Fat marker predicts cognitive decline in people with HIV

Johns Hopkins scientists have found that levels of certain fats found in cerebral spinal fluid can predict which patients with HIV are more likely to become intellectually impaired.

The researchers believe that these fat markers reflect disease-associated changes in how the brain metabolizes these fat molecules. These changes disrupt the ' ability to regulate the activity of cells' "garbage disposals" meant to degrade and flush the brain of molecular debris. In this case, too much cholesterol and a fat known as sphingomyelin build up in the lysosomes—the garbage disposals—backing up waste and leading to often debilitating cognitive declines.

As many as half of patients infected with HIV will develop some form of , ranging from mild (trouble counting change or driving a car) to frank dementia (an inability to manage activities of every day life), but no tests have been available to predict which people were more likely to suffer cognitive losses.

"Every researcher of neurodegenerative disease is chasing biomarkers for the same reason: It's better to identify problems before they strike," says Norman J. Haughey, Ph.D., an associate professor in the departments of neurology and psychiatry and at the Johns Hopkins University School of Medicine. He led the current study described online in the journal Neurology.

"It's very hard to reverse after it starts," he says. "Instead, we want to figure out who is likely to lose cognitive function and stop the damage before it happens."

Haughey and his team analyzed 524 samples collected from seven test sites across the continental United States, Hawaii and Puerto Rico. The samples came from 291 HIV-positive participants and 30 HIV-negative subjects. The investigators found that early accumulations of a small number of these fat molecules could predict the probability of . As cognitive function declined in these patients, the number of different types of fat molecules that accumulated increased. The types of accumulating in HIV were very similar to those that accumulate in inherited forms of a class of diseases called lysosomal storage disorders. This suggests that in some HIV-infected patients, the brain is retaining more of these fats, and this may disrupt the function of lysosomes.

Haughey says he believes some of these impairments in the metabolism of these fats found in people with HIV stems from the infection itself, while others may be linked to the lifesaving antiretroviral therapy taken by most people with HIV. The medications have been associated with elevated blood cholesterol and triglycerides, along with a host of other side effects. Those with HIV are now taking these drugs for decades and the complications from long-term use have not been well studied, he says.

The similarities between the metabolic disturbances in HIV-infected individuals and those apparent in lysosomal storage disorders are enabling Haughey and his team to collaborate with researchers who study genetic lysosomal storage diseases, and who are developing experimental treatments to clear the fat buildup. They are currently exploring dietary and pharmacological interventions designed to restore balance that could potentially restore brain metabolism in HIV-infected individuals, and in doing so could promote good brain health by ensuring the function properly.

add to favorites email to friend print save as pdf

Related Stories

Popular HIV drug may cause memory declines

Sep 27, 2012

The way the body metabolizes a commonly prescribed anti-retroviral drug that is used long term by patients infected with HIV may contribute to cognitive impairment by damaging nerve cells, a new Johns Hopkins research suggests.

More pediatric HIV patients on antiretroviral therapy

Aug 27, 2013

(HealthDay)—The proportion of perinatally HIV (PHIV)-infected youth on antiretroviral therapy (ART) has increased, leading to decreases in rates of viremia and advanced immunosuppression in recent years, ...

Recommended for you

Intimacy a strong motivator for PrEP HIV prevention

Aug 19, 2014

Men in steady same-sex relationships where both partners are HIV negative will often forgo condoms out of a desire to preserve intimacy, even if they also have sex outside the relationship. But the risk of ...

UNL sociologist studies HIV spread in rural Puerto Rico

Aug 14, 2014

Puerto Rico has one of the highest HIV rates in the United States, primarily from drug users sharing needles. To help prevent HIV infections, a University of Nebraska-Lincoln sociologist is using his expertise ...

User comments