Impact of sugar and periodontal disease on cognition: epidemiological and experimental study – DENTALCOG

In aging societies, identifying new ways to preserve cognitive health has become a major concern. In this context, the study of the oral cavity and periodontal disease is of growing interest. Periodontal disease, the most severe form of which is periodontitis, is a dysbiotic chronic inflammatory disease, characterized by the loss of tooth-supporting tissues, leading to tooth loss and which can trigger or worsen systemic disorders. Porphyromas gingivalis, a key bacterial player in periodontitis, often contributes to oral dysbiosis and is also able of colonizing the brain. Its virulence factors (gingipains), which have been found in the brains of Alzheimer's patients, could reinforce amyloid and tau pathologies. Thus, the brain is exposed to immunogenic virulence factors and inflammatory mediators that could be involved in the pathogenesis of Alzheimer's disease (AD).
Recent studies have shown that the excessive consumption of sugars (i.e. refined carbohydrates) in western society is also a common risk factor for periodontal disease and AD. This high consumption leads to hyperglycemia, hyperinsulinemia and leads to insulin resistance. In turn, this insulin resistance is a major risk factor for periodontal disease and AD.
Taken together, these data suggest relationships between sugar consumption, periodontal disease and cognitive processes that have never been evaluated in the general population.
While the oral cavity is a major route of contamination, the impact of periodontal disease on cognition is still largely unknown, as studies in this area have strong methodological limitations (few confounding variables, few cognitive domains studied, inclusion of only older participants, no estimation of the "dose-response" relationship: from gingivitis to periodontitis) The DentalCog project has the resources to overcome these methodological obstacles.
The main objectives of the project are:
i) To analyze in two complementary cohorts in general population (CONSTANCES and 3C) the interrelationships between refined carbohydrate consumption, periodontal disease and cognition, as well as the associated changes in brain and plasma biomarkers.
ii) To validate the epidemiological results and decipher in an animal model (5xFAD mice) the impact of excessive sucrose consumption on periodontitis, oral microbiota and cognition. Such an experimental study is only possible on an animal model (for ethical and temporal reasons) which also avoids confounding factors related to lifestyle.
The prospective cohorts Constances and 3C provide complementary data on exposure variables (periodontal disease, sugar consumption) and biomarkers (MRI & plasma). In the two cohorts, cognitive tests allow us to assess global cognitive functions, memory, executive functioning, attention, verbal fluency, psychomotor speed from the age of 45 years. In 3C an etiologic diagnostic of dementia is available at each follow-up.
Based on the high-level competencies of our consortium who has solid experience in multiple domains (epidemiology, cognition, nutrition, periodontology, neuropharmacology, microbiology and evolutionary biology), the multidisciplinary DentalCog project combines epidemiological and experimental approaches with the aim of offering the opportunity to better understand the impact of sugar and periodontal disease on cognition. This project could also be beneficial in terms of public health and may open the way to new prevention strategies of cognitive decline and dementia.