Jim Kling

March 16, 2012

March 16, 2012 (Seattle, Washington) — Central obesity might be a contributing factor to neurocognitive impairment (NCI) in HIV-positive individuals, according to research presented here at the 19th Conference on Retroviruses and Opportunistic Infections.

Both central obesity and diabetes have been linked to NCI in people uninfected with HIV, and some protease inhibitors can lead to an increase in central obesity.

"We knew that HIV was causing people to lose weight peripherally and gain it centrally, and that cholesterol and other blood lipids go up in a dangerous way for heart disease. What no one had done was ask: If you have cardiovascular disease, do you also have cerebrovascular disease?" Allen McCutchan, MD, professor of medicine at the University of California at San Diego, who presented the research, told Medscape Medical News.

The researchers conducted a study of HIV-associated neurocognitive disorders in 1578 patients in the CHARTER prospective trial. Of these, 130 HIV-positive volunteers provided fasting blood samples and underwent neuropsychologic evaluation. Subjects were also evaluated for waist circumference, body mass index (BMI), diabetes, and a number of metabolic variables.

To determine the incidence of NCI, the researchers used a battery of neuropsychologic tests, including global impairment ratings and global deficit scores.

They conducted univariate and multivariate analyses of demographics, biomarkers of HIV, plasma lipids, leptin levels, homeostasis model assessment (a measure of insulin resistance), waist circumference, antiretroviral therapy history, other drug exposure, and self-reported diabetes.

The team then examined BMI as a correlate of NCI in 90 subjects, and BMI and leptin levels as correlates of NCI in 55 subjects.

Dr. McCutchan reported that 40% of 130 participants had some level of NCI.

Univariate models showed associations between NCI and age, longer duration of HIV infection, self-reported diabetes, and waist circumference. Multivariate logistic regression analyses revealed risk factors such as diagnosis of AIDS (odds ratio [OR], 50; P = .02), diagnosis of diabetes (OR, 18; P = .07), and waist circumference (OR, 1.34 per cm; P = .001). Greater body mass had a protective effect (OR, 0.69 per BMI point; P = .04).

BMI is a measure of central fat, which is bad for the brain, Dr. McCutchan noted. Because fat in other areas might be protective, BMI is only protective if waist circumference is incorporated into the model.

"When we control for the adverse effects of central fat, the effects of greater amounts in the remaining body tissue is positive for the brain. We speculate that this remainder is preserved in the less 'frail' patients, who have better brain health," he said.

AIDS-related dementia was common before effective treatment became available, but low-level complaints remain common. "People say: 'I can't get the work done that I used to.' That level of complaint is there in somewhere between 30% and 50% of the [HIV-positive] folks out there," said Dr. McCutchan.

The study was designed to weed out other potential causes of NCI, such as life experience and previous drug treatment. "This is a population that had sort of a tough life. But we're still finding high rates" of NCI after controlling for these factors, Dr. McCutchan explained.

Some newer protease inhibitors appear to have fewer effects on metabolism. "We already have people [wanting to] use them for the prevention of cardiovascular disease, and people don't want to have fat bellies. Those 2 reasons are good enough, but if you add that [other drugs] might damage your brain, it might push patients in that direction," said Dr. McCutcheon.

"It's becoming more and more apparent that measures like these are critically important. I suspect part of the message is to be as heart healthy as you possibly can, get your body mass into a healthy range, and get the fat out of your stomach area. Your brain and cognitive functions are going to appreciate it," James Becker, PhD, professor of psychiatry, neurology, and psychology at the University of Pittsburgh, Pennsylvania, who moderated the session, told Medscape Medical News.

Dr. McCutchan and Dr. Becker have disclosed no relevant financial relationships.

19th Conference on Retroviruses and Opportunistic Infections (CROI): Abstract 490. Presented March 8, 2012.

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