EXTRAPYRAMIDAL SIGNS AND PSYCHIATRIC-SYMPTOMS PREDICT FASTER COGNITIVE DECLINE IN ALZHEIMERS-DISEASE

Design: A cohort of patients was followed up longitudinally and the li kelihood of arriving at two cognitive end points was assessed using th e Cox proportional hazards model and eight explanatory variables. Sett ing: Subjects were chosen from patients examined for memory loss at tw o medical centers affiliated with the University of Southern Californi a, Los Angeles. Patients: The sample included 135 patients who met Nat ional Institute for Neurological and Communicative Disorders and Strok e-Alzheimer's Disease and Related Disorders Association criteria for p robable or definite Alzheimer's disease, had initial Mini-Mental State Examination (MMSE) scores of 14 or greater, and had been seen on at l east two occasions. Main Outcome Measures: The time to reach either of two end points, ie, MMSE score of 8 and a decline of six points on th e MMSE, was assessed. Results: After controlling for initial severity of dementia (eg, by dividing the sample into mild and moderate dementi a subgroups or by using the individually defined end point of a six-po int decline on the MMSE), the presence at baseline of extrapyramidal s igns (risk-hazard ratio, 10.34; 95% confidence interval, 2.76 to 38.68 ; P=.0005), agitation (risk-hazard ratio, 2.98; 95% confidence interva l, 1.35 to 6.61; P=.007), and hallucinations (risk-hazard ratio, 3.85; 95% confidence interval, 1.35 to 11; P=.01) predicted a shorter time to reach an end point. Conclusions: After controlling for initial seve rity of dementia, the presence of extrapyramidal signs and behavioral symptoms (agitation and hallucinations) significantly predict faster c ognitive decline. These findings may reflect the effects of neurolepti c medication, the presence of underlying diffuse Lewy body disease, or alterations in biogenic amine systems.