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Good News About HIV and the Aging Brain

November/December 2011

Many studies of HIV's impact on the brain have been conducted since 1996 when ART became widely available in high-income countries. In these studies, researchers have enrolled HIV-positive people who had serious symptoms, such as AIDS, arising from a weakened immune system. It is therefore possible that such studies produced a skewed profile of the impact of HIV infection on the brain, perhaps portraying excessive damage.

To uncover what HIV does to the brain, it is important to study a wide variety of people, including people with HIV who have not had serious symptoms such as those seen in AIDS. Two studies have focused on HIV-positive people who have minimal symptoms of disease. One suggested that the rate of neurocognitive impairment in symptom-free HIV-positive people is not different from that of HIV-negative people. Another study suggested that mild neurocognitive impairment is relatively common among symptom-free people. As a result of these conflicting results, some neuroscientists argue that it is not certain whether HIV can cause deterioration in neurocognitive ability among "medically stable" people who are free from HIV-related symptoms.


Age or AIDS?

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An additional concern faced when trying to assess neurocognitive impairment is the effect of aging. Some researchers suspect that the natural process of aging may intensify HIV's impact on the brain, and vice versa. Studies exploring this issue have produced mixed results.

In part, this mix of results arises from the confounding impact of co-morbidities in some older people, including depression, substance and alcohol abuse, cardiovascular disease and diabetes.

Researchers at King's College in London, UK, have conducted extensive neurocognitive assessments as well as MRI scans on 95 volunteers, some of whom were HIV positive. The researchers described the HIV-positive people as "medically stable." By this, they meant that not only were participants symptom free but that they were taking ART, had very low viral loads and relatively high CD4+ cell counts, and did not have a history of substance use or serious mental health issues.

The King's College team concluded that "HIV disease by itself does not significantly impair cognitive functions when patients are [free from symptoms of HIV disease and are medically stable]."


Study Details

Researchers enrolled 95 gay and bisexual men. They were divided into the following four groups:

  • HIV-positive men aged 20 to 40 years
  • HIV-negative men aged 20 to 40 years
  • HIV-positive men aged 50 to 75 years
  • HIV-negative men aged 50 to 75 years

The health information gathered from each HIV-positive man was matched to that from an HIV-negative man of similar age and educational background.

Researchers did not enroll anyone who had any of the following diagnoses:

  • AIDS-related infections that affected the brain
  • hepatitis B or C viruses
  • neurologic disorders
  • a history of harmful substance use (including alcohol)
  • any chronic cardiac, liver or kidney problems that could affect neurocognitive abilities
  • moderate-to-severe psychiatric disorders

Researchers conducted extensive neurocognitive assessments, and blood tests were done to screen for many infections and conditions that could have an impact on neurocognitive assessments, such as diabetes, untreated thyroid disease and so on. High-resolution MRI scans were also done.


Results -- HIV and Age

People with HIV infection did not have impaired neurocognitive function compared to HIV-negative people. HIV infection did not heighten age-related decline in neurocognitive function.

The researchers found that, in general, older people compared to younger people had some neurocognitive impairment, particularly affecting memory. This was considered a normal consequence of aging by the researchers.


Results -- MRI Scans

High-resolution scans detected changes in some regions of the brains of older participants. Again, these were considered a normal consequence of the aging process.

HIV-positive people had slightly reduced gray matter in one part of the brain, the frontal gyrus.


Making Sense of the Findings

The London researchers found that "in general, there was no significant [neurocognitive] impairment in our stable HIV-1 patient group." Furthermore, they stated that their findings "suggest that stable HIV-1 [symptom-free] participants with long-term suppression of viral load and CD4+ counts above 200 cells do not necessarily show cognitive decline."

The London team also states that previous studies that found neurocognitive impairment in HIV-positive people may not have taken into account factors such as alcohol and substance use, psychiatric conditions and other medical conditions.

According to the study team, in the present study participants had relatively high IQs and were in "good medical and psychiatric health." The researchers suggest that it is possible that that these factors may have played a role in protecting the men from neurocognitive degeneration.

Long-term studies are needed in order to learn what happens to such stable men as they age with HIV. Also, future studies need to include a broader range of HIV-positive people, including women.

If the results from the London study are confirmed, then dealing with co-morbidities that affect cognition (such as alcohol and substance use, metabolic problems such as diabetes and co-infections such as hepatitis C virus) may become more important to help reduce their impact on the brain.


References

  1. Thompson PM, Dutton RA, Hayashi KM, et al. Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4+ T lymphocyte decline. Proceedings of the National Academy of Sciences USA. 2005 Oct 25;102(43):15647-52.
  2. 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.
  3. Towgood KJ, Pitkanen M, Kulasegaram R, et al. Mapping the brain in younger and older asymptomatic HIV-1 men: Frontal volume changes in the absence of other cortical or diffusion tensor abnormalities. Cortex. 2011; in press.


  
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This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication TreatmentUpdate. Visit CATIE's Web site to find out more about their activities, publications and services.
 
See Also
More Research on Aging and HIV

Reader Comments:

Comment by: Michael Buitron (Long Beach, CA) Fri., Feb. 24, 2012 at 1:59 am EST
I worked on a similar longitudinal study that enrolled more than gay men. As far as leaving out the "middle group," think of someone doing a study comparing the health effects of being tall vs being short. If you enroll average height people, subtle differences disappear and it becomes almost impossible to tease out the differences between young and old brains.

Unfortunately this study seems to have run into similar problems to the one I worked on. If you control for too many co-morbidities, you wind up with a lot of well-educated upper and middle income gay white men who exercise regularly, eat well, and don't really represent the real face of AIDS today. The things that put people at risk for HIV--mental health issues, drug addiction, STDs, homelessness, poor self esteem, poor education, unemployment and underemployment, and more--also can negatively impact cognitive function.

In real life, those of us with HIV don't match healthy negative controls. From my experience of sifting through study data and knowing that HIV gets in the brain much more easily than HIV drugs, HIV probably exacerbates cognitive decline in an aging positive population. If we expect to improve brain function, we need to treat the obesity, Hep-C, and drug addiction that excluded participation in this study.
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Comment by: Dave B. (Auburn Al) Thu., Feb. 23, 2012 at 3:07 pm EST
I know this study was an icebreaker in the context of an important studay involving those with HIV and the possibility of HIV causing brain degeneration, but what I can not for the life of me figure out is why skip the age group between 41 and 49. This group, if affected, may show symptoms that progressively get worse by the time an individual reaches their 50's, providing they live that long. I think another study, this one in the US, should be conducted, and the study groups broken down into either smaller groups or groups that are more inclusive.
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Comment by: William W. (Salt Lake City, Utah) Thu., Feb. 23, 2012 at 2:24 pm EST
One perspective study one "suggestive" result does not make for consensus and in this regard the jury is still out and will be out for some time as the NIH is solicitating applications for grants to study this and other aspects of HIV persistence in the CNS and other reservoirs. Recent studies have revealed 1) poor drug penetration in these compartments and 2) discordant HIV Viral levels relative to plasma concentrations.
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