Periodontal disease and cognitive disorders

Periodontitis and tooth loss have been suggested to be putative aetiological risk factors for dementia and cognitive dysfunction. The identification of new dementia risk factors could lead to new preventive strategies for dementia. The aim of this thesis was to explore whether periodontal disease and tooth loss are associated with cognitive dysfunction, with special reference to dementia.

In paper I, 154 cases from the Karolinska Memory Clinic at Karolinska University Hospital and 76 cognitively healthy controls from Huddinge municipality were enrolled in a casecontrol study. Cases comprised individuals diagnosed with Alzheimer´s disease (AD), mild cognitive impairment (MCI), or subjective cognitive decline (SCD). All participants underwent dental examinations that included panoramic imaging. The primary exposure was radiologically verified marginal alveolar bone loss (MABL). Generalised MABL was found to be more prevalent among cases than controls, especially for the AD subgroup. No between-group differences were found for localised MABL. In addition, cases had an overall poorer oral health status than controls.

Paper II explored the subgingival microbiota among AD, MCI and SCD participants and controls from paper I. Using 16S rRNA gene sequencing, the compositions of the microbial communities were compared across study groups. Only relatively subtle differences were seen. As signs of periodontitis were more common among the cases than the controls, it was difficult to determine whether there would have been actual differences had the periodontitis distributions been the same. In periodontitis-adjusted models, we demonstrated that the bacterium Prevotella oulorum was present at a higher abundance among cases than controls and that the bacterium Rothia aeria was less abundant.

In paper III, we investigated the dementia incidence in a cohort with or without periodontal disease at baseline. Data were retrieved from several national registries in Sweden, such as the Swedish Quality Registry for Caries and Periodontal Diseases and the Swedish Dementia Registry. During the average eight years of follow-up, the incidence of dementia was shown to be similar in the two groups. No association was evident between periodontal disease and dementia in confounder-adjusted regression models.

Paper IV was a cohort study using data from Swedish national registries to investigate whether tooth loss is associated with the incidence of dementia. Two exposure groups were defined at the start of the observation period and followed for up to nine years. Severe tooth loss (STL) was contrasted with a reference group without the index condition. The dementia incidence was higher in the group with STL than in the reference group. This finding was found to be robust in sensitivity analyses and the confounder-adjusted models.

In conclusion, the results in this thesis show the complexity of interactions between dental disease and cognitive dysfunction. Among participants with cognitive dysfunction, signs of generalised MABL were more prevalent compared to controls. Differences in the subgingival microbiota were seen, suggesting that cognitive dysfunction was associated with periodontal disease. In a longitudinal study, periodontal disease was not associated with an increased risk of dementia. In contrast, having severe tooth loss was associated with an increased incidence of dementia. Thus, severe tooth loss may serve as a marker of dementia risk.

List of scientific papers

I. Holmer J, Eriksdotter M, Schultzberg M, Pussinen PJ, Buhlin K. Association between periodontitis and risk of Alzheimer′s disease, mild cognitive impairment and subjective cognitive decline: A case-control study. Journal of Clinical Periodontology. 2018;45(11):1287–98.
https://doi.org/10.1111/jcpe.13016

II. Holmer J, Aho V, Eriksdotter M, Paulin L, Pietiäinen M, Auvinen P, Schultzberg M, Pussinen PJ, Buhlin K. Subgingival microbiota in a population with and without cognitive dysfunction. Journal of Oral Microbiology. 2021;13(1).
https://doi.org/10.1080/20002297.2020.1854552

III. Holmer J, Eriksdotter M, Häbel H, Hed Myrberg I, Jonsson A, Pussinen PJ Garcia-Ptacek S, Jansson L, Sandborgh-Englund G, Buhlin K. Periodontal conditions and incident dementia: a nationwide Swedish cohort study. Journal of Periodontology. 2022;1-9.
https://doi.org/10.1002/JPER.21-0518

IV. Holmer J, Eriksdotter M, Häbel H, Jansson L, Pussinen PJ Garcia-Ptacek S, Sandborgh-Englund G, Buhlin K. Severe tooth loss and dementia in a Swedish population-based cohort: a registry-based study. [Manuscript]