Is Brain Inflammation At The Core Of Cognitive Decline? What Latest Research Says

Written by Maria Cohut, Ph.D.— Fact checked by Jill Seladi-Schulman, Ph.D.

While the causes behind cognitive decline and, more importantly, dementia, remain uncertain, researchers have taken huge leaps toward identifying likely contributing factors.

One of these key factors appears to be inflammation and, in particular, neuroinflammation, or brain inflammation, which has been linked with cognitive impairment and the development of dementia.

Over the past few months, studies have suggested that one specific virus — the virus that causes cold sores — might trigger Alzheimer’s, but also that common medical treatments like vaccination, antibiotics, and nonsteroidal anti-inflammatory drugs (NSAIDs) are linked to a lower risk of this disease.

“In our study, we detected HSV-1-related proteins in postmortem human brain samples,” Or Shemesh, PhD, assistant professor in the Department of Ophthalmology at The University of Pittsburgh and senior author of this study, told Medical News Today.

This suggests a possible link between the herpes virus and cognitive decline, which previous studies have also found.

Furthermore, research published in the journal mBio in February 2025, which used animal models, identified the potential route through which HSV-1 can penetrate the brain and lead to cognitive impairment.

In this study, mice became infected with this virus through nose exposure. Once in the brain, the herpes virus caused persistent cognitive problems and anxiety in the mice.

Deepak Shukla, PhD, is the study’s lead author, the Marion H. Schenk Esq. Professor in Ophthalmology for Research of the Aging Eye, and professor of microbiology and immunology at the University of Illinois College of Medicine.

In a press release, Shukla explained how this might work in humans:

“If an infected individual is shedding virus via tears, it could reach the nasal cavity, where it could go more directly to the brain. I think [this infection is] underdiagnosed and understudied, but the neurological consequences, we believe, are much more severe than you would normally see with fever blisters or ocular infection.”

The review found that antimicrobial medication, vaccines, and NSAIDs were linked to reduced dementia risk.

Ben Underwood, MA, PhD, FRCPsych, from the Department of Psychiatry at the University of Cambridge and the Cambridgeshire and Peterborough NHS Foundation Trust in the United Kingdom, who was one of the review authors, stressed in a press release that “we urgently need new treatments to slow the progress of dementia, if not to prevent it.”

According to Underwood:

“If we can find drugs that are already licensed for other conditions, then we can get them into trials and — crucially — may be able to make them available to patients much, much faster than we could do for an entirely new drug.”

At the same time, review co-author Ilianna Lourida, PhD, from the National Institute for Health and Care Research Applied Research Collaboration South West Peninsula (PenARC) at the University of Exeter, U.K., cautioned that people should not alter their medication use based on these findings without first consulting a physician.

“It’s important to remember that all drugs have benefits and risks. You should never change your medicine without discussing this first with your doctor, and you should speak to them if you have any concerns,” she advised in her press release statement.

The research, which analyzed data collected from 11,745 participants, found that the use of NSAIDs — such as ibuprofen and aspirin — for a period of over 2 years was associated with a reduced dementia risk.

However, NSAID use did not appear to lower the risk for cognitive decline in people who had a genetic predisposition for dementia.

Some anti-inflammatory drugs, like ibuprofen, can help lower levels of beta-amyloid in the brain. Since the overaccumulation of this protein is associated with dementia, this may explain, in part, the protective effect that some NSAIDs appear to have in the long term.

However, the study noted that NSAIDs like aspirin, which do not have beta-amyloid-lowering properties, were actually associated with a greater decrease in dementia risk.

Vernon Williams, MD, a sports neurologist and founding director of the Center for Sports Neurology and Pain Medicine at Cedars-Sinai Orthopaedics in Los Angeles, who was not involved in this research, told MNT that:

“The findings that the association was stronger for non-amyloid-lowering NSAIDs compared to those with known amyloid-lowering properties is interesting in that it implies the mechanism of action may not be entirely related to amyloid reduction. So other anti-inflammatory pathways and/or genetic risk factor effects may be contributing to the benefits.”

However, like other experts, Williams also cautioned that people should not alter their medication regimen without medical supervision, as “there are potential side effects and risks associated with currently available NSAIDs.”