by Wroclaw Medical University

Credit: Wroclaw Medical University

Alzheimer's disease is most commonly associated with memory impairment, disorientation, and irreversible neurodegenerative changes in the brain. We rarely think of it in the context of… a toothbrush. Meanwhile, an increasing number of studies suggest that oral inflammatory processes may be far more important for overall health, especially brain health, than previously assumed. A new study conducted by a team of researchers from the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences (IITD PAN) in Wroclaw, Wroclaw Medical University (UMW), and the University of Connecticut, U.S. (UConn), shows that periodontal tissue status, peripheral immune response, and cognitive functions are closely interconnected.

This is another contribution to the growing discussion on themouth–brain axis, analogous to the well-known gut–brain axis.

From gingivitis to neurodegeneration

Periodontal inflammatory diseases are among the most common oral health problems worldwide. The mildest form—gingivitis—affects up to 90% of the adult population and is often underestimated. However, if inflammation persists, it may become chronic and lead to periodontitis, a bacterial inflammatory disease that causes permanent damage to the tissues supporting the teeth and ultimately results in tooth loss.

Periodontal inflammatory diseases have long been associated with numerous systemic conditions such as cardiovascular diseases, diabetes, and lung diseases. Increasing scientific evidence, however, indicates that they may also affect brain function and the course of Alzheimer's disease.

What did the researchers investigate?

The study,publishedin 2025 in theInternational Journal of Molecular Sciences, included 68 participants: 36 patients with Alzheimer's disease at varying stages of disease progression and 32 cognitively healthy individuals from the same age group. The researchers assessed:

It is this last element that makes the study unique—it not only describes correlations between the two diseases but also demonstrates functional dysregulation of the peripheral immune response.

The immune paradox in Alzheimer's disease

In patients with Alzheimer's disease, researchers observed changes in the profile of peripheral immune cells. The most important finding was that both the overall white blood cell count and specific leukocyte subpopulations (lymphocytes, monocytes), as well as platelets, were significantly reduced compared with cognitively healthy individuals. A reducedSII marker(systemic immune-inflammation index) was also observed. These findings were considered a possible cause of the weakened immune response to bacterial antigens, indicating potential immunological deficiencies in this group of patients.

"In patients with Alzheimer's disease, we do not observe excessive systemic inflammation, but rather certain deficits resulting from immune system weakening and exhaustion," emphasizes Dr. Jacek Zborowski from the Department of Periodontology and Oral Pathology at Wroclaw Medical University, a co-author of the study.

A key discovery was that, under unstimulated conditions, peripheral immune cells from patients with Alzheimer's disease produced significantly fewer pro- and anti-inflammatory cytokines than those from healthy individuals. However, after contact with a bacterial antigen, the immune response was stronger than in healthy controls.

"This is a picture of immune system dysregulation: low baseline activity (exhaustion) combined with hyperreactivity after stimulation. The immune system responds unevenly, in a potentially harmful way,"adds the researcher.

It should be emphasized, however, that this is a more complex process in which elements of chronic inflammation and functional changes in peripheral immune cells coexist and may play different roles in the pathogenesis of Alzheimer's disease, stresses the project leader, Dr. hab. Marta Sochocka from the Department of Immunology of Infectious Diseases and the Virology Laboratory at IITD PAN.

Gums, oral hygiene status, and memory

The most clinically interesting result concerns the relationship between periodontal tissue status and cognitive function. With the increasing severity of Alzheimer's disease, the following indicators increased:

Moreover, the researchers demonstrated that the greater thegingival inflammation(BOP), the lower the MMSE score, regardless of age or sex.

"This is not about advanced periodontitis. Our data suggest that even mild, chronic gingival inflammation may have systemic significance," notes Dr. Zborowski.

The mechanism linking oral bacterial infection and inflammation to the brain

The study suggests the following scenario:

The publication also highlights a very practical issue: people with Alzheimer's disease take significantly less care of their oral hygiene. They brush their teeth less often, twice a day, and almost never use dental floss.

This means that dental prevention cannot rely solely on patient education. It must include caregivers and be part of systemic care.

"The state of oral hygiene in a patient with cognitive impairment is not an 'add-on." It is a systemic parameter that may matter for the course of the disease."emphasizes Dr. Zborowski.

A toothbrush as a tool for Alzheimer's disease prevention

The authors do not announce a new therapy for Alzheimer's disease, but their data clearly suggest that:

At a time when effective causal therapies are still lacking, priority should be given to implementing diagnostics of periodontal inflammation in individuals with cognitive impairment and dementia, especially of the Alzheimer's type. Interventions such as regular oral hygiene may have unexpectedly significant importance in avoiding future consequences for mental health.

Publication details Michał Ochnik et al, Oral and Periodontal Health Status, Peripheral Immune Dysregulation, and Cognitive Impairment in Alzheimer's Disease: A Clinical and Immunological Study, International Journal of Molecular Sciences (2025). DOI: 10.3390/ijms262311752 Journal information: International Journal of Molecular Sciences