Outcomes: Periodontitis was associated with poor cognitive performance and progression of cognitive impairment (hazard ratio [HR] = 1.8). The baseline levels of p-Tau (p < 0.001) and amyloid-β (Aβ) 1–40 (p = 0.036) in periodontitis patients were significantly higher than those in non-periodontitis patients. The concentration of Aβ protein increased with time in the periodontitis group (p = 0.005). Conclusions: Periodontitis is associated with cognitive decline. In addition, overexpression of p-Tau and Aβ may play a role in this association. The gene discussed is MAPT; the disease is periodontitis.