New research suggests that specific oral bacteria may be linked to cognitive function and genetic risk for Alzheimer’s disease in older adults—even before dementia develops.
The findings point to the oral microbiome as a possible factor in brain health, particularly among patients with mild cognitive impairment (MCI).
The study involved 60 healthy adult participants and 55 with MCI who were aged 50 and older. Led by Joanna E L’Heureux of the University of Exeter Medical School in the United Kingdom, the investigators also examined a subgroup of 33 participants with MCI who had known apolipoprotein E (APOE) genotypes. The APOE4 variant is a well-established genetic risk factor for Alzheimer’s disease.
Participants with MCI who had higher levels of Neisseria and Haemophilus bacteria performed better on cognitive tests that assessed executive function, visual attention, and working memory. These bacteria were also associated with higher oral nitrite levels, which is an indicator of nitric oxide (NO) availability. NO plays a vital role in brain function, including blood flow regulation and neural signaling.
In contrast, higher levels of Prevotella intermedia—a bacterium associated with gum disease—were more common in APOE4 carriers. Among noncarriers, P. intermedia levels were inversely related to nitrate and nitrite levels in the mouth. Porphyromonas, another pathogen linked to periodontitis, was found in greater abundance in MCI participants than in healthy controls.
Investigators grouped oral bacteria into modules based on co-occurrence patterns. A module dominated by Neisseria and Haemophilus consistently correlated with better cognitive scores and higher nitrite levels. In contrast, a Prevotella-dominated module was linked to lower NO availability and poorer cognitive performance. These patterns suggest that some bacteria may promote nitric oxide metabolism while others may impair it—potentially influencing brain health.
Despite these associations, overall oral nitrate and nitrite concentrations did not significantly differ between the healthy and MCI groups. Similarly, global measures of microbial diversity—such as species richness and evenness—showed no meaningful differences. Therefore, specific bacteria, rather than overall microbial diversity, were more relevant to cognitive outcomes.
The study had some limitations. Dietary intake, which can affect both nitrate levels and oral microbiota, was not controlled. Most participants were women, which may limit generalizability. In addition, the sequencing method did not confirm the presence of nitrate-reducing genes in the bacteria identified. It only confirmed their taxonomy.
Nevertheless, the study offers new insight into how the oral microbiome might relate to early cognitive changes. The presence and abundance of certain bacteria may reflect or contribute to how the body regulates nitric oxide—a process that declines with age and is disrupted in Alzheimer’s disease.
These findings may inform future research into whether modifying the oral microbiome through diet or oral health interventions could support cognitive function. Further studies using more precise genetic sequencing and dietary monitoring will be needed to clarify the role of oral bacteria in the early stages of cognitive decline.
Full disclosures can be found in the published study.
Source: PNAS Nexus
