# Oral Health and Cognitive Decline: A Systematic Review of the Periodontitis-Alzheimer's Connection
## 1 Introduction  
Alzheimer's disease (AD), a progressive neurodegenerative disorder affecting over 55 million people worldwide, represents one of the most pressing global health challenges due to its rising prevalence (projected to reach 139 million by 2050) and socioeconomic impact (costs exceeding $1.3 trillion annually). Periodontal disease (PD), a chronic inflammatory condition affecting >47% of adults globally (with severe forms in 11%), has emergedas a modifiable risk factor for AD, compounding the disease burden through shared pathways of systemic inflammation and microbial dysbiosis [1; 2; 3; 4; 5; 6]. Characterized by cognitive decline, memory impairment, and behavioral changes, Alzheimer's disease is the most common form of dementia, accounting for 60-80% of all cases. Despite extensive research, the etiology and pathophysiology of AD remain incompletely understood, with a complex interplay of genetic, environmental, and lifestyle factors contributing to its onset and progression. Recent evidence has increasingly suggested a link between systemic inflammation and neurodegenerative diseases, with periodontal disease (PD) emerging as a potential modifiable risk factor for AD [7; 8; 9; 10; 11; 12; 13; 14; 15; 16]. Periodontal disease, a chronic inflammatory condition affecting the supporting structures of the teeth, including the gingiva, periodontal ligament, and alveolar bone, is primarily caused by microbial dysbiosis within the oral cavity [17; 18; 19; 20; 21; 22; 23; 24; 25; 26]. It is one of the most prevalent chronic diseases worldwide, affecting up to 50% of adults and increasing in severity with age. The clinical manifestations of PD range from gingivitis, characterized by reversible inflammation of the gingiva, to periodontitis, a destructive and irreversible condition that can lead to tooth loss. Notably, periodontitis is associated with a systemic inflammatory burden and has been linked to various systemic conditions, including cardiovascular disease, diabetes mellitus, and rheumatoid arthritis [27; 28; 29; 30; 31; 32; 33; 34; 35; 36]. In recent years, the potential connection between periodontal disease and Alzheimer's disease has garnered significant attention [37; 38; 39; 40; 41; 42; 43; 44; 45; 46]. The proposed link is grounded in the hypothesis that chronic systemic inflammation, driven by periodontal pathogens and their virulence factors, may contribute to neuroinflammation and the pathological processes underlying AD [47; 48; 49; 50]. This bidirectional relationship suggests that while periodontal disease may act as a risk factor for Alzheimer's, the cognitive decline associated with AD may also exacerbate oral health issues, creating a vicious cycle [51; 52; 53; 54; 55; 56; 57; 58; 59]. This introduction aims to provide a comprehensive overview of the potential mechanisms linking periodontal disease to Alzheimer's disease, explore the epidemiological evidence supporting this association, and discuss the implications for early diagnosis, prevention, and treatment. The emerging paradigm underscores the importance of interdisciplinary collaboration between dentistry, neurology, and other healthcare fields to address the shared inflammatory pathways and systemic implications of these conditions [60; 61; 62; 63; 64; 65; 66; 67; 68; 69].