Modeling the influence of extrapyramidal signs on the progression of Alzheimer disease

Objective: To determine how the advent of extrapyramidal signs influences the progression of Alzheimer disease as measured by standard clinical measures. Design: We applied growth curve models to prospective data to characterize patients' cognitive and functional changes over time. To detect changes in disease course related to extrapyramidal signs, their onset was treated as a time-dependent covariate. Setting: Three research medical centers. Participants: Patients (n=217) with probable Alzheimer disease. Intervention: Patients were followed up semiannually for 5 years. Main Outcome Measures: Scores on the modified Mini-Mental State Examination and measures of basic and instrumental activities of daily living from the Blessed Dementia Rating Scale. Results: For basic and instrumental activities of daily living, disease course was more rapid once extrapyramidal signs developed. Decline in the modified Mini-Mental State Examination score was greater at the time the signs developed, but not at subsequent visits. Conclusions: The point at which extrapyramidal signs emerge is associated with measurable acceleration in the progression of Alzheimer disease. This may in part explain why extrapyramidal signs are associated with a poorer prognosis. The differential influence of extrapyramidal signs on cognitive and functional measures suggests that the pathological changes underlying these disease features may vary.