Concurrent Alcohol Use and the Relative Risk of Community-Acquired Pneumonia Associated With Anticholinergic and Non-Anticholinergic Neurocognitively Active Medication Receipt: A National Nested Case-Control Study Among US Veterans.

PURPOSE: Anticholinergic medications and alcohol each independently increase the risk of community-acquired pneumonia (CAP). Whether non-anticholinergic neurocognitively active medications also increase risk, and if alcohol modifies these associations, remains unclear. METHODS: We conducted a nested case-control study using Veterans Aging Cohort Study (VACS)-National data. We identified 157 185 incident CAP cases requiring hospitalization between 2010 and 2022. Cases were matched 1:5 to controls without CAP on demographics, cohort entry date, and dwell time in the underlying cohort study using incidence density (risk-set) sampling. CAP index date was hospital admission for cases and the equivalent follow-up date for controls. Primary exposures were receipt of anticholinergic and non-anticholinergic neurocognitively active medications within 90 days prior to the index date. Concurrent alcohol use was based on self-reported measures in the year prior to the index date. We estimated odds ratios (ORs) for associations between medication use, alcohol consumption, and CAP using logistic regression, adjusting for confounders. RESULTS: Median age was 69 years (interquartile range 62-78); 97% were male. Both medication types were independently associated with increased odds of CAP (anticholinergic: OR 1.62, 95% CI 1.57-1.67; non-anticholinergic: OR 1.61, 95% CI 1.57-1.66). Concurrent alcohol use modified these associations. For anticholinergics, ORs were 1.74 (95% CI 1.66-1.83) for at-risk consumption and 2.13 (95% CI 1.96-2.31) for hazardous/binge consumption. For non-anticholinergics, ORs were 1.74 (95% CI 1.67-1.81) and 2.20 (95% CI 2.06-2.34), respectively. CONCLUSIONS: Non-anticholinergic neurocognitively active medications showed similar CAP association patterns as anticholinergics, with the highest odds among those consuming alcohol. These findings highlight the need for caution when prescribing these medications and incorporating alcohol use into risk-benefit assessments.