Utility of extrapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission, and death in Alzheimer’s disease: Prospective analyses from the predictors study

Objective To examine whether either extrapyramidal signs or psychotic features are associated with more rapid progression of Alzheimer’s disease. Background It has been unclear whether extrapyramidal signs and psychosis are predictors of faster course or are simply late signs. Methods Two hundred thirty-six patients with mild Alzheimer’s disease were recruited in three cities and followed semiannually.. Results Using Cox proportional hazards models that adjusted for age, sex, disease severity, and estimated duration of illness at study entry, the presence of extrapyramidal signs at entry was associated with higher relative risk (RR) of reaching moderate cognitive (RR = 2.35, 95% CI = 1.12 to 4.92) or functional (RR = 2.31, 95% CI = 1.37 to 3.90) severity, nursing home entry (RR = 2.51, 95% CI = 1.32 to 4.76), or death (RR = 3.04, 95% CI = 1.31 to 7.05). Psychosis predicted only the functional end point (RR = 1.85, 95% CI = 1.18 to 2.90). Using regression models, modified Mini-Mental State scores declined 1.30 points (95% CI = 0.16 to 2.44) per 6-month interval, more among patients with than those without extrapyramidal signs; patients with psychosis declined 1.15 (95% CI = 0.52 to 1.77) more mMMS points per interval. Conclusions This study confirms extrapyramidal signs and psychosis as robust predictors of disease end points and rapid progression in Alzheimer’s disease.