Increased Odds of Incident Alzheimer’s Disease and Related Dementias in Presence of Common Non-Cancer Chronic Pain Conditions in Appalachian Older Adults

There is a growing concern regarding the increasing prevalence of common non-cancer chronic pain conditions (NCPCs) and their possible association with Alzheimer's disease and related dementias (ADRD). However, large population-based studies are limited, especially in Appalachian and other predominantly rural, underserved populations who suffer elevated prevalence of both NCPCs and known ADRD risk factors.We investigated the relation of NCPC to risk of incident ADRD in older Appalachian Medicare beneficiaries and explored the potential mediating effects of mood and sleep disorders.Using a retrospective cohort design, we assessed the overall and cumulative association of common diagnosed NCPCs at baseline to incident ADRD in 161,573 elders ≥65 years, Medicare fee-for-service enrollees, 2013-2015. NCPCs and ADRD were ascertained using claims data. Additional competing risk for death analyses accounted for potential survival bias.Presence of any NCPC at baseline was associated with significantly increased odds for incident ADRD after adjustment for covariates [adjusted odds ratio (AOR) = 1.26 (1.20, 1.32), p < .0001]. The magnitude and strength of this association increased significantly with rising burden of NCPCs at baseline [AOR for ≥4 vs. no NCPC = 1.65 (1.34, 2.03), p-trend = .01]. The addition of depression and anxiety, but not sleep disorders, modestly attenuated these associations [AORs for any NCPC and ≥4 NCPCs, respectively = 1.16 (1.10, 1.22) and 1.39 (1.13, 1.71)], suggesting a partial mediating role of mood impairment. Sensitivity analyses, multinomial logistic regressions accounting for risk of death, yielded comparable findings.In this large cohort of older Appalachian Medicare beneficiaries, baseline NCPCs showed a strong, positive, dose-response relationship to odds for incident ADRD; this association appeared partially mediated by depression and anxiety. Further longitudinal research in this and other high-risk, rural populations are needed to evaluate the causal relation between NCPC and ADRD.