INTRODUCTION: We evaluated a risk score comprising lifestyle, medical and demographic factors (ANU-ADRI), and a genetic risk score (GRS) as predictors of Mild Cognitive Impairment (MCI). METHODS: ANU-ADRI risk scores were computed for the baseline assessment of 2,078 participants from the PATH project. Participants were assessed for clinically diagnosed MCI/Dementia and psychometric test-based MCI (MCI-TB) at 12 years of follow-up. Multi-state models estimated the odds of transitioning from cognitively normal (CN) to MCI/Dementia and MCI-TB over 12 years according to baseline ANU-ADRI and GRS. RESULTS: Higher ANU-ADRI score predicted transitioning from CN to either MCI/Dementia and MCI-TB (Hazard ratio [HR] = 1.06, 95% CI:1.04-1.09; HR = 1.06, 95% CI: 1.03-1.09), and a reduced likelihood of cognitive recovery from MCI-TB to CN (HR = 0.69, 95% CI: 0.49-0.98). GRS was not associated with transition to MCI/Dementia, or MCI-TB. DISCUSSION: The ANU-ADRI may be used for population-level risk assessment and screening.