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To develop a practical informant-based screening tool that reliably identifies patients with mild cognitive impairment (MCI) and dementia, we analyzed data from a sample of patients and normal controls seen in a memory clinic. All patients were evaluated with the Clinical Dementia Rating scale. Individual Clinical Dementia Rating responses were dichotomized and entered into a forward stepwise multivariable logistic regression model. Four independent predictors of MCI and dementia thus identified were combined into a prediction rule that was validated in a separate cohort drawn from the same clinic. Using a cut point of 2 or more positive responses to the 4 questions, the final prediction rule had sensitivity of 95% (95% confidence interval (CI): 92-97%) for MCI or dementia, and a specificity of 91% (95% CI: 86-95%). When applied to the validation cohort, the sensitivity for MCI or dementia was 96% (95% CI: 94-98%), and the specificity was 96% (95% CI: 92-98%). Using both cohorts, the positive likelihood ratio for MCI or dementia was 15.6 (95% CI: 14.0-17.3) and the negative likelihood ratio was 0.05 (95% CI: 0.04-0.07). This tool has the potential to identify patients who warrant further cognitive evaluation in busy outpatient or emergency department settings.