〔Abstract〕 ObjectiveTo investigate the relationship between periodontitis severity and brain functional indices-amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) in cognitively normal middle-aged and older adults, and to examine their associations with cognitive performance. Methods42 cognitively normal middle-aged and older participants were enrolled. Periodontal data—including the number of remaining teeth (NTP), bleeding on probing positivity rate (BOP%), probing depth (PD), and clinical attachment loss (CAL) as well as resting-state functional magnetic resonance imaging data were collected. Participants were divided into a mild periodontitis group and a moderate-to-severe periodontitis group according to periodontitis severity. Group differences in ALFF and fALFF were compared, and correlation analyses were performed. ResultsCompared with the mild periodontitis group, the moderate-to-severe group showed decreased ALFF values in the right lingual gyrus, superior occipital gyrus, paracentral lobule, and in the left calcarine cortex as well as the precentral and postcentral gyri. Decreased fALFF values were observed in the right lingual gyrus, cuneus, and left calcarine cortex. Indicators related to periodontitis progression [BOP%, PD=4~5mm (%), PD ≥6 mm (%), CAL=3~4 mm (%) and CAL≥5 mm (%)] were negatively correlated with ALFF, fALFF and cognitive performance, whereas indicators reflecting better periodontal function [PD=1~3 mm (%) and CAL=0~2mm (%)] were positively correlated with these measures. ConclusionIn cognitively normal middle-aged and older adults, periodontitis severity is associated with alterations in brain functional activity and cognitive performance.