Dementia is becoming an increasingly important public health challenge as populations age. And with no cure for most forms of the disease, researchers are looking more closely at factors that may help reduce risk even before symptoms appear.
A new study led by NYU Shanghai Provost and Distinguished Global Professor of Public Health Bei Wu offers new clues about one factor that has repeatedly been associated with cognitive decline later in life: tooth loss.
The study, recently published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, found that people who had lost all of their natural teeth had higher levels of two blood proteins associated with brain injury and inflammatory response. Further analysis suggests that these biological changes may account for part of the statistical link between complete tooth loss, known as edentulism, and later cognitive impairment and dementia.
“We already knew that tooth loss and cognitive decline travel together,” Professor Wu said. “What we did not know was what happens biologically in between.” She and her collaborators have spent years examining oral health and cognitive aging from different perspectives, including tooth loss, genetic risk, diabetes, and social mobility. While previous studies helped establish the association, their new research focuses on how to explain it.
The team analyzed data from 4,238 adults aged 50 and older in the Health and Retirement Study, a nationally representative longitudinal study in the United States. Participants reported whether they had lost all of their natural teeth, provided blood samples, and underwent regular cognitive assessments over a ten-year period.
The blood samples were tested for four neurodegenerative biomarkers that provide different clues about brain health: neurofilament light (NfL), glial fibrillary acidic protein (GFAP), phosphorylated-tau 181 (pTau-181), and the amyloid-beta 42 to 40 ratio (Aβ42/40). Looking at all four together allowed the team to distinguish between different kinds of changes in the brain.
After accounting for demographic, socioeconomic, behavioral, health, dental care, and genetic factors, the research team found that complete tooth loss was associated with higher levels of NfL and GFAP, two biomarkers related to neural injury and immunity. No comparable association was seen with the other two biomarkers, pTau-181 and Aβ42/40, which are more closely tied to classic protein changes seen in Alzheimer’s disease.
“The pattern we found points to general brain inflammation and neuronal injury,” said Xiang Qi, assistant professor at NYU Rory Meyers College of Nursing and lead author of the study. “Edentulism appears to leave a different kind of fingerprint in the blood than Alzheimer’s disease does.”
The study also reinforced the broader relationship between tooth loss and cognitive impairment seen in previous research. Over the ten-year period covered by the study, complete tooth loss was associated with a 49 percent higher risk of cognitive impairment and a 28 percent higher risk of dementia after the researchers adjusted for other relevant factors.
The team then examined how much of that relationship could be statistically accounted for by the blood-based neurodegenerative biomarkers. In the dementia analysis, the GFAP biomarker accounted for only about 12 percent of the association, meaning that most of the relationship remained unexplained by this measured pathway.
“This is an observational study,” Wu said. “What would go beyond the evidence is any claim that losing your teeth causes dementia, or that keeping your teeth prevents it.” The team hopes that future studies with repeated biomarker measurements and more detailed oral health data can further clarify how the relationship between tooth loss and cognitive decline develops over time, and eventually test whether improving oral health can alter biological changes associated with cognitive decline.
The findings add to the team’s broader research on how oral health may be connected to brain health and cognitive aging. “The mouth has been treated as separate from the rest of medicine for a very long time,” Wu said. “The biology does not respect that separation.”