Association of Illicit Drug Use and Age at First Use with Alzheimer’s Disease in US Adults: A Cross-Sectional Study from NHANES

BACKGROUND: Evidence regarding the association between illicit drug use (IDU) and Alzheimer's disease (AD) remains limited at the population level. This study aimed to investigate the relationship between IDU and AD and to explore the potential association with age at first drug use. METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES). AD was defined based on self-reported use of anti-dementia medications. IDU was defined as a history of cocaine, heroin, or methamphetamine use. Weighted logistic regression models were used to evaluate the association between IDU and AD. Subgroup and sensitivity analyses were conducted to assess the robustness of the findings. Restricted cubic spline (RCS) regression was applied to explore the potential nonlinear association between age at first IDU and AD. RESULTS: Among 31,876 participants, 5,857 (20%) reported a history of IDU. IDU was significantly associated with higher odds of AD in the adjustment model (OR = 1.73, 95% CI: 1.33-2.24, p < 0.001). Subgroup and sensitivity analyses yielded consistent results. RCS analysis revealed a nonlinear association between age at first IDU and AD (p for nonlinear = 0.016), with a U-shaped relationship indicating higher odds of AD among individuals who initiated drug use at younger ages. The inflection point was approximately 21 years. CONCLUSION: IDU and earlier initiation of drug use may be associated with higher odds of AD among US adults.