The contribution of oral infectious diseases in lacunar stroke based on meta-analysis and Mendelian randomization study

Introduction

Nowadays, the prevalence of aging and neurodegenerative diseases is on the rise. The 2015 World Population Ageing Report forecasted that the global population aged 60 years and older is expected to more than double over the next 35 years, reaching nearly 2.1 billion individuals¹. This projection underscored the increasing prevalence of population ageing. Stroke, the second most common cause of death globally, occurs in approximately three-quarters of people aged ≥ 65 years. As a result of population ageing, the risk of stroke is expected to rise substantially within 20 years, especially in developing countries^2,3. Lacunar stroke (LS), classified as a subtype of cerebral small vessel disease (CSVD), represents approximately 25% of all ischemic strokes^2,4. LS is linked to cognitive decline and aging, and it exists in the early stage of them^5,6. Therefore, the prevention of LS is crucial. Although the etiology of LS has not yet been adequately identified, inflammation and endothelial dysfunction are acknowledged as potential contributing factors⁷.

Dental caries, pulp and periapical diseases, and periodontitis are significant contributors to oral inflammation. These conditions generate inflammatory mediators that may enter the systemic circulation, potentially affecting distant organs^{8, 9, 10–11}. Several studies supported the effect of periodontitis, as well as pulp and periapical diseases, on the dysfunction of endothelial cells^{12, 13, 14–15}. Therefore, oral infectious diseases can be considered a source of systemic inflammation and endothelial vascular stress. However, the association between oral infectious diseases and LS remains ambiguous. If the interaction between oral infectious diseases and LS is substantiated and reliable, then the proactive management of oral infectious diseases may enhance cerebrovascular health and facilitate the early detection of cerebrovascular disease¹⁶.

Clinical studies have explored the relationship between periodontitis and LS^16,17. The extraction of all available trial data can provide a more accurate evaluation of the relationship between oral infectious diseases and LS. Therefore, this study conducted a meta-analysis of the evidence on the association between oral infectious diseases and LS following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines¹⁸.

However, clinical studies are susceptible to various biases, confounding factors, and reverse causation, which can result in misleading associations. Despite meticulous research...