Introduction: Increases in brain β-amyloid protein (Aβ) levels have been demonstrated in animal models following oral inoculation of periodontopathogens or their enzyme gingipain. We investigated the association between periodontitis and brain Aβ protein levels in mild cognitive impairment (MCI). Methods: An observational study was designed. All participants underwent a periodontal examination and an amyloid-PET scan. Subsequently, the following groups were established: MCI and suspected Alzheimer disease (AD) (MCI/Aβ+ group) (n = 45); MCI and suspected non-AD pathology (MCI/Aβ– group) (n = 59); cognitively healthy elderly individuals with negative PET-amyloid scan results (non-MCI/Aβ– group) (n = 60). Results: Patients with moderate-severe periodontitis had a higher risk of abnormal accumulation of Aβ in the brain, with an odds ratio (OR) of 3.30 (95% confidence interval [CI], 1.30–8.26) when comparing patients from the MCI/Aβ+ and MCI/Aβ– groups, and an OR of 4.94 (95% CI, 1.65–14.84) when comparing the MCI/Aβ+ group against the non-MCI/Aβ– group. Conclusions: Our findings suggest that periodontal disease may be associated with anomalous accumulation of cerebral Aβ protein in older people, independently of cognitive impairment.