Oral Microbiome Associated with Cognitive Performance

An analysis of oral microbes in older adults has indicated an association between microbial diversity and executive function performance [1].

Multiple factors impact cognitive impairment risk

Aging is one of the major risk factors for cognitive impairment and dementia, but it is not the only one. According to multiple research papers, the risk of developing cognitive impairment and dementia is impacted by factors such as lower educational level; toxin exposure; physical inactivity; systemic inflammation; comorbidities such as diabetes, cardiovascular disease, and stroke; and gut dysbiosis: the perturbed composition of gut microbes [2, 3, 4, 5].

While the gut microbiome is well studied, microbes in the oral cavity get less attention. However, some studies suggest a connection between oral cavity dysbiosis and neurodegenerative disorders. This prompted the researchers to test the association between the oral microbiome and Alzheimer’s disease in small-scale clinical studies. The results of those studies do not give a clear answer, since some of the studies report a connection while others don’t see it [6, 7].

In this study, the researchers aimed to build on that knowledge and address a similar question: whether “the oral microbiome is associated with cognitive function measurements” in older adults.

They used data from the National Health and Nutrition Examination Survey (NHANES) 2011-2012, a study conducted by the U.S. Centers for Disease Control and Prevention (CDC). For their analysis, the authors used data from 605 adults between 60 and 69 years old.

Microbes and cognitive function

During the initial analysis, the researchers observed significantly lower scores for all the cognitive tests performed in the older participants with lower educational levels, lower income, current smoking, lower physical activity, and pre-existing diabetes and hypertension.

More in-depth analysis looked at microbiome α- and β-diversity. α-diversity indicates microbiome diversity within a given sample, and β-diversity compares diversity between samples. The analysis revealed a significant positive association between α-diversity and the Digit Symbol Substitution Test (DSST), which measures brain health based on executive function and processing speed. The author’s models pointed out that “higher α-diversity was significantly associated with higher odds of better cognitive function based on DSST.” The results also suggested the importance of β-diversity for DSST.

However, other cognitive domains didn’t show significant associations with α- and β-diversity. Taken together, these resultst suggest that oral dysbiosis has an impact on executive function as tested with DSST, but there was no significant impact on verbal memory as tested with other cognitive tests.

The models also identified the association between the oral microbiome and subjective memory changes. Specifically, higher levels of α-diversity in participants were associated with a lower possibility of experiencing subjective memory changes, and participants who experienced subjective memory changes had significantly different β-diversity than those who didn’t experience them.

The authors discuss that their results are mostly consistent with similar observations by other researchers. If differences arise, they can be caused by different methods of obtaining samples or small cohorts in some studies that were insufficient for proper statistical analysis.

Potential role of inflammation

The authors elaborate on the potential mechanisms underlying the connection between oral microbial dysbiosis and cognitive function impairment. Based on previous research, they hypothesize the role of inflammation in this process, as, for example, other researchers found higher concentrations of inflammatory markers in plasma or cerebrospinal fluid in patients with mild cognitive impairment compared to normal individuals [8].

They also suggest that changes to the oral microbiome can be a potential source of low-grade systemic inflammation, which might play a role in cognitive impairment and dementia development. They give an example of a periodontal disease associated with oral microbial dysbiosis and increased pro-inflammatory mediators.

Large dataset with some limitations

The large dataset used in this study was one of its major strengths compared to smaller studies. Additionally, the availability of other information describing this cohort allowed for adjustment for extensive covariates. However, like every study, this one suffers from some limitations, including the inability to infer causality, which means that the results of this study cannot tell “whether cognitive impairment occurred before or after oral dysbiosis or whether declining health itself influenced both cognitive function and the oral microbial community.”

Since the data of specific microbial species is unavailable in NHANES, that limites the analysis. The generalizability of the results is also limited to this study’s particular age group. The authors also mention that their choice of statistical analysis (not correcting for a number of comparisons) increases the risk of false positives.

In this cross-sectional analysis using data from the NHANES 2011–2012, we found that the α-diversity of the oral microbiome was significantly associated with DSST among U.S. older adults aged 60–69 years after controlling for potential confounding variables. Moreover, cognitive function status based on DSST was associated with distinct oral microbial compositions. Similar results were also identified in the association between the oral microbiome and subjective memory changes. Our study highlights the potential contribution of the oral microbiome to the maintenance of normal cognitive function.

Literature

[1] Lin, T. Y., Wang, P. Y., Lin, C. Y., & Hung, S. C. (2024). Association of the oral microbiome with cognitive function among older adults: NHANES 2011-2012. The journal of nutrition, health & aging, 28(8), 100264. Advance online publication.

[2] Livingston, G., Huntley, J., Sommerlad, A., Ames, D., Ballard, C., Banerjee, S., Brayne, C., Burns, A., Cohen-Mansfield, J., Cooper, C., Costafreda, S. G., Dias, A., Fox, N., Gitlin, L. N., Howard, R., Kales, H. C., Kivimäki, M., Larson, E. B., Ogunniyi, A., Orgeta, V., … Mukadam, N. (2020). Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet (London, England), 396(10248), 413–446.

[3] Kipinoinen, T., Toppala, S., Rinne, J. O., Viitanen, M. H., Jula, A. M., & Ekblad, L. L. (2022). Association of Midlife Inflammatory Markers With Cognitive Performance at 10-Year Follow-up. Neurology, 99(20), e2294–e2302.

[4] Seo, D. O., & Holtzman, D. M. (2020). Gut Microbiota: From the Forgotten Organ to a Potential Key Player in the Pathology of Alzheimer’s Disease. The journals of gerontology. Series A, Biological sciences and medical sciences, 75(7), 1232–1241.

[5] Meyer, K., Lulla, A., Debroy, K., Shikany, J. M., Yaffe, K., Meirelles, O., & Launer, L. J. (2022). Association of the Gut Microbiota With Cognitive Function in Midlife. JAMA network open, 5(2), e2143941.

[6] Wu, Y. F., Lee, W. F., Salamanca, E., Yao, W. L., Su, J. N., Wang, S. Y., Hu, C. J., & Chang, W. J. (2021). Oral Microbiota Changes in Elderly Patients, an Indicator of Alzheimer’s Disease. International journal of environmental research and public health, 18(8), 4211.

[7] Cirstea, M. S., Kliger, D., MacLellan, A. D., Yu, A. C., Langlois, J., Fan, M., Boroomand, S., Kharazyan, F., Hsiung, R. G. Y., MacVicar, B. A., Chertkow, H., Whitehead, V., Brett Finlay, B., & Appel-Cresswell, S. (2022). The Oral and Fecal Microbiota in a Canadian Cohort of Alzheimer’s Disease. Journal of Alzheimer’s disease : JAD, 87(1), 247–258.

[8] Shen, X. N., Niu, L. D., Wang, Y. J., Cao, X. P., Liu, Q., Tan, L., Zhang, C., & Yu, J. T. (2019). Inflammatory markers in Alzheimer’s disease and mild cognitive impairment: a meta-analysis and systematic review of 170 studies. Journal of neurology, neurosurgery, and psychiatry, 90(5), 590–598.