Research takes close look at HIV's impact on brain of aging patients

Imaging shows reduced blood flow

Research consistently has shown that HIV-positive patients perform cognitively at lower levels than their uninfected peers, an expert says.

"Some studies have looked at aging and cognitive performance and found that when compared with other patients, a 55-year-old HIV positive person with zero to four years of infection was equal to a 65-year-old HIV negative person," says Beau Ances, MD, PhD, assistant professor of neurology at Washington University in St. Louis.

However, the physiology of this difference has been less studied. Ances and co-investigators sought to find a noninvasive way to compare brain function in HIV positive people to HIV negative people.

The research led to the finding that at any given age the baseline cerebral blood flow value for HIV-positive subjects were equivalent to those for HIV-negative subjects who were 15 years older.1

"I was very interested in a technique I've been working on to measure blood flow in the brain," Ances says. "We tag red blood cells in the neck and wait a period of time and then measure how many tagged at the neck reached a certain slab of the brain."

This process can be done without an injection, he says.

The study performed imaging on a 3 Tesla whole-body system using an 8-channel receive head coil. Then researchers used an inversion recovery prepared 3-dimensional fast spoiled pulse sequence to obtain high-resolution structural images.1

"We excited the molecules in the neck and waited for them to get to the brain," Ances explained. "Then we measured how much blood flow is going to the brain."

It's known that as people age their blood flow decreases, partially due to arteriosclerosis, vessels that are less spongy, strokes, and other factors, he notes.

Comparing HIV-positive to HIV-negative subjects, the study found that HIV-positive people had the blood flow of HIV-negative people years and sometimes decades older.

Study inclusion/exclusion criteria had people screened for a clear-cut medication use status. That is, subjects either had not been taking medications for at least a few months, or they had been on medication for at least three months, Ances says.

Their findings suggested that antiretroviral therapy helps to restore blood flow, but not to the extent of people who are HIV negative, he says.

"It could mean that medications give them a boost and make things better, but after time they go down again," Ances explains. "You don't get back to your baseline of what a person should be for that age."

This research suggests that HIV clinicians have yet another reason to start HIV positive patients earlier on their medication therapy, particularly if they already are middle-aged or older.

"We make the decision about when to start therapy dependent on patients' CD4 cell count and viral load, and we don't look at what happens in the brain," Ances says. "But within days of infection the virus already is in the brain, and it stays in the brain for the rest of that person's life."

The study shows that even a 20-year-old with HIV infection already has an impact on blood flow to the brain, so maybe this issue should be a consideration in therapy decisions, he suggests.

"What these results are suggesting is we have a marker here to evaluate patients," Ances says.

If HIV-positive patients have signs of cognitive decline then clinicians should ask whether they will need to be treated with neuroprotective medications or start on ARTs sooner, he says.

There are no definitive answers, but these questions need to be investigated, he adds.

At the very least, HIV clinicians should acknowledge their patients' cognitive complaints and let them know that this is an impact of the disease, Ances says.

"I have a large number of older patients who say, 'My thinking is not right. What's going on with me?'" he says. "The answer is, 'Yes, your brain is not right. We may need to consider other medication.'"

With the nation's aging population of HIV patients, clinicians might find that it is difficult to identify whether cognitive decline is due to their HIV infection or Alzheimer's disease or some other forms of dementia.

But there is some pathological research that suggests some of the factors leading to cognitive decline are similar between Alzheimer's disease and the way the brain is impacted by HIV infection, Ances says.

"There might be a common mechanism of aging the brain," he says.

There are no medical solutions to these kinds of cognitive decline, but HIV clinicians can give their patients general advice that will improve their overall health, including mental health.

"I tell patients, 'If you don't use it, you'll lose it,'" Ances says.

Education and exercise are neuroprotective, he says.

"I tell all my patients, 'Stop sitting in front of the TV; stay active and physically fit, and this is very important: try to walk and do things,'" he adds. "If they do this it will help their brain function, their heart function, bones, and everything."

Reference

  1. Ances BM, Vaida F, Yeh MJ, et al. HIV infection and aging independently affect brain function as measured by functional magnetic resonance imaging. JID. 2010;201:336-340.