Abstract: PURPOSE: To examine whether lower medication adherence in individuals without documented dementia or cognitive impairment (DCI) is associated with subsequent clinically recognized DCI. METHODS: Retrospective cohort analysis that included veterans aged≥ 65 years, without documented DCI at baseline, without past or current prescription for DCI medications, with≥ 1 annual Veterans Affairs (VA) primary care visit, and with an ongoing VA prescription for any of the one or more of the following during a 3-year assessment period: lisinopril, metoprolol, omeprazole, or simvastatin. Adherence was estimated for each medication using proportion of days covered (PDC) and, secondarily, using medication possession ratio (MPR), with<0.8 classified as low adherence. Incident DCI was determined via ICD-9/ICD-10 diagnosis codes. RESULTS: Analyses included 794,569 unique veterans, separated in 4 medication cohorts (mean ages ranged from 75.6 [7.2] to 76.5 [7.2]), % male range was 98.2-98.6%). Between 16-21% of participants were categorized with low medication adherence by PDC. Over a 10-year follow-up period, incident DCI ranged from 17-18% in the low adherence group and 14-15% in the high adherence group. After multivariate adjustment, hazard for incident DCI in users of each of the four medications was significantly increased, about 20% greater among individuals with low adherence compared to those with high adherence. CONCLUSION: Among veterans without clinically recognized DCI, lower baseline medication adherence was associated with an increased risk for future clinically recognized DCI. Further studies should seek to disentangle whether low adherence is a risk factor for future DCI or an indicator of existing but not yet recognized DCI and whether this can inform clinical practice decisions.