive Side.)

Brain exercise

Learning new things is highly valuable when it comes to your brain health. The best activities are progressively challenging, mentally rewarding, novel or surprising, and demand focused attention. Here are some of the best ways to exercise your brain:

  • Learn to play music.
  • Learn another language.
  • Do crossword puzzles (must be challenging) or jigsaw puzzles (more than 500 pieces).
  • Play ball or juggle.
  • Crochet or knit.
  • Use your “other” hand.
  • Play bridge.
  • Learn a new physical activity that requires concentration, for example, take dance lessons.

Strategies for managing symptoms

If you suspect you may have NCI, your doctor can also refer you to a rehabilitation expert, for example, a physical therapist or an occupational therapist, who can help you deal with the effects of NCI on your daily functioning. Which strategies are right for you will depend on your needs and goals; however, these are some general tips that may help:

  • Create a routine—For example, always put your keys in the same place; associate taking your meds with certain things, like getting up in the morning; and plan to do recurring activities on the same day of the week.
  • Use memory aids—If you’re a visual person, use visual reminders like “sticky” notes; if you’re more of an auditory person, you may find a timer or an alarm helpful.
  • Minimize distractions—Turn the TV or radio off when you’re talking to someone or busy with another task. This will help you focus better.  
  • Pace yourself—Try to spread activities out throughout the week so you’re not doing everything at once. And leave yourself more than enough time to do things.
  • Use personal organizers—An electronic calendar, cell phone or other kind of personal organizer may help make your life easier. Create lists you can refer to.

 

Acknowledgement

This fact sheet is based on an article originally published in The Positive Side (Winter 2010, Volume 11 Issue 2). We thank Maggie Atkinson, an AIDS activist, lawyer and long-term survivor with HIV/AIDS, for writing the original article.

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Author(s): Atkinson M, McLay D, Koenig D

Published: 2011