6 November 2012 

Pilot study of brain training exercises—promising but limited results

The widespread availability of potent combination therapy (commonly called ART or HAART) for HIV has led to greatly improved health and survival for HIV-positive people in Canada and other high-income countries who can adhere to therapy.

Although ART has many benefits, it does not entirely suppress the inflammation that is incited by chronic HIV infection. Researchers are concerned that prolonged exposure to such inflammation could have an effect on many organ-systems, including the brain, particularly as HIV-positive people age.

In the time before HAART became available, HIV could cause serious impairment of intellectual functioning as well as problems with movement, muscle control, reflexes and other related issues. However, in the current era, thanks to ART, such severe HIV-related problems are uncommon. Instead, research teams have reported that mild neurocognitive impairment appears to be relatively common.

Neurocognitive dysfunction can degrade a person’s quality of life and reduce their overall potential. A decline in neurocognitive abilities could affect the speed at which information is processed in the brain. Reduced processing speed could have the following potential impacts on HIV-positive people:

  • affect their ability to take ART and other medicines exactly as prescribed (adherence)
  • reduce their ability to manage their finances
  • weaken their attention span, which could affect their ability to read, learn and drive safely

Researchers have found that reduced processing speed and other impairments in neurocognitive functioning also occur in older HIV-negative adults. Aging specialists (gerontologists) have developed brain-training exercises to help these adults. Such exercises are generally computer-based game-related activities that stimulate different parts of the brain and have been found to do the following in experiments with older HIV-negative people:

  • improve performance of everyday tasks
  • improve driving safety and significantly reduce car crashes in simulated tests

In at least one study, HIV-negative people who have done brain-training exercises reported better overall health, improved neurocognitive function and seem to be at reduced risk of depression.

Spurred by these promising results, a research team at the University of Alabama that included specialists in geriatric medicine, dementia and psychology conducted a pilot study of one package of brain-training exercises in 22 middle-aged HIV-positive people and compared their subsequent neurocognitive performance to that of 24 other middle-aged HIV-positive people who did not receive brain training.

Results of neurocognitive testing showed that after 10 hours of limited brain-training exercises done over a period of five weeks, participants had faster information processing. Bear in mind that this was a pilot study and although the results appear promising, there are many issues that need to be explored and resolved with regard to brain-training exercises in HIV-positive people.

Study details

Researchers carefully screened and recruited HIV-positive people without mental health conditions, brain trauma or any history of neurological damage.

The average profile of 46 participants was as follows:

  • 74% men, 26% women
  • age – 52 years
  • CD4+ count – 450 cells
  • proportion prescribed ART – 95%
  • proportion with an HIV viral load less than 50 copies/ml – 30%

Researchers randomly assigned participants to one of the following two groups:

  • 22 participants entered the brain-training group
  • 24 participants acted as a control or comparison group and did not receive brain training

Once randomized, participants returned to the study centre and were told how to do the brain-training exercises. The 10 hours of brain training could be done over a period of several weeks.

Participants used a program called Insight, made by the Posit Science Company. They used games that were designed to speed up information processing.

All participants were interviewed at the start and at the end of the study and at both time points underwent neurocognitive testing.

Those participants who did not receive brain training were contacted five weeks after randomization to schedule neurocognitive testing.


At the start of the study, there were no significant differences between study groups.

Researchers found that participants who underwent brain training showed improved ability to carry out everyday activities. However, improvements to higher brain functions such as those involving planning, memory, reasoning ability and problem solving did not occur. Yet, when interviewed on completion of brain-training exercises, participants felt that they experienced improvements in the following areas:

  • overall mental ability
  • memory
  • speed of information processing
  • ability to focus

Bear in mind

  1. The results from this pilot study are encouraging; however, it was just a pilot study.
  2. Only one neurocognitive aspect—speed of information processing—was targeted by the brain-training exercises.
  3. Although ART was prescribed to 95% of participants in the present study, rates of response to therapy were relatively low, as judged by the proportion (30%) of participants who had a viral load less than 50 copies/ml.

