Project summary Alzheimer's disease and related dementias (ADRD) is irreversible, progressive brain disease that affects 5.7 million Americans. It is the sixth leading cause of death among all adults and the fifth leading cause of death for those aged 65 or older. ADRD is devastating for individuals and families financially and emotionally. Identifying both individual and combined risk factors of ADRD and evaluating the impact of comorbidities on cognitive impairment is essential to improve cognitive health of older adults. Diabetes and poor oral health are common among older adults and both are risk factors for ADRD. The proposed study is the first to examine the joint effect (additive or interactions) of both DM and poor oral health on ADRD and mortality, and the pathways from the co-occurrence to the onset of ADRD and mortality. Specific aims are: Aim 1a: To examine the relationship between the co-occurrence of DM and poor oral health and the incidence of ADRD using a propensity matched sample within the study period. We hypothesize that persons with both DM and poor oral health will be more likely to have ADRD than those without either condition, or those with only one of these two conditions. Aim 1b: To examine the association between the co-occurrence of DM and poor oral health and the age of first diagnosis of ADRD among persons who developed ADRD during the study period. We hypothesize that persons with both DM and poor oral health will have a younger age of diagnosis of ADRD. Aim 1c: To test the pathways from the co-occurrence of DM and poor oral health to the onset of ADRD by examining the mediation effect of key mediating variables (i.e., CVD and stroke developed after baseline). The relationship between the co-occurrence and the incidence of and the onset of ADRD is mediated by CVD and stroke. Aim 2a: To examine the pathways of the co-occurrence of DM and poor oral health and the effect of key mediators, listed in Aim 1c, on death within 5 years of the study baseline. We will divide the study sample into four groups: alive with ADRD, alive without ADRD, died with ADRD, and died without ADRD. We hypothesize that the co-occurrence has both direct and indirect effects on death. Aim 2b: To use predictive modeling to identify moderators (e.g., childhood adversity, dietary intake, and genetic factors) of the relationship between the co-occurrence of DM and poor oral health and death within 5 years of the baseline survey. The proposed study is the first to examine the effect of the co-occurrence of DM and poor oral health on ADRD and mortality, using large national samples. The proposed study will contribute to a better understanding of the risk profile of ADRD by providing important empirical evidence on the combined risk of both DM and oral health for ADRD. Further, it may identify modifiable factors that can serve as targets to reduce the risk of ADRD. The findings will have important implications for clinical practice and policy initiatives for integrating primary care and dental care.

Project Narrative The proposed study is the first to estimate the joint effect of both diabetes (DM) and poor oral health on Alzheimer's Disease & Related Dementias (ADRD) and mortality, and the pathways from the co-occurrence to ADRD and mortality. This study will contribute to a better understanding of the risk profile of ADRD by providing important empirical evidence on the combined risk of both DM and poor oral health for ADRD. Further, it may identify modifiable factors that can serve as targets to reduce the risk of ADRD.