HIV Speeds Brain Aging

Janis C. Kelly

January 30, 2010

January 30, 2010 — Patients infected with human immunodeficiency virus (HIV) lose brain functional abilities 15 to 20 years prematurely probably because of either HIV infection itself or the treatments used to control it, researchers at Washington University School of Medicine in St. Louis, Missouri, and the University of California, San Diego, have found.

Blood flow in the brains of HIV patients is reduced to levels normally seen in much older subjects, scientists report online in the February 1 issue of the Journal of Infectious Diseases. Fortunately, there appears to be no synergistic interaction between HIV serostatus and age.

"The graying of the AIDS patient community makes this infection's effects on the brain a significant source of concern," lead investigator author Beau Ances, MD, PhD, said. Dr. Ances, who is assistant professor of neurology at Washington University, added, "Patients are surviving into their senior years, and a number of them are coming forward to express concerns about problems they're having with memory and other cognitive functions."

Grays With AIDS

Currently, 14% to 18% of all US AIDS patients are older than 50 years. This age group also has one of the highest rates of new infection. The researchers note that if current trends continue, by the year 2015, more than half of the AIDS patient population will be older than 50 years.

Prior studies of HIV infection's long-term health effects have found that the virus may adversely affect the heart, liver, endocrine system, skeleton, and kidney, but this is the first study to use brain imaging to study interactions between aging and HIV. A recent study of the overall health of the body found that HIV infection advances the body's age by about 10 years. HIV can lead to dementia in some patients, but scientifically quantifying the effects of HIV and aging in the brain has been challenging, according to Dr. Ances.

"We believe the virus crosses into the brain using infected immune cells," Dr. Ances said. "Once in the brain, HIV doesn't directly infect neurons but instead affects supporting cells that can release immune factors that harm neurons." This continued immunologic challenge depletes resources and triggers increased metabolic demands, which show up as greater changes in cerebral blood flow in HIV-positive subjects, as well as in changes in the functional blood oxygen level–dependent signal.

“We were surprised that the brain is affected by the same amount as the body,” Dr. Ances told Medscape Neurology. “Usually the brain is protected from insults. However, this work is in line with others that have shown that HIV leads to increase in frailty that is not just specific to, say, the liver or the bones but also the brain. It raises a lot of new questions of how we can protect the brain, when should we start meds, and whether we should start neuroprotective meds earlier.”

Brain Blood Flow Lower, Less Responsive in HIV

The researchers used functional magnetic resonance imaging to assess brain blood flow in 26 subjects with HIV and 25 uninfected controls. Both groups were comparable in mean age range and education, and researchers screened participants for confounding factors, such as head injuries, neuropsychiatric disorders, and substance abuse.

When individuals were resting in the scanner, brain blood flow values were significantly reduced in subjects with HIV compared with uninfected controls. These reductions decreased brain blood flow to levels roughly equivalent to readings seen among uninfected individuals 15 to 20 years older.

When scientists asked participants to perform a visual task, which normally triggers an increase in blood flow to particular regions of the brain involved, participants with HIV had greater blood flow increases, suggesting that the brain and its support systems had to work harder to get the task done.

Researchers also found that HIV reduced brain blood flow even among young, recently infected patients, reinforcing earlier results that this group has previously published.

Virus, Medications, or Both May Affect Brain Function

Steven G. Deeks, MD, professor of medicine at the University of California, San Francisco, and a faculty member in the Positive Health Program (AIDS Program) at San Francisco General Hospital. was asked by Medscape Neurology to comment on the study.

“The major limitation [of the study] is likely to be the fact that it is nearly impossible to truly match HIV-infected persons with uninfected persons, as those who acquire HIV are invariably different than those who do not acquire HIV. The small sample size here makes it possible (and even likely) that other factors may have compounded their observations,” Dr. Deeks said.

“I find the neurology of aging to be far more complex and controversial that the other organ systems that may be affected by HIV,” Dr. Deeks added.

"Brain blood flow levels decline naturally as we age, but HIV, the medications we use to control it, or some combination of the 2 appear to be accelerating this process independent of aging," Dr. Ances said.

“The HIV community is graying as they are now living longer with the virus due to medications. The question is what are the new challenges that we will see with HIV patients getting older? Does HIV accelerate aging? Do these medications have toxic effects? We need to longitudinally follow patients to see the effects of medications. It may be that the drugs are beneficial but could be toxic to the brain for long periods of time. It could be that these meds do not lead to a free lunch.”

According to Dr. Ances, similar mechanisms of amyloid deposition have been seen in Alzheimer's disease and HIV, and they may have common pathways.

The study was funded by the Dana Foundation, the National Institutes of Health, the HIV Neurobehavioral Research Center, and the University of California, San Diego, AIDS Research Center. Dr. Ances and Dr. Deeks have disclosed no relevant financial relationships.

J Infect Dis. 2010;201:336-340.


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