Oral and Periodontal Health Status, Peripheral Immune Dysregulation, and Cognitive Impairment in Alzheimer’s Disease: A Clinical and Immunological Study

Periodontal disease (PeD), a chronic oral infectious-inflammatory condition, has been linked to systemic inflammatory processes, which may contribute to the onset or progression of various systemic disorders including Alzheimer's disease (AD). We hypothesized that worsening oral and periodontal health, leading to the development of PeD, is associated with cognitive impairment and AD progression as well as peripheral immune system dysregulation. This study included 68 participants: 36 with AD and 32 cognitively healthy, age-matched controls (HCs). Periodontal assessment was performed for diagnosis of PeD (gingivitis or periodontitis). Correlations between oral and periodontal health status, cognitive impairment, and AD severity were evaluated. Peripheral immunity markers were investigated. Peripheral blood leukocytes (PBLs) were stimulated ex vivo with LPS from <i>Porphyromonas gingivalis</i> (LPS-PG) to assess cytokine IFN-γ, TNF-α, IL-1β, IL-6, IL-10, and IL-15 production. The average levels of peripheral immunity markers were significantly lower in AD compared to HCs. AD severity was associated with poorer oral hygiene and increased periodontal tissue inflammation. PBLs from AD patients exhibited a baseline impairment in immune responsiveness reflected in decreased spontaneous TNF-α, IL-1β, IL-6, and IL-10 production. Nevertheless, stronger activation in response to LPS-PG was observed. Poorer oral health status in AD was associated with reduced levels of IL-10 and IL-6. Poor oral and periodontal health may contribute to cognitive impairment and AD progression. Even mild inflammation in periodontal tissue or gingivitis may already influence peripheral immune cell conditions, which in turn might be related to negative consequences for the brain and mental health.