It is likely that HIV-positive people who are working in demanding fields and whose work requires analytic abilities and higher mental functions may be better served by exercises that are designed to focus on a variety of neurocognitive functions, including the following areas:

  • memory
  • reasoning
  • vocabulary
  • numeracy

Moving forward

In the future, other studies should consider these issues when researching brain training in HIV-positive people:

  • confirm the present study’s findings
  • assess how long the benefits of such brain-training exercises last
  • determine how much brain training people need
  • use more sophisticated and complex brain-training exercises so that higher intellectual functions can be restored, maintained or improved
  • compare the effects of different brain-training software on HIV-positive people
  • explore whether specific combinations of anti-HIV drugs affect the response to brain training

The Alabama research team stated that other interventions might also be useful for improving neurocognitive functioning in HIV-positive adults, specifically these:

  • physical exercise
  • intellectual stimulation
  • improved nutrition
  • better sleep hygiene
  • reduced alcohol and substance use
  • treatment of depression and other mental health issues

However, the researchers noted that these interventions also require testing to assess their impact on HIV-positive people’s neurocognitive abilities.


                                                                                                            —Sean R. Hosein


  1. Vance DE, Wadley VG, Crowe MG, et al. Cognitive and Everyday Functioning in Older and Younger Adults with and without HIV. Clinical Gerontologist. 2011 Oct;34(5):413-426.
  2. Vance DE, Fazeli PL, Ross LA, et al. Speed of processing training with middle-age and older adults with HIV: a pilot study. Journal of the Association of Nurses in AIDS Care. 2012 Nov;23(6):500-10.
  3. Appay V, Sauce D. Immune activation and inflammation in HIV-1 infection: cause and consequences. Journal of Pathology. 2008 Jan;214(2):231-41.
  4. Gendelman HE, Zheng J, Coulter CL, et al. Suppression of inflammatory neurotoxins by highly active antiretroviral therapy in human immunodeficiency virus-associated dementia. Journal of Infectious Diseases. 1998 Oct;178(4):1000-7.
  5. Harezlak J, Buchthal S, Taylor M, et al. Persistence of HIV-associated cognitive impairment, inflammation, and neuronal injury in era of highly active antiretroviral treatment. AIDS. 2011 Mar 13;25(5):625-33.
  6. Griffin ÉW, Mullally S, Foley C, et al. Aerobic exercise improves hippocampal function and increases BDNF in the serum of young adult males. Physiology & Behavior. 2011 Oct 24;104(5):934-41.
  7. Fabbiani M, Ciccarelli N, Tana M, et al. Cardiovascular risk factors and carotid intima-media thickness are associated with lower cognitive performance in HIV-infected patients. HIV Medicine. 2012; in press.
  8. McCrimmon RJ, Ryan CM, Frier BM. Diabetes and cognitive dysfunction. Lancet. 2012 Jun 16;379(9833):2291-9.
  9. Peters R. Blood pressure, smoking and alcohol use, association with vascular dementia. Experimental Gerontology. 2012; in press.
  10. Igase M, Kohara K, Miki T, et al. The association between hypertension and dementia in the elderly. International Journal of Hypertension. 2012;2012:320648.
  11. White WB, Wolfson L, Wakefield DB, et al. Average daily blood pressure, not office blood pressure, is associated with progression of cerebrovascular disease and cognitive decline in older people. Circulation. 2011 Nov 22;124(21):2312-9.
  12. Yaffe K, Lindquist K, Schwartz AV, et al. Advanced glycation end product level, diabetes, and accelerated cognitive aging. Neurology. 2011 Oct 4;77(14):1351-6.
  13. Heaton RK, Clifford DB, Franklin DR Jr., et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology. 2010 Dec 7;75(23):2087-96.