Summary: New research identifies a previously unrecognized biological mechanism that contributes to cognitive decline and accelerated aging in people living with chronic viral infections. The team found that breakdown of protective, anti-inflammatory sugar molecules called glycans promotes persistent systemic inflammation in people with HIV.
Using sialidase inhibitors — a drug class commonly used against influenza (for example, oseltamivir/Tamiflu) — researchers were able to preserve these glycan structures in preclinical models. Preserving glycans reduced neuroinflammation, slowed markers of biological aging, and protected memory-related brain circuits.
Key Facts
- The persistent cognitive deficit: Around 25% of people living with HIV experience ongoing problems with memory and thinking despite effective antiretroviral therapy that suppresses the virus.
- Glycan degradation drives inflammation and aging: The study highlights that loss of protective sugar chains on blood proteins fuels chronic inflammation. Ongoing inflammation pushes the immune system into a prolonged activated state that accelerates biological aging.
- Human cohort analysis: Investigators linked this glycan-loss mechanism to cognitive impairment by analyzing blood samples from more than 100 HIV-positive participants enrolled in the AIDS Clinical Trials Group.
- Repurposing sialidase inhibitors: Drugs like oseltamivir typically block a viral enzyme. In these experiments they were used to inhibit host enzymes that remove protective glycans, thereby preserving anti-inflammatory sugar structures.
- Preclinical protection of memory: In cell and mouse models that mimic HIV-associated inflammation, treatment with sialidase inhibitors maintained glycan integrity, lowered inflammatory markers, slowed signs of premature aging, and preserved cognitive performance.
- Sex differences and menopause: Glycan loss followed different timelines in men and women. In men the shift toward a pro-inflammatory glycan profile was gradual with age; in women, the protective glycan profile persisted longer but then shifted rapidly toward inflammation around menopause.
- Path to translation: Lead investigator Dr. Mohamed Abdel-Mohsen emphasizes that although sialidase inhibitors are approved and safe for short-term influenza treatment, additional preclinical work is needed to determine appropriate dosing, duration, and predictive biomarkers before testing these drugs for long-term neuroprotection in people.
Source: Northwestern University
A class of influenza drugs shows promise for reducing cognitive decline and premature aging linked to chronic viral infection, according to a Northwestern-led study that began with blood samples from people with HIV and progressed to preclinical drug trials.
The results point to a potential therapeutic strategy for cognitive impairment in people with HIV and suggest broader relevance for other age-related brain conditions, including forms of dementia tied to chronic inflammation.
The study is scheduled for publication on June 5 in Med, a Cell Press journal.
Despite successful viral suppression with antiretroviral therapy, a significant subset of people living with HIV develop measurable deficits in memory and cognition. The biological drivers of these symptoms have been unclear. In this study, Northwestern researchers pinpointed degradation of protective glycans on blood proteins as a key contributor to chronic inflammation that appears to accelerate biological aging and impair brain function.
The team first analyzed blood samples from over 100 people with HIV who were enrolled in the AIDS Clinical Trials Group and classified by clinical testing as having either normal cognition or cognitive impairment. Patterns of glycan loss correlated with the presence of cognitive difficulties. These human observations guided follow-up laboratory and animal experiments.
In cellular assays and two mouse models of HIV-related inflammation, investigators tested whether preventing glycan removal would lower inflammatory signaling. They treated cells and animals with sialidase inhibitors — including oseltamivir combined with an experimental compound — to block host enzymes that remove the protective sugar coatings on proteins. Treated animals showed preserved glycan profiles, reduced systemic and neuroinflammation, slower accumulation of aging markers, and better performance on memory tests.
“We are not saying people should begin taking flu drugs to prevent cognitive decline,” said study lead author Mohamed Abdel-Mohsen, associate professor of medicine in the division of infectious diseases at Northwestern University Feinberg School of Medicine. “What our findings do is open a path to testing whether this drug class, or improved next-generation inhibitors, can be repurposed for preventing brain and aging-related complications.”
A Northwestern Medicine patient who has lived with HIV for nearly 40 years is available to discuss the importance of ongoing HIV research.
