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Yaakov Stern, PhD; Xinhua Liu, PhD; Marilyn Albert, PhD; Jason Brandt, PhD; Diane M. Jacobs, PhD; Caridad Del Castillo-Castaneda; Karen Marder, MD, MPH; Karen Bell, MD; Mary Sano, PhD; Fred Bylsma, PhD

Arch Neurol. 1996;53(11):1121-1126.

Abstract
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.

Author Affiliations
From the Departments of Neurology (Drs Stern, Jacobs, Marder, Bell, and Sano) and Psychiatry (Dr Stern) and the Gertrude H. Sergievsky Center (Drs Stern, Liu, Jacobs, Marder, and Sano, and Mr Del Castillo-Castaneda), Columbia University College of Physicians and Surgeons, New York, NY; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Md (Drs Brandt and Bylsma); and Departments of Psychiatry and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (Dr Albert).

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