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Background  Periodontitis and Alzheimer disease (AD) are associated with systemic inflammation. This research studied serum IgG to periodontal microbiota as possible predictors of incident AD.    Methods  Using a case-cohort study design, 219 subjects (110 incident AD cases and 109 controls without incident cognitive impairment at last follow-up), matched on race-ethnicity, were drawn from the Washington Heights-Inwood Columbia Aging Project (WHICAP), a cohort of longitudinally followed northern Manhattan residents aged >65 years. Mean follow-up was five years (SD 2.6). In baseline sera, serum IgG levels were determined for bacteria known to be positively or negatively associated with periodontitis ( Porphyromonas gingivalis ,  Tannerella forsythia, Actinobacillus actinomycetemcomitans  Y4,  Treponema denticola, Campylobacter rectus, Eubacterium nodatum,  and  Actinomyces naeslundii  genospecies-2). In all analyses, we used antibody threshold levels shown to correlate with presence of moderate-severe periodontitis.    Results  Mean age was 72 years (SD 6.9) for controls, and 79 years (SD 4.6) for cases (p<0.001). Non-Hispanic Whites comprised 26%, non-Hispanic Blacks 27%, and Hispanics 48% of the sample. In a model adjusting for baseline age, sex, education, diabetes mellitus, hypertension, smoking, prior history of stroke, and apolipoprotein E genotype, high anti- A. naeslundii  titer (>640 ng/ml, present in 10% of subjects) was associated with increased risk of AD (HR = 2.0, 95%CI: 1.1–3.8). This association was stronger after adjusting for other significant titers (HR = 3.1, 95%CI: 1.5–6.4). In this model, high anti- E. nodatum  IgG (>1755 ng/ml; 19% of subjects) was associated with lower risk of AD (HR = 0.5, 95%CI: 0.2–0.9).    Conclusions  Serum IgG levels to common periodontal microbiota are associated with risk for developing incident AD.

Serum IgG Antibody Levels to Periodontal Microbiota Are Associated with Incident Alzheimer Disease