How the study was conducted
First, researchers profiled the glycan patterns on blood proteins from people with HIV who were clinically categorized by cognitive status. That analysis revealed a clear association between glycan degradation and cognitive impairment. Next, they used immune cells from people with HIV and experimental mouse models to test causality: removing glycans increased inflammatory signaling, while blocking the enzymes that remove glycans reduced inflammation. Finally, treatment with sialidase inhibitors in mice preserved glycan structures, decreased inflammatory markers, slowed biological aging indicators, and protected memory performance.
Sialidase inhibitors such as oseltamivir typically act against an influenza enzyme that helps the virus spread. In these experiments, the drugs were repurposed to inhibit human sialidase enzymes that would otherwise degrade protective glycan chains on proteins.
Stronger effects in women
The pattern of glycan loss differed by sex: men tended to show a steady, age-related decline in anti-inflammatory glycans, while women maintained a protective glycan profile longer but experienced a rapid shift toward a pro-inflammatory profile around menopause. Abdel-Mohsen, who is also affiliated with Feinberg’s Potocsnak Longevity Institute, noted that this sex-specific trajectory may help explain why cognitive and inflammatory risks change more abruptly in women during midlife.
Next steps
The research team is pursuing two main directions: refining drug strategies in preclinical models to determine optimal agents, dosing, and treatment duration, and developing blood-based glycan biomarkers that could predict who is at higher risk for future cognitive decline. Abdel-Mohsen stressed that while certain sialidase inhibitors are already approved for short-term influenza use, they have not yet been tested for long-term neuroprotective purposes or for the specific dosing regimens needed in this context.
Key Questions Answered:
A: By targeting different enzymes in the body. Rather than blocking a viral enzyme, the drug class was used to inhibit human enzymes that remove glycans — the sugar molecules that help control inflammation. Preserving glycans keeps inflammation in check and may protect brain health.
A: Menopause appears to mark a rapid decline in protective glycan defenses. Before menopause, women tend to retain more anti-inflammatory glycans; around menopause, these protective sugars decline faster, allowing pro-inflammatory signals to accumulate more quickly than the gradual changes typically seen in men.
A: No. The research is preclinical and exploratory. Although sialidase inhibitors are approved for short-term influenza treatment, they have not been evaluated for long-term use, for this indication, or at the doses and schedules needed to test cognitive benefit. More preclinical optimization and carefully designed clinical trials are required.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal article was reviewed in full by the editorial team.
- Additional contextual reporting was added by staff.
About this neuropharmacology and cognitive decline research news
Author: Ben Schamisso
Source: Northwestern University
Contact: Ben Schamisso – Northwestern University
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Inhibiting glycan degradation prevents HIV-induced inflammaging and cognitive impairment” by Leila B. Giron, Alejandra Borjabad, Eran Hadas, Janeway Granche, Erika G. Marques de Menezes, Thomas A. Premeaux, Hongxia He, Stephen T. Yeung, Shalini Singh, Courtney Friday, Joshua Glover, Eric Balboa, Derrick Dopkin, Michelle Burrows, Anthony Secreto, Nicolas Skuli, Hiroaki Tateno, Paul W. Denton, Frank Palella, Michael J. Corley, Lishomwa C. Ndhlovu, Philip J. Norris, Katherine Tassiopoulos, David J. Volsky, and Mohamed Abdel-Mohsen.
DOI: 10.1016/j.medj.2026.101175
Abstract
Inhibiting glycan degradation prevents HIV-induced inflammaging and cognitive impairment
People with HIV can develop memory and cognitive difficulties even when antiretroviral therapy keeps viral replication under control. Understanding why these impairments occur is important because they affect quality of life and may worsen with aging.
This study found that people with HIV and cognitive symptoms showed greater loss of protective sugar molecules on blood proteins, with the pattern particularly evident in women. In mouse models, drugs that prevented removal of those sugars reduced harmful inflammation, slowed aging-related changes, and prevented memory impairment.
These results suggest protective glycans could serve as biomarkers to identify individuals at higher risk and that preventing glycan degradation offers a potential new approach to treating brain and aging-related complications associated with long-term viral infection.