Periodontitis associated with multi-region brain functional alterations and cognitive impairment: A cross-sectional study in normal cognition,amnestic mild cognitive impairment,and Alzheimer's disease
Restricted accessResearch articleFirst published online April, 2026
Periodontitis associated with multi-region brain functional alterations and cognitive impairment: A cross-sectional study in normal cognition,amnestic mild cognitive impairment,and Alzheimer's disease
Growing evidence links periodontitis to Alzheimer's disease (AD), yet the specific links between periodontitis severity gradients and brain functional alterations remain poorly understood.
Objective
To investigate brain functional alterations quantified by functional connectivity density (FCD) and regional homogeneity (ReHo) across periodontitis severity gradients, include microbiota measures as explanatory variables, and assess correlations between these functional alterations and cognitive impairment.
Methods
Clinical periodontal data, subgingival plaque, cognitive tests, and brain MRI data were collected from all 89 participants, including community-recruited normal cognition (NC) and patients with amnestic mild cognitive impairment (aMCI) and AD from a hospital neurology department. According to periodontal examination, participants were categorized into mild, moderate, and severe groups. FCD and ReHo were compared among different periodontal condition groups and subgroups. Correlation analyses were conducted to explore the relationship among FCD, ReHo, periodontal indices, and cognition.
Results
With increasing severity of periodontitis, the FCD of bilateral middle frontal gyrus (MFG.R, MFG.L), right inferior frontal gyrus, triangular part (IFGtriang.R), and the ReHo of IFGtriang.R all decreased. These regions are commonly associated with executive control, working memory, and attention. These changes were more strongly correlated with overall periodontal inflammatory burden and cognitive performance than to the abundance of specific taxa in the subgingival plaque microbiota.
Conclusions
Periodontitis severity is associated with reduced prefrontal FCD/ReHo and cognitive decline, and these associations appear to be more strongly driven by overall periodontal inflammatory burden than by specific subgingival taxa.
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