A Clinical Index to Predict Progression from Mild Cognitive Impairment to Dementia Due to Alzheimer's Disease

Background: Mild cognitive impairment is often a precursor to dementia due to Alzheimer's disease, but many patients with mild cognitive impairment never develop dementia. New diagnostic criteria may lead to more patients receiving a diagnosis of mild cognitive impairment. Objective: To develop a prediction index for the 3-year risk of progression from mild cognitive impairment to dementia relying only on information that can be readily obtained in most clinical settings. Design and Participants: 382 participants diagnosed with amnestic mild cognitive impairment enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI), a multi-site, longitudinal, observational study. Main Predictors Measures: Demographics, comorbid conditions, caregiver report of participant symptoms and function, and participant performance on individual items from basic neuropsychological scales. Main Outcome Measure: Progression to probable Alzheimer's disease. Key Results: Subjects had a mean (SD) age of 75 (7) years and 43% progressed to probable Alzheimer's disease within 3 years. Important independent predictors of progression included being female, resisting help, becoming upset when separated from caregiver, difficulty shopping alone, forgetting appointments, number of words recalled from a 10-word list, orientation and difficulty drawing a clock. The final point score could range from 0 to 16 (mean [SD]: 4.2 [2.9]). The optimism-corrected Harrell's c-statistic was 0.71(95% CI: 0.68-0.75). Fourteen percent of subjects with low risk scores (0-2 points, n=124) converted to probable Alzheimer's disease over 3 years, compared to 51% of those with moderate risk scores (3-8 points, n=223) and 91% of those with high risk scores (9-16 points, n=35). Conclusions: An index using factors that can be obtained in most clinical settings can predict progression from amnestic mild cognitive impairment to probable Alzheimer's disease and may help clinicians differentiate between mild cognitive impairment patients at low vs. high risk of progression.