Edentulism, blood-based neurodegenerative biomarkers, and 10-year dementia risk: A mediation analysis in a nationally representative United States cohort

INTRODUCTION: Tooth loss is associated with dementia risk, but mechanisms remain unclear. We examined whether blood-based neurodegenerative biomarkers mediate the edentulism-cognition association. METHODS: Among 4238 Health and Retirement Study participants aged 50+, we linked edentulism (2012), biomarkers (neurofilament light chain [NfL], glial fibrillary acidic protein [GFAP], phosphorylated tau-181, and amyloid-β [Aβ] 42/40; 2016), and 10-year cognitive outcomes (2012-2022). RESULTS: Edentulism was associated with higher NfL (β = 4.21) and GFAP (β = 8.06), but not pTau-181 or Aβ42/40, and predicted cognitive impairment (hazard ratio [HR] 1.49) and dementia (HR 1.28). GFAP mediated 9.8% and 12.0% of the cognitive impairment and dementia associations, respectively; NfL mediated 9.8% of the dementia association but not cognitive impairment. CONCLUSION: In this observational cohort, elevated NfL and GFAP were associated with, and accounted for a small proportion of, the edentulism-cognition association. These associative findings support further study of oral health in dementia prevention but do not establish a causal effect.