Predictors of progression to severe Alzheimer's disease in an incidence sample

Background: Little is known about factors influencing time to severe Alzheimer's disease (AD). Methods: Incident cases of AD in the Cache County Memory Study were identified. Severe AD was defined as Mini-Mental State Examination score of ≤10 or Clinical Dementia Rating Scale score of 3; cases with either Mini-Mental State Examination score of ≥16 or Clinical Dementia Rating <2 were not categorized as severe AD. Kaplan-Meier, log-rank tests, and Cox analyses were used to identify demographic, clinical, and genetic correlates of time to progression to severe AD. Results: Sixty-eight of 335 cases of incident AD developed severe dementia. In bivariate analyses, female gender, less than high school education, at least one clinically significant Neuropsychiatric Inventory domain at baseline, and the youngest and oldest ages exhibited shorter time to severe AD. In competing risk analysis, subjects with mild or at least one clinically significant Neuropsychiatric Inventory domain score, and subjects with worse health were more likely to progress to severe dementia or death. Conclusions: Demographic and clinical variables predict progression to severe AD. Further study should examine whether these relationships are causal or correlational.