Extrapyramidal signs and psychiatric symptoms predict faster cognitive decline in Alzheimer's disease.
OBJECTIVE
To identify clinical predictors of cognitive decline in Alzheimer's disease.


METHODS
A cohort of patients was followed up longitudinally and the likelihood of arriving at two cognitive end points was assessed using the Cox proportional hazards model and eight explanatory variables.


METHODS
Subjects were chosen from patients examined for memory loss at two medical centers affiliated with the University of Southern California, Los Angeles.


METHODS
The sample included 135 patients who met National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable or definite Alzheimer's disease, had initial Mini-Mental State Examination (MMSE) scores of 14 or greater, and had been seen on at least two occasions.


METHODS
The time to reach either of two end points, ie, MMSE score of 8 and a decline of six points on the MMSE, was assessed.


RESULTS
After controlling for initial severity of dementia (eg, by dividing the sample into mild and moderate dementia subgroups or by using the individually defined end point of a six-point decline on the MMSE), the presence at baseline of extrapyramidal signs (risk-hazard ratio, 10.34; 95% confidence interval, 2.76 to 38.68; P = .0005), agitation (risk-hazard ratio, 2.98; 95% confidence interval, 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 severity of dementia, the presence of extrapyramidal signs and behavioral symptoms (agitation and hallucinations) significantly predict faster cognitive decline. These findings may reflect the effects of neuroleptic medication, the presence of underlying diffuse Lewy body disease, or alterations in biogenic amine systems.
Department of Neurology, University of Southern California School of Medicine, Los Angeles.
H C
HC
Chui
S A
SA
Lyness
E
E
Sobel
L S
LS
Schneider
D000368:Aged; D000544:Alzheimer Disease / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology / Q000523:psychology*; D001480:Basal Ganglia Diseases / Q000209:etiology*; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology; D003702:Delusions / Q000209:etiology; D005260:Female; D006212:Hallucinations / Q000209:etiology; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D011595:Psychomotor Agitation