At Northwestern University Feinberg School of Medicine in Chicago, researchers have identified an unexpected culprit behind cognitive decline in people with HIV: the degradation of protective sugar molecules in the body that normally keep inflammation at bay. The discovery opens a surprising therapeutic avenue—flu drugs might slow memory loss and premature aging in people living with chronic viral infection, pointing toward treatments that could eventually address aging-related cognitive problems in the broader population.
At least a quarter of people living with HIV develop memory and thinking problems, even when their viral load is controlled by effective antiretroviral treatment. For decades, the biological mechanisms behind these cognitive symptoms remained mysterious. But a new study, led by Mohamed Abdel-Mohsen at Northwestern and published in Med, reveals a previously overlooked mechanism: the breakdown of glycans, sugar molecules that act as a brake on harmful inflammation. When these protective molecules degrade, chronic inflammation takes hold, accelerating biological aging and driving the immune system into prolonged overdrive.
The research team analyzed blood samples from more than 100 individuals with HIV—some with normal cognition, others with cognitive impairment—and found a clear link between sugar molecule degradation and cognitive decline. They then tested whether flu drugs could reverse the damage. Using immune cells from people with HIV and mouse models, the scientists demonstrated that sialidase inhibitors—a class of flu medications including Tamiflu (oseltamivir)—could preserve those protective sugar molecules and reduce inflammation in the brain. In mice, the treatment slowed biological aging and protected memory function.
The findings carry broader implications. These sialidase inhibitors work by blocking enzymes that degrade glycans, a different mechanism than their conventional use fighting influenza. "We are not saying yet that people should take flu drugs to prevent cognitive decline," cautioned Abdel-Mohsen, an associate professor of medicine in the division of infectious diseases. "We are saying that our findings open the door to testing whether this drug class, or better next-generation versions, could be repurposed for brain and aging-related complications."
The study revealed an intriguing gender difference. Sugar degradation was more pronounced in women, with a striking pattern linked to menopause. In men, these changes occur gradually and steadily with age. But in women, the process starts slowly before menopause, then accelerates sharply around that transition. As Abdel-Mohsen explained, "Before menopause, women show a slower loss of anti-inflammatory glycans and slower accumulation of pro-inflammatory glycans compared with men, but around menopause there is a rapid shift toward a more inflammatory glycan profile."
This discovery could reshape how researchers think about cognitive decline in people with HIV and beyond. Rather than viewing the problem as inevitable, the research suggests that targeting the underlying inflammatory mechanism—through glycan preservation—might offer a new therapeutic strategy. While next-generation versions of these drugs would likely be safer and more effective than current flu medications, the pathway from mouse studies to human treatment remains years away. Still, for the millions of people living with HIV who worry about cognitive changes, and for those watching aging accelerate the brain's decline, the research offers something rare: a biological mechanism and a potential intervention to slow it down.