Abstract: Background: Homelessness and housing instability disproportionately affect U.S. veterans with psychiatric disorders, HIV/AIDS, hepatitis C, and Alzheimer's Disease and Related Disorders (ADRD). We examined housing status and/or HIV/AIDS in relation to ADRD risk and evaluated hepatitis C, substance use, and mental health disorders as mediators and/or moderators of hypothesized relationships, among U.S. veterans ≥ 50 years of age seeking Department of Veterans Affairs (VA) healthcare services. Methods: A retrospective cohort study was conducted using linked VA Homeless Operations Management and Evaluation System and Corporate Data Warehouse databases (2017-2023) on 3,275,098 eligible veterans yielding 133,388 ADRD cases over 5 years of follow-up. Multivariable regression and causal mediation analyses were performed, controlling for demographic and clinical characteristics. Results: Taking stably housed veterans without HIV/AIDS as referent, ADRD risk was higher among veterans with homelessness/housing instability alone (adjusted hazard ratio [aHR]=1.67, 95% confidence interval [CI]: 1.63,1.72), lower among veterans with HIV/AIDS alone (aHR=0.65, 95% CI: 0.58,0.73), but similar to veterans with homelessness/housing instability and HIV/AIDS (aHR=1.01, 95% CI: 0.79,1.29). In adjusted models, hepatitis C and psychiatric disorders were positively related to homelessness/housing instability and ADRD risk, but negatively related to HIV/AIDS. Statistically significant mediation and/or moderation of hepatitis C and psychiatric disorders were observed, although <10% of total effects were explained by these characteristics, controlling for confounders. Conclusions: Among older veterans, ADRD diagnoses over 5 years were less among those with HIV/AIDS, but more among those with homelessness/housing instability, and these relationships were partly explained by hepatitis C and psychiatric disorders.